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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
151

LEUCEMIA LINFÓIDE AGUDA E AVALIAÇÃO DA EXPRESSÃO ANÔMALA MIELÓIDE NO PROGNÓSTICO DE CRIANÇAS E ADOLESCENTES DO MARANHÃO / ACUTE LYMPHOBLASTIC LEUKEMIA AND EVALUATION OF THE ANOMALOUS MYELOID EXPRESSION IN THE PROGNOSIS OF CHILDREN AND ADOLESCENTS OF THE MARANHÃO

Lopes, Thaiana da Costa 13 August 2012 (has links)
Made available in DSpace on 2016-08-19T18:16:04Z (GMT). No. of bitstreams: 1 dissertacao Thaiana.pdf: 2704967 bytes, checksum: e27a6cd767b0d6ac2256bec85730e19a (MD5) Previous issue date: 2012-08-13 / Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children and adolescents younger than fifteen years, with incidence peak between two and five years old. Several parameters have been evaluated for their importance in the prognostic evaluation of pediatric patients with ALL, of these, the evaluation of the anomalous myeloid expression prognosis of these pathologies. The aim of this work was to analyze the influence of myeloid anomalous expression in prognosis of children and adolescents with ALL of the state of Maranhão. It was evaluated 65 patients under 18 years diagnosed with ALL at the Instituto de Oncologia Maranhense Aldenora Belo (IMOAB) in São Luís, Maranhão. Laboratory data were obtained at diagnosis, made on the basis of morphological/ cytochemical and immunophenotype criteria. Other data were obtained from medical records. The sample was divided into groups with and without aberrant expression of myeloid antigens CD13 and CD33 for analysis with prognostic variables. The results indicated that the average age in the sample was 6,5 years, with the majority (69,2%) it was male children. The B-ALL was the most frequent type (83,1%). The mean percentage of blasts in our series was 75,8% in bone marrow and 46,6% in peripheral blood. Over ninety percent (90,8%) patients had L1 type morphology. The profile of blood test indicated the mean values of 32.373 leukocytes/mm3; 8,26 g / dl hemoglobin and 52.498 platelets/mm3. The anomalous myeloid expression occurred in 49,2% of the sample. The GBTLI-99 classification showed 56,9% of subjects with low risk of recurrence. At the end of the induction treatment period, 72,3% of children have responded positively in remission. The platelet count was significantly lower in without myeloid anomalous expression group (33.627 platelets/mm3, p = 0.01) compared to group that expressed this marker. About eighty-nine percent (88.9%) children with ALL-B and without myeloid aberrant expression had less than 50.000 platelets/mm3 (p = 0.01). Children with expression of CD33 were significantly older than those who did not express this marker (9,4 years, p = 0.01). It is concluded that the platelet count may be an important parameter to be analyzed in the prognosis of children with myeloid aberrant expression. The CD33 may be important in population with ALL and aberrant expression, since the CD13 was present in almost all cases. / A leucemia linfóide aguda (LLA) representa a neoplasia hematológica mais frequente em crianças e adolescentes menores de quinze anos, com pico de incidência entre dois e cinco anos de idade. Diversos parâmetros têm sido avaliados quanto à sua importância na avaliação prognóstica da população pediátrica com LLA, dentre estes, a avaliação da expressão anômala mielóide no prognóstico destas patologias. O objetivo deste trabalho foi analisar a influência da expressão anômala mielóide no prognóstico de crianças e adolescentes com LLA do estado do Maranhão. Foram avaliados 65 pacientes menores de 18 anos com diagnóstico de LLA assistidos no Instituto Maranhense de Oncologia Aldenora Belo (IMOAB), em São Luís, Maranhão. Os dados laboratoriais foram obtidos ao diagnóstico, realizado com base nos critérios morfológicos/citoquímicos e imunofenotípicos. Os demais dados foram obtidos a partir de prontuários. A amostra foi dividida em grupos com e sem expressão anômala mieloide dos antígenos CD13 e CD33 para análise com as variáveis prognósticas. Os resultados obtidos indicaram que a média de idade na amostra foi de 6,5 anos, sendo que a maioria (69,2%) se tratava de crianças do sexo masculino. A LLA-B foi o tipo mais frequente (83,1%). A porcentagem média de blastos em nossa casuística foi de 75,8% na medula óssea e de 46,6% em sangue periférico. Mais de noventa por cento (90,8%) dos pacientes apresentava morfologia do tipo L1. O perfil do hemograma indicou os valores médios de 32.373 leucócitos/mm3; 8,26 g/dl de hemoglobina e 52.498 plaquetas/mm3. A expressão anômala mielóide ocorreu em 49,2% da casuística. A classificação GBTLI-99 indicou 56,9% de sujeitos com baixo risco de recidiva. No final do período de indução do tratamento, 72,3% das crianças responderam positivamente com remissão da doença. A contagem de plaquetas foi estatisticamente inferior no grupo sem expressão anômala mielóide (33.627 plaquetas/mm3, p = 0,01) em relação ao grupo que expressou este marcador. Cerca de oitenta e nove por cento (88,9%) das crianças com LLA-B e sem expressão anômala mielóide apresentavam menos de 50.000 plaquetas/mm3 (p = 0,01). Crianças com expressão do CD33 foram significativamente mais velhas do que aquelas que não expressavam este marcador (9,4 anos, p = 0,01). Conclui-se que a contagem de plaquetas pode ser um importante parâmetro a ser analisado no prognóstico de crianças sem expressão anômala mielóide. O CD33 pode ser importante na caracterização da população com LLA e expressão anômala, já que o CD13 esteve presente em quase todos os casos.
152

