Title: Analysis of J/Psi + photon production in proton-proton collisions on ATLAS at LHC Author: Bc. Zuzana Vidláková Department: Institute of particle and nuclear physics Supervisor: prom. fyz. Václav Vrba, CSc. (Academy of Sciences of the Czech Republic) Abstract: The subject of this thesis is physics connected to quarkonia and their studies at the ATLAS detector situated at LHC in CERN, Geneva. In this thesis, following topics are cov- ered: ATLAS detector, history of physics connected to quarkonia, production mechanisms of quarkonia, software used at CERN for data analysis and cross-section measurement of J/Psi + photon continuum. The analysis was done on behalf of the B-physics working group at ATLAS. Keywords: CERN, LHC, ATLAS, B-fyzika, quarkonia

Dentre os diversos fatores responsáveis pela instabilidade química das vitaminas nos alimentos, a exposição à radiação luminosa é determinante, principalmente em alimentos contendo vitamina B2. O presente trabalho investigou a degradação fotossensibilizada das vitaminas do complexo B (ácido fólico, piridoxal, biotina e niacina) por flavinas. O piridoxal-5\'-fosfato (PLP) mostrou-se reativo frente aos estados singleto e tripleto excitado das flavinas com constante de desativação de 1,03 1011 L mol-1 s-1 para o estado singleto, valor este superior ao valor esperado para reações bimoleculares controladas por difusão em meio aquoso. Foi observada uma dependência significativa da constante de velocidade de desativação do estado singleto excitado com a temperatura, onde o aumento da temperatura proporciona um decréscimo da constante de velocidade sugerindo a existência de um complexo [FMN...PLP] no estado fundamental o qual foi confirmado por espectroscopia de fluorescência resolvida no tempo. O PLP mostrou-se reativo frente ao estado tripleto excitado da FMN com constante de velocidade de 3kq = 3,0 108 L mol-1 s-1 em meio de tampão fosfato pH 6,4 ou em meio de óxido de deutério a 25 °C. Não foi observada diferença significativa entre as constantes de desativação do estado tripleto excitado em meio aquoso e de óxido de deutério o que corrobora com um processo direto de transferência de elétrons do PLP para a 3FMN* ao invés de um processo de transferência de átomo de hidrogênio. As vitaminas (biotina e niacina) mostraram-se não reativas frente aos estados singleto e tripleto excitados da vitamina B2 o que pode ser atribuído aos altos potenciais de oxidação, Eo > 2 V vs. NHE, observados para estas vitaminas em meio aquoso. A voltametria cíclica do PLP apresentou um processo anódico e irreversível (E= 1,07 V vs. NHE), controlada cineticamente por transferência de elétrons heterogênea do PLP para o eletrodo. O rendimento quântico de fotodegradação do PLP em meio aquoso e aerado é 2,5 vezes superior ao encontrado para a reação em meio anaeróbico, o que sugere a participação do íon superóxido no processo global de degradação do PLP. O ácido fólico demonstrou-se igualmente reativo frente ao estado tripleto excitado das flavinas (3kq= 4,8 108 L·mol-1 s-1 e Φ = 0,26 (meio aerado) e Φ = 0,32 (meio anaeróbico)) e a sua complexação pela β-LG (Φ = 0,032 (meio aerado) e Φ = 0,055 (meio anaeróbico)) uma eficiente abordagem na proteção desta vitamina frente a fotodegradação sensibilizada por flavinas. / Among several factors responsible for the chemical instability of vitamins in food, exposure to light radiation is decisive, especially in supplemented or fortified food with vitamin B2. This study investigated the photosensitized degradation of B-vitamins (folic acid, pyridoxal, biotin and niacin) by flavins. The pyridoxal-5\'-phosphate (PLP) reacted with singlet and triplet excited states of flavins with rate constant for quenching of 1kq = 1,03 1011 L mol-1 s-1 for the singlet state, this value is higher than expected value of bimolecular reactions controlled by diffusion in an aqueous solvent. A significant dependence was observed for the rate constant for deactivation of singlet excited state with temperature, the increase of the temperature leads to a decrease of the rate constant suggesting the existence of a complex [FMN...PLP] in ground state confirmed by time resolved fluorescence spectroscopy. PLP reacted with FMN triplet excited state with rate constant 3kq = 2,96 108 L mol-1 s-1 in phosphate buffer pH 6,4 or deuterium oxide at 25 °C. There was no significant difference between