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Global prevalence of allergic diseases has been on the rise for the last 30 years. In Canada, this upward trend in allergic diseases has resulted in over 3 million Canadians being affected by allergic asthma. Allergic asthma is triggered by inhalation of environmental allergens resulting in bronchial constriction and inflammation, which leads to clinical symptoms such as wheezing, coughing and difficulty breathing. Asthmatic airway inflammation is initiated by the release of inflammatory mediators (-eg- histamine) released by granulocytic cells (-eg- mast cells and basophils). However, immunoglobulin E (IgE) antibody is also necessary for the initiation of the allergic cascade, and IgE is produced and released exclusively by memory B cells and plasma cells. Allergen crosslinking of IgE:FcεRI complexes on the surface of mast cells and basophils causes degranulation of pro-inflammatory mediators. Acute allergen exposure has also been shown to increase IgE levels in the airways of patients diagnosed with allergic asthma; however, more studies are needed to better understand local airway inflammation. Our group's work, in accordance with the literature, has shown an increase of IgE in the airways of subjects with mild allergic asthma following allergen inhalation challenge. Although regulatory B cells (Bregs) have been shown to modulate IgE-mediated inflammatory processes in allergic asthma pathogenesis, particularly in mouse models of allergic airway disease, the levels and function of these IgE+ B cells and Bregs remain to be elucidated in human models of asthma. The overall objective for this dissertation was to investigate the biology of B cells in allergic asthma pathogenesis, specifically investigating the frequency of IgE+ B cells and Bregs in allergic asthma, and the kinetics of these cells after allergen exposure. First, we characterized IgE+ B cells in the blood and sputum of allergic asthmatics and healthy controls with and without allergies (Chapter 2). We showed that IgE+ B cell levels were higher in sputum, but not blood, of allergic asthmatics compared to controls. We further demonstrated that these findings were consistent across airway IgE+ B cell subsets, which include IgE+ memory B cells and IgE+ plasma cells. Additionally, IgE+ B cells in sputum positively correlated with sputum eosinophils, total IgE and B cell activating factor (BAFF) measured in sputum fluid phase. These findings highlight the association of airway IgE+ B cells with allergic asthma, and suggest that local IgE+ B cell functions contribute to the pathogenesis of asthma. Second, we measured the trafficking of IgE+ B cells in periphery (blood, bone marrow and tonsil) and locally (sputum) in allergic asthmatics following whole lung allergen challenge (Chapter 3). IgE+ B cells only increased in the airways of allergic asthmatics following allergen inhalation challenge; there were no allergen-induced changes in IgE+ B cell levels in blood, bone marrow and tonsil. In addition, we showed allergen-induced increases in BAFF and total IgE, but not allergen-specific IgE in sputum fluid phase. Taken together, chapters 2 and 3 show that allergic asthmatics have elevated levels of IgE+ B cells in the airways, that can be further increased after allergen exposure. Therefore, local B cell production of IgE in the lungs may be an important source of IgE for initiation of acute inflammatory responses in allergic airways. Third, we evaluated the levels of Bregs in allergic asthmatics compared to controls, and examined the kinetics, function and distribution (bone marrow, blood and sputum) of Bregs following allergen inhalation challenge (Chapter 4). We showed that Bregs were 2-fold lower in the blood of allergic asthmatics compared to controls, highlighting a possible dysregulation of this regulatory cell type in allergic asthmatics, which may contribute to disease pathology. Furthermore, after whole lung allergen challenge Bregs decreased in the bone marrow with a co-incident increase in the blood and sputum of allergic asthmatics. This pattern reflects potential trafficking of these cells from bone marrow to the airways after exposure to allergic stimuli. Lastly, we stimulated CD19+ B cells purified from blood of allergic asthmatic with IL-4 in vitro. IL-4 is a type 2 cytokine known to isotype-switch B cells to IgE+ B cells, as well as differentiates naïve T cells into Th2 cells, thus propagating the allergic cascade. We found that IL-4 promoted higher proportions of IL-10+ and FoxP3+ Bregs, which demonstrates that Bregs may have a role in dampening IgE-mediated inflammation in a type 2 environment. However, further functional studies are warranted. Taken together, the findings of this dissertation highlight the local compartmental changes in IgE+ B cells and Bregs following allergen challenge of allergic airways. Better understanding the temporal and compartmental shifts in B cell subpopulations, particularly IgE+ B cells and Bregs, may aid in future development of therapeutics. / Thesis / Doctor of Philosophy (PhD)

Yes / The fabrication of osmium nanoclusters from single atoms has been studied in real-time on B-doped and B-free graphitic surfaces. The dynamics of nucleation on both surfaces are identified, captured, and reported. The nucleation is ca. 2× faster on B-doped surface compared to the B-free surface (38 pm min−1versus 18 pm min−1), suggesting osmium–boron interactions within the nanomaterials.