Experiências anômalas na vida cotidiana: experiências extra-sensório-motoras e sua associação com crenças, atitudes e bem-estar subjetivo / Anomalous experiences in the daily life: extrasensorimotor experiences and their association with beliefs, attitudes and well-being

Machado, Fatima Regina 30 March 2009 (has links)
Este survey interseccional teve como objetivo verificar a prevalência de experiências anômalas extra-sensório-motoras (ou experiências psi) comparando características demográficas, práticas, crenças, religiosidade e níveis de bemestar subjetivo (BES) de experienciadores (EXPs) e não experienciadores (NEXPs) de psi. Para a coleta de dados, foi elaborado e aplicado o Questionário de Prevalência e Relevância de Psi (Q-PRP) com 35 itens, juntamente com a Escala de Bem-Estar Subjetivo (EBES) (Albuquerque e Tróccoli, 2004). Dos 306 respondentes (idades de 18 a 66 anos) que participaram da pesquisa, 82,7% alegaram ter vivenciado pelo menos uma experiência anômala extra-sensóriomotora. Não foi encontrada diferença significante entre EXPs e NEXPs em termos de gênero, renda, estado civil, religião e religiosidade. No entanto, verificou-se que EXPs crêem significantemente mais em percepção extra-sensorial, psicocinesia, reencarnação, vida após a morte e práticas alternativas. EXPs indicaram que suas experiências psi afetaram suas atitudes, crenças e tomadas de decisão. Tal influência está significativamente relacionada à atribuição de causalidade feita para as experiências psi vivenciadas. As atribuições de causalidade são coerentes com a crença, adesão ou postura religiosa dos EXPs. Quanto aos níveis de BES, os EXPs pontuaram mais no fator afetos negativos, o que sugere que EXPs têm um nível de BES mais baixo que os NEXPs. Os dados foram discutidos em detalhes enfatizando-se a complexidade de suas associações e correlações. Os resultados não são conclusivos, mas apontam tendências que deverão ser exploradas de forma mais aprofundada em próximos estudos. / The aim of this cross-sectional survey was to verify the prevalence of anomalous extrasensorimotor experiences (or psi experiences) and compare psi experiencers (EXPs) and non experiencers (NEXPs) in terms of demographic variables, beliefs, alternative practices and subjective wellbeing (SWB) levels. In order to collect data, it was used the 35-item Questionário de Prevalência e Relevância de Psi (QPRP) elaborated for this research, and the Escala de Bem-Estar Subjetivo (EBES) (Albuquerque e Trócoli, 2004). From the 306 respondents (age from 18 to 66), 82,7% claimed at least one psi experience. No significant differences between EXPs and NEXPs were found in terms of sex, income, marital status, religion and religiosity. However, EXPs believe significantly more in extrasensory perception, psychokinesis, reincarnation, survival after death, and alternative practices. EXPs indicated that psi experiences have affected their attitudes, beliefs and decisions. Such influence is significantly related to the attribution of causality they make to their own psi experiences. Attributions of causality were coherent to EXPs s beliefs. As to SWB, EXPs tend to punctuate higher in terms of negative affects than NEXPs, what suggests that EXPs have a lower level of SWB than NEXPs. Data were discussed in detail emphasizing the complexity of associations and correlations among them. Results are not conclusive, but point to tendencies which must be explored more profoundly in next studies.
153