the rate constant of deactivation of the triplet-excited of FMN in aqueous solution or deuterium oxide which confirms a direct process of electron transfer to PLP for 3FMN* rather than a process of transfer of hydrogen atom. Biotin and niacin unreacted with singlet and triplet excited states of vitamin B2 which can be attributed to high oxidation potentials, Eo > 2 V vs. NHE, observed for this vitamins in aqueous solution. The cyclic voltammetry of PLP had an irreversible anodic oxidation process (E = 1.07 V vs. NHE) kinetically controlled by heterogeneous electron transfer from PLP to the electrode. The quantum yield of photodegradation of PLP in aerobic condition is 2.5 times higher than that found for the reaction in anaerobic condition, which suggests the of participation of superoxide ion in the PLP global degradation process. Folic acid demonstrated reactive with triplet excited state of flavins (3kq= 4,8 108 L·mol-1 s-1 and Φ = 0,26 (aerobic condition) and Φ = 0,32 (anaerobic condition)) and the complexation with β-LG (Φ = 0,032 (aerobic condition) and Φ = 0,055 anaerobic condition)) an efficient approach in protecting the vitamin against photodegradation sensitized by flavins.

O processo HDDR tem-se mostrado de grande interesse para a produção de ímãs à base de terras raras e polímeros. Apresenta vantagens comerciais quando comparado com os ímãs sinterizados convencionais, por exemplo, pela facilidade e menores custos de produção. Com o desenvolvimento de pós anisotrópicos, utilizando praseodímio, as expectativas em relação a este processo aumentam e, também, a necessidade de se estudar novas composições e adições. Neste trabalho, foram investigadas as propriedades magnéticas de ímãs moldados com resina, preparados com pós de ligas magnéticas de PrFeB, usando o processo HDDR. A liga magnética padrão utilizada foi a Pr14FebalCo16B6Nb0,1. Adições de elementos de liga como fósforo, cobre, alumínio, gálio e gadolíneo foram realizadas com o objetivo de melhorar as propriedades magnéticas do material padrão. A caracterização microestrutural dos ímãs foi realizada por microscopia óptica e MEV. A complexidade da microestrutura influencia o comportamento eletroquímico das ligas magnéticas. A literatura sobre este assunto é escassa. Assim, a resistência à corrosão das diferentes ligas preparadas ao longo do trabalho foi avaliada por espectroscopia de impedância eletroquímica e curvas de polarização potenciodinâmica. Foi estabelecida uma correlação entre as características microestruturais e o comportamento eletroquímico das ligas. Os resultados indicaram que adições de fósforo e alumínio em teores de até 1,0%p têm um efeito benéfico sobre as propriedades magnéticas e resistência à corrosão da liga padrão. A presença de cobre, por outro lado, diminui sensivelmente as propriedades magnéticas da liga padrão. / HDDR process has attracted great interest for producing polymer- bonded rareearth based magnets. It presents commercial advantages when compared with conventional sintered magnets owing to easy and low cost manufacturing. With the development of anisotropic powders using praseodymium, the expectations about this process grow e also the need for studying new compositions and alloy additions. In this work the magnetic properties of polymer-bonded magnets prepared with PrFeB magnetic alloys using HDDR process have been studied. Pr14FebalCo16B6Nb0,1 was used as the reference alloy Phosphorus, copper, aluminium, galium and gadolynium additions have been performed to increase the magnetic properties of the reference alloy. The microstructural characterization of the magnets has been carried out through optical microscopy and SEM. The complex microsctructure influences the electrochemical behavior of the magnetic alloys. The literature about this subject is scarce. Thus, the corrosion resistance of the different alloys prepared during this work was evaluated using electrochemical impedance spectroscopy and potentiodynamic polarization curves. A correlation between the microstructural features and the electrochemical behavior of the alloys has been established. The results showed that phosphorus and aluminium additions up to 1.0wt% had a beneficial effect on the magnetic properties and corrosion resistance of the alloys. Copper additions, on the other hand, strongly diminished the magnetic properties of the reference alloy.