Yes / Coronavirus is the most dangerous virus in the world wide and it can easy spread between people, animals and plants because it is existing on one strand of RNA (Ribonucleic Acid) and it can duplicate faster than any virus. The source of coronavirus is still unknown, but some sources said that it came from seafood market and other sources said that it came from bat and snakes. It starts in Wuhan; China and every day the fatality increases. The symptoms are like a SARS-CoV (acute respiratory syndrome coronavirus)) and MERS-CoV (Middle East Respiratory Syndrome Coronavirus). By using nucleotide sequence of coronavirus from NCBI (National Center for Biotechnology Information) and some programs that ran on Matlab, the results show that there are some differences and similarities between coronavirus and other viruses such as Ebola, Flu-b, Hepatitis B, HIV and Zika especially for DEBs (distinct excluded blocks) program that shows at 5bp (base pair) there is a common with slightly difference between coronavirus “cgggg” and Ebola virus “cgtgg”. The aim from this study is to find a way to help doctors and scientists to stop spreading the coronavirus or to destroy it.

Phase transformation behavior, micro structural development, mechanical and tribological properties of electroless Ni-B coating was characterized using different characterization techniques. As deposited electroless Ni-B coating containing 94 wt. % of NI and 6 wt. % of B is amorphous. It crystallizes via two exothermic reactions one at 3000C and another at 430˚C. It has been observed that there is also slow evolution of the heat in between this two exothermic reactions. XRD studies display that as deposited coating undergoes multi-stage crystallization events. At the first exothermic peak NI3B phases crystallizes, in between two a phase mixture of Ni and Ni3B and at the second exothermic peak NI2B + Ni3B crystallizes. Evolution of the free Ni in the complete crystalline coating is not predicted by the equilibrium phase diagram of the Ni-B system. Microscopic observation of the as deposited coating displays a novel compositionally modulated microstructure comprises of different length scales ranging from micrometer to nanometer level. In situ TEM study along with composition analysis were carried out in order to track the crystallization pathway and microstructural development. This kind of composition fluctuation of the coating is intrinsic to the deposition process. In best of our knowledge this kind of microstructure is the first time reported example of phase separation in a binary metal-metalloid system without spinoidal decomposition. Effect of this kind of microstructure and phase evolution on the mechanical and tribological properties of the coating is very profound. Increase in the nanocrystalline borides content of the coating increases the hardness value of the coating as well as improved tribological properties of the coating. In the low load regime (5 N and less) wear resistance of the coating is provided by the oxide layer formed on the wear track by preventing the direct contact between the coating and counterface. Local temperature rise due to friction and nancrystalline nature of the coating enhances the tendency of oxide layer formation. Characterization of the oxide layer was carried out using SEM, EPMA, Nanoindenation and Raman Spectroscopy. Whereas in case high load regime (above 5 N) this oxide layer breaks off and direct contact between the coating and counterface is established. This increases the wear rate of the coating. Material is removed from the coating through subsurface crack formation and propagation by low cycle fatigue mechanism. Effect of amorphous phase and free Ni on the tribological properties of the coating is detrimental by promoting a strong adhesion between the coating and steel counter face, whereas nanocrystalline borides shows opposite effect. A nano tribological studies using lateral force microscopy shows that nanocrystalline borides decreases the coefficient of friction of the coating. Phase evolution and microstructural characterization also shows that above 450˚C there is a significant diffusion of the boron from the coating to the steel substrate. This restrict the high temperature tribological studies of the coating up to a temperature range of 450˚C. Wear data along with worn track characterization demonstrate the fact that above 100˚C even in low load regime wear rate is very high. Wear of the coating is mainly governed by the plastic deformation of the coating and breakage of the protective oxide layer. Analytical calculation as well experimental observation shows that during the time of wear the temperature at the local contact region reaches a very high value even up to 1100˚C. This may soften the coating and causes the wear though plastic deformation of the coating.