Medidas de dispersão anômala de raios-x. / X-rays anomalous dispersion measurement.

Mazzaro, Irineu 13 January 1989 (has links)
Com a crescente disponibilidade de luz síncrotron tem-se utilizado cada vez mais a dispersão anômala (f´) no estudo de materiais. Apesar dos vários métodos já empregados na medida do fator de espalhamento atômico, ainda é pequeno o número de elementos abrangidos. Este trabalho apresenta uma contribuição à ampliação da gama de elementos mensuráveis através de um método interferométrico diferencial para a determinação experimental de f´. A sua demonstração é feita através de medidas em Selênio obtendo-se o mesmo nível de precisão do método &#933-&#933/2 usado em trabalhos anteriores. Esses dois métodos são criticados quanto ao limite de erro atingível devido à sua natureza não-absoluta. Uma técnica de preparação de amostras para materiais de baixo ponto de fusão é explorada, permitindo determinar f´absolutamente, com erro de 0,03 elétron. A medida do fator de espalhamento atômico através do desvio angular entre as reflexões de Bragg e Laue é proposta e testada com resultados de qualidade bastante inferior às técnicas interferométricas. A construção de interferômetros de raios X estáveis e de alto contraste é estudada quanto à seleção dos monocristais de silício e tratamento após o corte do dispositivo, atingindo-se contraste de 80% com estabilidade de uma milifranja por hora. / The use of anomalous dispersion (f\') in the study of materials has been increasing with the availability of synchrotron radiation. Although many methods have been designed for the measurement of the atomic scattering factor, the number of elements the cover is still small. This work presents a contribution to the widening of the range of measurable elements through a Differential interferometric method for the determination of f´. Its demonstration is achieved by measurements on Selenium, reaching the same level of accuracy obtained by the &#933-&#933/2 method used in previous work. These two methods are criticized in terms of the achievable errors due to its non-absolute nature. A technique for the preparation of samples with low melting point materials is developed, allowing the determination of f´ absolutely, with an error of 0,03 electron. The measurement of atomic scattering factor through the angular offset between Bragg and Laue reflections is proposed and tested, with low quality results compared to interferometric methods. The construction of high stability and good contrast X-ray interferometers is studied in terms of silicon single crystal selection and its treatment after device cutting. 80% contrast was achieved with a stability of one milifringe per hour.
154

Développement d'un système de mesure de temps de vol picoseconde dans l'expérience ATLAS / Development of a picosecond time-of-flight system in the ATLAS experiment