La signalisation calcique est un mécanisme physiologique essentiel pour l’homéostasie cellulaire, et en particulier pour les cellules immunitaires telles que les lymphocytes B (LB). Chez l’homme, la caractérisation des molécules impliquées dans la signalisation calcique des LB est encore restreinte. Nous avons donc choisi d’étudier les molécules STIM1, STIM2, Orai1 et TRPC1 afin de rendre compte des modifications de la signalisation calcique observées dans deux modèles physiopathologiques : le Lupus Erythémateux Systémique (LES) et la Leucémie Lymphoïde Chronique (LLC). Pour les LB de LES, par rapport à des LB de témoins, ce travail a permis de montrer que la surexpression de la molécule STIM1 dans les LB de LES, surtout au stade des LB transitionnels, était associée avec un influx constitutif et extracellulaire de calcium et que cet influx était responsable d’une phosphorylation modérée de la MAPK Erk1/2 dans les cellules au repos. Cependant, cet effet positif est contrebalancé par un défaut de l’influx SOCE (strore operated calcium entry) et d’un défaut d’activation de la phosphorylation de la MAPK Erk après stimulation du récepteur à l’antigène des LB (BCR). Les effets positifs et négatifs observés sur la phosphorylation d.Erk1/2 sont directement attribuables au niveau d’expression de STIM1 comme nous l’avons démontré en sur-exprimant STIM1 dans des LB de témoins (vecteur pSTIM1-STIM1) ou en ayant recours à un siRNA spécifique de STIM1 dans les LB de LES. Le défaut d’activité régulatrice des LB de LES sur la prolifération des LT dans un modèle de co-culture autologue LT/LB en présence de CpG (activation du TLR9 des LB), et d’anticorps anti-CD3/CD28 (activation des LT) est levé en inhibant l’expression de STIM1 dans ces cellules ce qui permet de restaurer la production d.IL-10 par les LB de LES et la génération de LT régulateurs. Le défaut d’activation de la voie Erk/DNMT1/méthylation de l’ADN dans les LB de LES semble également contrôlée par le niveau d’expression de la molécule STIM1.Pour les LB CD5+ de LLC, l’analyse des partenaires calciques nous a permis de distinguer deux groupes de patients : un premier groupe qui exprime le complexe membranaire STIM1/TRPC1/Orai1 et un second groupe qui n’exprime qu’Orai1. La présence du complexe membranaire STIM1/TRPC1/Orai1 est associée avec un influx constitutif de calcium, la phosphorylation d’Erk1/2, et un défaut d’activation du signal SOCE après stimulation du BCR. Le rôle de la molécule CD5 sur l’influx constitutif des LLC du groupe I a été démontré en utilisant des siRNA spécifiques pourCD5 et en analysant la lignée B humaine Jok-1 transfectée avec CD5. Enfin, l’utilisation d’un anticorps anti-STIM1 est capable d’induire l’apoptose in vitro des LB de LLC du groupe I, alors que l’anticorps anti-CD20, rituximab, n’est efficace que sur les LLC du groupe II.En conclusion, cette étude ouvre de nouvelles perspectives diagnostiques et thérapeutiques en auto-immunité dans le LES et en cancérologie dans la LLC. / Calcium signaling is a central mechanism for cellular homeostasis, including for immune cells such as B lymphocytes (B cells). In human, the characterization of the molecules involved in B cell calcium signalisation is still limited and we have focused our study on STIM1, STIM2, Orai1 and TRPC1. In order to better understanding the role of these molecules, two pathologies, with known calcium dysregulations, were chosen : Systemic Lupus Erythematosus (SLE) and Chronic Lymphocytic Leukemia (CLL).For SLE B cells, compared to healthy control (HC) B cells, this work has established that overexpression of the STIM1 molecule characterizes SLE B cells, especially at the transitional B cell stage. STIM1 overexpression in SLE B cells was associated with a constitutive extracellular calcium influx that in turn contributes to the moderate phosphorylation of the MAPK Erk1/2. However, this positive effect is counterbalanced by a defective strore operated calcium entry (SOCE), and a defective Erk phosphorylation after B cell receptor (BCR) activation. The positive and negative effects on the MAPK Erk1/2 in SLE B cells are directly linked to level of STIM1 as demonstrated in HC B cells transfected with a STIM1 vector (pSTIM1-STIM1), or by using a specific siRNA to STIM1 (siSTIM1) in SLE B cells.The incapacity of SLE B cells to regulate T cell proliferation in an autologous co-culture T/B cell model is reversed by using siSTIM1 in SLE B cells. In this model, using siSTIM1 in SLE B cells also restores the production of IL-10 by B cells, and the generation of regulatory T cells. The