I denna uppsats utreds dels om en Internetleverantör har ett medverkansansvar enligt BrB, när den i sin roll som mellanhand, via tjänsten Internetuppkoppling ger sina kunder tillgång till tjänster/webbsidor som används för att begå immaterialrättsintrång enligt gällande rätt, och dels huruvida det svenska rättsläget är förenligt med de direktiv som har utfärdats av EU på området.  I uppsatsen undersöks möjligheten till vitesförbud enligt 53 b § URL, i förhållande till lagstift-ning, förarbeten och EU-direktiv. Vidare undersöks både svensk praxis på området och ett för-handsavgörande från EU-domstolen. I ett försök att förstå gällande svensk rätt görs även en kortare jämförelse med dansk rätt, och dess domstolars möjlighet att utfärda vitesförbud mot Internetleverantörer. Utifrån bestämmelsen om vitesförbud i 53 b § URL torde det inte vara möjligt för en svensk domstol att utfärda ett vitesförbud mot en Internetleverantör som enbart tillhandahåller tjänsten Internetuppkoppling åt sina kunder. Det framkommer av de svenska förarbetena att det, för att utfärda ett sådant förbud, krävs både vetskap om intrången samt ett avtalsliknande förhållande mellan Internetleverantören och intrångsgöraren.  Vi kommer slutligen fram till att även om artikel 8.3 i Infosoc-direktivet kan anses ha imple-menterats på rätt sätt enligt dess ordalydelse är tillämpningen av 53 b § URL, i enlighet med förarbetena, i dagsläget sådan att den torde strida mot syftet med artikel 8.3. Det anser vi bör leda till att en direktivkonform tolkning av artikeln inte bara kan, utan även ska tillämpas av svensk domstol. Således kan, enligt oss, en Internetleverantör, genom att förbjudas medverka till intrång, åläggas att blockera sina kunders tillgång till tjänster/webbsidor som används för att begå immaterialrättsintrång enligt 53 b § URL även i de fall där leverantörerna endast med-verkar genom att tillhandahålla tjänsten Internetuppkoppling.

En premier lieu, en utilisant des inhibiteurs pharmacologiques du NF-[kappa]B, nous avons constaté que l'inhibition du facteur de transcription NF-[kappa]B chez ces cellules diminue de beaucoup l'expression génique et la sécrétion de diverses cytokines et chimiokines (TNF-[alpha], IL-8 ou CXCL8, Mip-1[alpha]/[bêta] induites par des stimuli tels que TNF-[alpha] ou LPS. Nous montrons ensuite que le complexe IKK (IKK[alpha], IKK[bêta], et IKK[gamma]) est aussi partiellement localisé dans le noyau, alors que les kinases reliées à IKK (IKK[epsilon] et TBK-1) sont cytoplasmiques; la kinase NIK, quant à elle, est strictement nucléaire. Suite à une activation des neutrophiles, IKK[bêta] et IKK[gamma] deviennent transitoirement phosphorylées dans le cytoplasme et le noyau, alors qu'IKK[alpha] disparaît temporairement de ces deux compartiments cellulaires d'une manière qui semble dépendante de IKK[bêta]. Ces réponses s'accompagnent, dans les deux compartiments, de la dégradation d'I[kappa]B[alpha] et de la phosphorylation du RelA sur la sérine 536. Bien que les deux protéines puissent être des substrats de IKK, l'inhibition de ce dernier empêche la dégradation d'I[kappa]B[alpha], tandis que le niveau de phosphorylation du RelA est essentiellement inchangé. Nous apportons enfin une preuve que des isoformes de IKK nucléaires s'associent à la chromatine suivant l'activation des neutrophiles, ce qui suggère un rôle potentiel dans la régulation de gènes. Deuxièmement, nous rapportons que les neutrophiles expriment la MAP3K, TAK1, ainsi que ses partenaires associés, TAB1/2, dans le cytoplasme et le noyau. La kinase TAK1 est associée de façon constitutive aux protéines TAB1 et TAB2, ainsi qu'au complexe IKK[alpha]/[bêta] dans les neutrophiles au repos. Le niveau d'interaction de ces complexes demeure inchangé suite au traitement des neutrophiles avec le TNF-[alpha] ou le LPS. La kinase TAK1 devient rapidement et transitoirement activée suite à une stimulation des cellules avec le TNF-[alpha] ou le LPS. L'inhibition de l'activité kinase de TAK1 avec un inhibiteur hautement sélectif (5z-7-oxozeaenol) a empêché la phosphorylation d'IKK[alpha]/[bêta], de RelA, et la dégradation de I[kappa]B[alpha] dans les fractions cytoplasmiques et nucléaires, ainsi que la liaison à l'ADN du NF-[kappa]B dans des neutrophiles activés.En conséquence, l'expression et la sécrétion de