Grabas, Hervé 03 December 2013 (has links)
Cette thèse présente une étude de la sensibilité à la physique au delà du modèle standard et en particulier aux couplages anormaux entre les photons et les bosons W. Ceci est réalisé en détectant dans ATLAS les protons intacts après interaction et en mesurant leur temps de vol avec une précision de quelques pico-secondes de part et d’autre du détecteur central.Je décrirai également les photo-détecteurs de grande superficie avec une précision de quelques pico-secondes et les algorithmes de reconstruction de temps basés sur l’échantillonnage rapide du signal. Le circuit intégré spécifique SamPic pour une mesure de temps de très haute précision sera enfin présenté ainsi que les premiers résultats de mesure avec ce circuit. Ils montrent en particulier une précision exceptionnelle, meilleure que 5 ps, sur la mesure de temps entre deux impulsions. / In this thesis, we present a study of the sensitivity to Beyond Standard Model physics brought by the design and installation of picosecond time-of-flight detectors in the forward region of the ATLAS experiment at the LHC. The first part of the thesis present a study of the sensitivity to the quartic gauge anomalous coupling between the photon and the W boson, using exclusive WW pair production in ATLAS. The event selection is built considering the semi-leptonic decay of WW pair and the presence of the AFP detector in ATLAS. The second part gives a description of large area picosecond photo-detectors design and time reconstruction algorithms with a special care given to signal sampling and processing for precision timing.The third part presents the design of SamPic: a custom picosecond readout integrated circuit. At the end, its first results are reported, and in particular a world-class 5ps timing precision in measuring the delay between two fast pulses.
155

ZZ diboson measurements with the ATLAS detector at the LHC and study of the toroidal magnetic field sensors. / Mesure des dibosons ZZ avec le détecteure ATLAS auprès du LHC et Etude des sondes du champ magnetique toroidal

Protopapadaki, Eftychia Sofia 23 September 2014 (has links)
Les particules élémentaires ainsi que leur interactions sont décrites par le Modèle Standard. Malgré son grand succès, il y a encore des questions à répondre. Dans cette thése, le processus du Modèle Standard ZZ, lorsque les deux bosons Z se désintègrent en paires de leptons, a été étudié. Les données utilisées ont été prises par le détecteur ATLAS durant l'année 2012, ce qui correspond à une luminosité intégrée de 20 fb-1. L'énergie dans le centre de masse était de 8 TeV. Tous les éléments de l'analyse sont présentés dans ce document: la sélection du signal et son efficacité, l'estimation du bruit de fond, les systématiques associées à la mesure, ainsi que la méthode statistique employée pour l'extraction de la section efficace. La section efficace du processus ZZ sur couche de masse a été mesurée à 6.98±0.41(stat.)±0.36(syst.)±0.20(lumi) pb. La section efficace pour chaque canal a été aussi mesurée dans une volume cinématique ``restreint'', proche du volume reconstruit. Toutes les mesures obtenues sont en accord avec les prédictions theoriques. L'auto-interaction des bosons neutres est interdite dans le Modèle Standard. Si des couplages à trois bosons sont observés, ceux-ci indiqueront donc la présence d'une nouvelle physique. Des observables sensibles à la présence des couplages anormaux ont été examinées. L'impulsion transverse du boson le plus énergétique s'est avérée une des plus sensibles, et elle a été donc utilisée pour l'extraction des limites à 95% CL sur les couplages anormaux. Toutes les limites obtenues sont compatibles avec le Modèle Standard. La connaissance du champ magnétique toroïdal dans le détecteur ATLAS est essentielle pour l'estimation précise de la masse des particules. Une étude sur les senseurs utilisés pour la construction de la carte de champ du détecteur ATLAS a montré que 97% des senseurs sont fiables. La carte de champ existante a été examinée, et malgré l'observation d'anomalies, celles-ci ne sont pas susceptibles d'affecter la détermination de l'impulsion des muons, ni donc de l'estimation de la masse du boson de Higgs. / Elementary particles and their interactions are described by the Standard Model. Even successful, there are still some unanswered questions which need to be addressed. In this work, the ZZ Standard Model process was studied in the leptonic decay channel. The data used were collected by the ATLAS detector during 2012 and correspond to an integrated luminosity of 20 fb-1. The center of mass energy was 8 TeV. All the analysis elements, such as the signal selection and efficiencies, the background estimation, the measurement uncertainties and the statistical method employed for the cross section extraction, are discussed in this document. The total ZZ on-shell cross section is measured to be 6.98±0.41(stat.)±0.36(syst.)±0.20(lumi) pb. A measurement of the on-shell ``fiducial'' cross section, defined in a volume close to the reconstructed one, was also performed for each decay channel. Both total and fiducial measurements are in agreement, within uncertainties, with the SM predictions. The neutral boson-self interactions are forbidden in the SM. Therefore, if triple gauge boson couplings are observed, they will indirectly point to the existence of new physics. Observables sensitive to the presence of anomalous triple gauge couplings, along with the optimal binning were investigated. The traverse momentum of the most energetic boson was among the most sensitive observables, and it was thus used in order to extract 95% CL limits on the anomalous coupling parameters. All observed limits are found to be compatible with the SM expectations. In the framework of this thesis a performance study was conducted. In order to increase particles mass measurement precision, the accurate knowledge of the toroidal magnetic field inside the detector is essential. The sensors used for the production of the ATLAS toroidal magnetic field map were studied, and it was found that more than 97% of these sensors are reliable. The existing magnetic field map was probed, and even though inaccuracies were observed, they are not expected to impact muon momentum estimation and thus not to bias the Higgs boson mass measurement.
156