defective Erk/DNMT1/DNA methylation pathway in SLE B cells is suspected to be under the control of STIM1 overexpression.For CD5+ CLL B cells, analysis of calcium partners has enabled us to distinguish two groups of patients: one group that expresses at the plasma membrane the complex STIM1/TRPC1/Orai1 and a second group that expresses onlyOrai1. The presence of the membrane complex STIM1/TRPC1/Orai1 in CLL group I is associated with a constitutive extracellular calcium influx, the basal phosphorylation of Erk1/2, and a defaut to mobilize SOCE upon BCR engagement. In the CLL group I patients, a role of CD5 on the constitutive extracellular calcium influx was shown using siRNA specific to CD5 and using the transfected CD5 expressing B cell line Jok-1. Finally, the in vitro use of an anti-STIM1 antibody is able to induce apoptosis in CLL B cells from group I patients, while the anti-CD20 antibody (rituxan) was only effective in the CLL B cells from group II patients.In conclusion, this study opens new diagnostic and therapeutic perspectives in autoimmunity and in cancer.

Thesis ( M Med (Virological Pathology))--University of Limpopo, 2010. / Introduction: Hepatitis B virus (HBV) is a serious problem worldwide causing various liver diseases such as chronic hepatitis and hepatocellular carcinoma (HCC). The pathogenesis of HBV related HCC is not well established. Hepatitis B X protein (HBx) plays an important role in the pathogenesis of HCC. HBx coded by HBV X gene enhances several cellular pathways in hepatocytes which may lead to HCC. The genetic variability of other HBV genomic regions plays a significant role in diagnosis, vaccine development and drug resistance. However, the genetic variability of HBV X gene is not well understood. In addition the dual basal core promoter mutations found within the X gene have been implicated in the inhibition of hepatitis B e antigen (HBeAg) expression. Studies focusing on HBV X gene are scarce in South Africa. Consequently HBV X gene variability may reveal interesting mutations and substitutions that are important in chronic liver diseases or HCC. This study aimed at characterising HBV X gene at a molecular level isolated from patients with different serological profiles. Methods: This was an exploratory study which used 20 stored sera (-70°C) collected from adult patients at Dr George Mukhari hospital, Pretoria. The samples were already tested for HBsAg, anti-HBs, anti-HBc and HBeAg serological markers (Elecsys, Roche Diagnostics, Penzburg, Germany). HBV DNA extraction was performed from serum using High Pure Viral Nucleic Acid Assay (Roche Diagnostics, Penzburg, Germany). Nested PCR assay was used for the amplification of 465 nucleotide HBV X gene. Sequencing of PCR positive samples was done using spectruMedix SCE2410 genetic analysis system. Six samples selected, were cloned into the pGEM®-T Easy vector system (Promega, Madison, USA). Three clones of each sample were selected and their plasmids purified using Pure Yield™ Plasmid Miniprep System (Promega, Madison, USA). The plasmid DNA was recovered using optimised nested PCR assay and sequenced. A total of 38 sequences were generated from the study and compared with reference strains retrieved from GenBank. Phylogenetic analysis based on HBV X gene sequences was done using MEGA 4 software to determine different genotype clusters. vi Results: HBV X gene was successfully detected and amplified in 20 study samples. The sequenced HBV X gene products revealed mutations and insertions. Particularly a six nucleotide insertion, GCATGG between nucleotides 1611 and 1618 which was detected in five samples. In addition, the six cloned samples confirmed the six nucleotide insertion and other mutations associated with inhibition of hepatitis B e antigen (HBeAg) detected in the study. The substitutions within HBx were detected in the N (1-50 amino acids) and C (51-154) terminals by comparing our sequences with archival sequences from GenBank. Important substitutions found within the N and C terminals were S31A, P38S, A42P, F73L, H94Y, P101S, K118T, D119N, I127T/N, K130M and V131I. These substitutions are associated with various biological functions and pathogenesis. Other substitutions with unknown functions detected in the study include A2G, A3G, A4G, C6W, P42S and V116L. Further mutations of T1753M, A1762T and G1764A associated with inhibition of HBeAg expression were detected in most samples and only one sample had C1766T mutation. Phylogenetic analysis resulted in A, C and D HBV genotypes. Five samples and 11 clones clustered with genotype