cytokines inflammatoires induites par le TNF-[alpha] ou le LPS ont été profondément altérées suivant une inhibition de TAK1.En revanche, la phosphorylation de IKK[gamma] induite par le LPS n'a pas été affectée par l'inhibition de TAK1. Finalement, nos résultats indiquent que l'activation du NF-[kappa]B et les réponses cellulaires dépendantes du NF-[kappa]B sont indépendantes des ROS endogènes dans les neutrophiles humains primaires ou dans la lignée promyélocytaire PLB-985, qui peut être différenciée en granulocytes et se comporte comme les neutrophiles. Parallèlement, nous avons optimisé les conditions de transfection des PLB-985 différenciées, ce qui nous a permis de montrer pour la première fois l'activation de promoteurs [kappa]B-dépendants chez des granulocytes humains. Ces travaux rendent par ailleurs possibles les études portant sur l'activation des promoteurs chez les granulocytes. Dans leur ensemble, ces observations démontrent l'importance du NF-[kappa]B dans la génération inductible de cytokines et chimiokines par les neutrophiles. Il s'agit de la première étude qui montre la présence et l'activation (phosphorylation) du complexe IKK et la phosphorylation des protéines NF-[kappa]B/Rel dans les neutrophiles humains. Plus important encore, nos résultats dévoilent un mode d'activation de la cascade de signalisation IKK/I[kappa]B/NF-[kappa]B dans le noyau de cellules primaires. Nos données établissent également le rôle central de TAK1 dans le contrôle de la cascade de signalisation IKK/I[kappa]B/NF-[kappa]B cytoplasmique et nucléaire dans les neutrophiles primaires humains, ce qui pourrait représenter une cible prometteuse pour une intervention thérapeutique considérant le rôle critique des neutrophiles dans plusieurs conditions inflammatoires.

L'hypothèse d'une quatrième famille de fermions –les particules de matière décrites au sein du Modèle Standard (MS) de la physique des particules– est un des plus simples modèles de nouvelle physique encore non exclu et accessible au démarrage du LHC – le plus puissant collisionneur hadronique au monde depuis 2009. Cette thèse s'intéresse à la production d'une paire de quarks t' se désintégrant chacun via Wb. La recherche se focalise sur le domaine des très hautes masses, où la production peut être distinguée de la production de bruit de fond d'une paire de quark top en exploitant la cinématique des produits de désintégration des collisions p-p produites au centre du détecteur ATLAS. Nous présentons une stratégie originale exploitant la collimation des produits de la désintégration des bosons W de grande impulsion transverse, permettant leur reconstruction explicite. L'analyse s'appuie sur un travail de mise en oeuvre des algorithmes d'identification des jets résultants de la fragmentation des quarks de saveur b. L'étiquetage-b permet à l'expérience ATLAS d'améliorer la (re)découverte du MS, et la sensibilité à la nouvelle physique. Il sera ainsi d'une grande importance pour les futures années d'opération du LHC, raison pour laquelle nous présentons une étude de prospective de ses performances attendues avec l'extension du détecteur à pixels d'ATLAS dénommée IBL. Notre recherche de quark t' a permis d'établir une limite inférieure à la masse du quark t' de 656 GeV à partir des 4.7 fb^−1 de données 7 TeV collectées en 2011, ce qui est la meilleure limite à ce jour en recherche directe, avec également une interprétation dans le cadre du modèle de quarks dits vecteurs. / The hypothesis of a fourth generation of fermions – the matter particles described in the Standard Model (SM) of particle physics – is one of the simplest model of new physics still not excluded and accessible at the start of the Large Hadron Collider (LHC) – the world most powerful hadron collider since 2009. We search for the pair production of up-type t' quarks decaying to a W boson and a b-quark. The search is optimized for the high quark mass regime, for which the production can be distinguished from the top background by exploiting kinematic features of the decay products arising from the proton-proton collisions occurring at the center of the ATLAS detector. We present a novel search strategy reconstructing explicitly very high-pT W bosons from their collimated decay products. The analysis benefits from the commissioning of algorithms