D, two samples and four clones clustered with genotype C and finally 13 samples and 3 clones clustered with genotype A. Conclusion: HBV X gene was successfully characterised using various molecular methods. HBx substitutions detected are involved in various pathogenic effects and may present a risk of HCC for patients infected with HBV. Genotype D samples displayed most mutations/substitutions and this can be regarded as an important genotype with high risk of HCC. The detection of a six nucleotide insertion (GCATGG) in 5 samples may emerge as a new variant of genotype D. Furthermore triple mutations of T1753M/A1762T/G1764A within basal core promoter region were detected mostly in HBeAg negative samples. However further analysis of HBV X gene variability is needed.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

The Hepatitis B virus (HBV) chronically infects 350 million individuals worldwide, leading to mortality by end-stage liver disease, liver cirrhosis, and hepatocellular carcinoma. The vaccine to prevent HBV infection is highly effective but is not extensively available in endemic areas, resulting in high infection rates. Nucleoside analogue treatment of HBV has allowed for higher rates of viral clearance in infected individuals, but most patients must remain on therapy long term and viral resistance to the drugs is growing. The HBV viral genome is an episome in the nucleus of infected hepatocytes. It is called covalently closed circular (ccc) DNA and is highly stable, has a long half-life, and is the template for all viral transcription and progeny production. Nucleoside analogues do not directly target cccDNA, therefore many patients experience rebound when antiviral therapy is stopped. I have designed novel DNA binding proteins called zinc finger proteins (ZFPs) to specifically bind to the cccDNA in infected cells and inhibit viral transcription. Seven ZFPs targeting the model duck HBV (DHBV) and ten ZFPs targeting HBV were developed. Kinetic analyses of the purified ZFPs were performed, characterizing their specificity and binding properties. Using the DHBV tissue culture model system, I have demonstrated that the DHBV-specific ZFPs can specifically inhibit transcription from the viral template, resulting in reduced viral RNA, protein products and progeny virions. The DHBV-specific ZFPs were tested in primary duck hepatocytes (PDH) and in vivo in the Pekin duck model. ZFPs failed to express in PDH transduced by baculovirus vectors when DHBV was present in the cells. In vivo gene delivery of the ZFPs was carried out by portal vein injection of chitosan-based nanospheres. Unfortunately, non-specific reductions in viral levels masked any direct effect by the ZFPs. Testing of the HBV-specific ZFPs in tissue culture was hindered by a lack of transfectable cell culture model. A number of different transfection methods were tested to express the HBV-specific ZFPs, all without success. Further work is being carried out using baculovirus vectors to deliver the HBV-specific ZFPs to HBV-harbouring cell lines and HBV-infected scid-Alb/uPA chimeric mice with human liver cells. / Virology

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 112-116).

Recently, imagination and creativity is seen as keys for innovation and success factors .Imagination can create new idea and invent new things. It¡¦s a critical role to develop new markets for enterprises or dominate new industries. Meanwhile, the imagination is related to future. When imagination is use to predict the future, it is necessary to combine the knowledge base, creativity and the ideal value, and its focus is not on the accuracy of the prophecy, but rather the thoughts and actions triggered by this process. The new thinking is that the source of organizational innovation should come from the imagination of the leaders, business leaders must understand the vision and imagination influence than all other external information. Different from typical hotel industry, B&Bs give tourists more than just a place to stay, instead, they provide a place which full of local cultural and characteristics to enjoy. Since Taiwan government allowed resident of China visiting Taiwan from July 2008, B&Bs play a important role to attract these tourist. Therefore, more and more people started their business in B&Bs industry, but not everyone can be successful. So in this study, I focus on what relations are between the success in B&Bs and imagination? What is imagination process?

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobioloji Anabilim Dalı, 2009. / Kaynakça var.