intended to identify jets stemming from the fragmentation of b-quarks. These algorithms are based on the precise reconstruction of the trajectory of charged particles, vertices of primary interaction and secondary vertices in jets. The b-tagging ability allows for ATLAS to improve the (re)discovery of the SM, and the sensibility to new physics. It will hence play an important role in the future of the LHC, the reason why we study the expected performance with an upgrade of the ATLAS pixel detector, called IBL and currently under construction. Our search of t' quark, using 4.7 fb^−1 of the 7 TeV data collected in 2011, has resulted in the world most stringent limit, excluding t' masses below 656 GeV, with also an interpretation in the framework of vector-like quarks.

A terapia endodôntica visa o selamento biológico do complexo sistema apical, contribuindo para isso, as substâncias usadas no tratamento e a resposta imune do paciente. A LILT tem mostrado atividade antiinflamatória, favorecendo o processo reparacional. Sendo assim, este trabalho objetivou analisar o efeito da LILT na atividade secretória de macrófagos, previamente ativados por IFN-? e LPS de E.coli, e estimulados por substâncias liberadas de três tipos de cimentos endodônticos, um a base de óxido de zinco e eugenol, outro a base de hidróxido de cálcio e um terceiro resinoso. A citotoxicidade dessas substâncias foi avaliada usando a técnica de análise do MTT. Macrófagos ativados foram estimulados por essas substâncias ou não (controle) e então, irradiados ou não (controle) e a secreção de proteínas próinflamatórias (interleucina-1 b, fator de necrose tumoral-a e metaloproteinase da matriz-1) foram analisadas pelo teste ELISA. As irradiações foram realizadas com um laser GaAlAs (780 nm, 70 mW, ponta da fibra de 4 mm2, 1.67 seg, 3 J/cm2). Foram usadas duas aplicações de irradiação com intervalo de 6 h. Os dados obtidos foram tratados por Análise de Variância, quando de distribuição normal, ou teste de Friedman, quando de distribuição não normal, com nível de significância de 5 % (p = 0,05). A viabilidade dos controles e células tratados pelos cimentos endodônticos foi similar. Produção de IL-1 b e TNF-a foram observadas. Houve alta produção de MMP-1. Entretanto, sem diferenças estatísticas entre os grupos experimentais. Os grupos irradiados apresentaram resultados similares aos não irradiados. Substâncias liberadas pelos cimentos endodônticos testados não se mostraram citotóxicas nas condições deste experimento. Essas substâncias, bem como a LILT, no parâmetro utilizado, não causam alteração na atividade de secreção de MMP-1, IL-1 b e TNF-a por macrófagos ativados. / The endodontic therapy seeks the dental root canal biological sealing, depending on substances used in this process and patient’s defense immune factors. LILT has shown an anti-inflammatory activity, improving the periapical repair process. This in vitro study aimed to analyze the effect of LILT at the secretory activity of macrophages previously activated by interferon-gamma and lypopolisaccharide from E.coli, and stimulated by substances leached from three endodontic sealers (zinc oxide-eugenol based, resinous and calcium hydroxide-based). Cytotoxicity of these substances was assessed by the MTT test. Activated macrophages were stimulated by the substances or not (control) and then, irradiated or not (control) and the secretion of pro-inflammatory proteins (interleukin-1 b, tumor necrosis factor-a and matrix metalloproteinase-1) was analyzed by ELISA test. The LILT was performed using a GaAlAs laser (780 nm, 70 mW, focal spot of 4.0 mm2, 1.67 sec, 3 J/cm2). Two irradiations with 6 h-intervals were done. The data was compared by either ANOVA test or Friedman’s test. The cell viabilities of controls and cells treated by the sealers were similar. Production of IL -1 b and TNF-a were observed. There was a high production of MMP-1. However, statistical differences were not observed amongst the groups. The irradiated groups presented results similar to those of non irradiated groups. Substances leached from the endodontic sealers are non cytotoxic at these experiments conditions . These substances, as well as the LILT, at the parameter used, were not able to change the secretion of MMP-1, IL-1 b e TNF-a by activated macrophages.

Ho Kar Fai, William. / Thesis submitted in: July 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 121-129). / Abstracts in English and Chinese. / Abstract --- p.I / Acknowledgement --- p.V / Table of Contents --- p.VI / Abbreviations --- p.VIII / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- The recent situation of hepatitis B infection and HBV-induced HCC in Hong Kong / Chapter 1.2 --- Natural history of HBV infection in human / Chapter 1.3 --- The genomic organization of HBV / Chapter 1.4 --- Potential oncogenic mechanism of HBV-induced hepatocarcinogenesis / Chapter 1.5 --- Aim of the present study / Chapter Chapter 2 --- Materials and methods --- p.16 / Chapter 2.1 --- Transformation in E.coli for subtracted normal-counterpart library / Chapter 2.2 --- PCR amplification of subtracted clones / Chapter 2.3 --- Sequencing of subtracted clones with dye-terminator cycle sequencing technology / Chapter 2.4 --- Sequence analysis and database construction / Chapter 2.5 --- Molecular cloning and characterization of novel gene / Chapter 2.6 --- In silico structural and functional analysis of Z313 / Chapter 2.7 --- Cloning and sequencing analysis of zinc finger protein 313 (Z313) / Chapter 2.7.1 --- PCR amplification of target gene -Z313 / Chapter 2.7.2 --- Mini-preparation of plasmid DNA / Chapter 2.7.3 --- Cycle sequencing of cloned cDNA -Z313 with dye-primer technology / Chapter 2.8 --- Multiple Tissue Northern (MTN) blot hybridisation / Chapter 2.9 --- RT-PCR analysis of Z313 / Chapter 2.10 --- Subcellular localization study of Z313 by Green Fluorescent Protein (GFP) / Chapter 2.10.1 --- Directional cloning of Z313 into pEGFP-Cl / Chapter 2.10.2 --- Mini-preparation of plasmid DNA / Chapter 2.10.3 --- Transient transfection of plasmids in different cell lines / Chapter 2.10.4 --- Microscope observation of GFP transfected cells / Chapter Chapter 3 --- Results --- p.49 / Chapter 3.1 --- PCR selection of subtracted clones for sequencing analysis / Chapter 3.2 --- Partial sequencing of selected subtracted clones / Chapter 3.3 --- DNA homology searching using program - BLASTN / Chapter 3.4 --- Catalogue of the 467 ESTs from the subtracted normal-counterpart library / Chapter 3.5 --- Classification and frequency of the subtracted normal-counterpart cDNA clones / Chapter 3.6 --- Identification of putative differentially expressed genes in HCC surrounding normal liver / Chapter 3.7 --- Categorization of ESTs exclusively appeared in the subtracted normal- counterpart library / Chapter 3.8 --- In silico structural and functional analysis of zinc finger protein313 (Z313) / Chapter 3.9 --- Molecular cloning of zinc finger protein 313 (Z313) / Chapter 3.10 --- Northern analysis of zinc finger protein 313 (Z313) / Chapter 3.11 --- RT-PCR analysis of zinc finger protein 313 (Z313) / Chapter 3.12 --- Subcellular localization study of zinc finger protein 313 (Z313) / Chapter Chapter 4 --- Discussion --- p.104 / Chapter 4.1 --- EST analysis on the subtracted normal-counterpart cDNA clones / Chapter 4.1.1 --- Characterization of ESTs generated from the subtracted normal-counterpart library / Chapter 4.1.2 --- Putative differentially expressed genes in HCC surrounding normal liver related to hepatocellular carcinoma / Chapter 4.2 --- Molecular cloning and characterization of zinc finger protein313 (Z313) / Chapter 4.3 --- Future aspects / References --- p.121