Investigation and Evaluation of a Bi-Polar Membrane Based Seawater Concentration Cell and Its Suitability as a Low Power Energy Source for Energy Harvesting/MEMS Devices

Merz, Clifford Ronald 27 October 2008 (has links)
It has long been known from Thermodynamics and written in technical literature that, in principal, instant energy can be made available when dilute and concentrated solutions are mixed. For example, a river flowing into the sea carries with it a physical-chemical potential energy in its low salt content, some of which should be recoverable. As also known, a naturally occurring, diffusion-driven, spontaneous transport of ions occurs throughout a solution matrix, thru barrier interfaces, or thru ion-selective membranes from the side containing the salts of higher concentration to the compartments containing the more dilute solution to effect the equalization of concentration of the ionic species. Since this ion movement consists, preferentially, of either cations or anions, it leads to a charge separation and potential difference across the membrane, otherwise known as a membrane potential. Eventually, when the concentrations in the compartment are the same, the cell ceases to function. However, if operated as a fuel cell with its respective concentrations continually replenished, equilibrium at a specific value of potential difference is established. To capture the energy of this potentially significant albeit low power energy source, a suitable energy extraction device is required. The focus of this Ph.D. research effort is to address the concept, research and evaluation of a Bi-Polar membrane based seawater concentration cell and its suitability as a low power energy source for Energy Harvesting/MEMS devices (patent pending).
157

Precision measurement of the e+e− → π + π−(γ ) cross-section with ISR method

Wang, L.-L. 26 May 2009 (has links) (PDF)
Vacuum polarization integral involves the vector spectral functions which can be experimentally determined. As the dominant uncertainty source to the integral, the precision measurement of the %born cross section of $e^+e^-\rightarrow\pi^+\pi^-(\gamma)$ as a function of energy from $2\pi$ threshold to 3GeV is performed by taking the ratio of $e^+e^-\rightarrow\pi^+\pi^-(\gamma)$ cross section to $e^+e^-\rightarrow\mu^+\mu^-(\gamma)$ cross section which are both measured with {\babar\ }data using ISR method in one analysis. Besides that taking the ratio of the cross sections of the two processes can cancel several systematic uncertainties, the acceptance differences between data and MC are measured using the same data, and the corresponding corrections are applied on the efficiencies predicted by MC which can control the uncertainties. The achieved final uncertainty of the born cross section of $e^+e^-\rightarrow\pi^+\pi^-(\gamma)$ in $\rho$ mass region ($0.6\sim0.9$GeV) is 0.54\%. As a consequence of the new vacuum polarization calculation using the new precision result of the $e^+e^-\rightarrow\pi^+\pi^-(\gamma)$ cross section, the impact on the SM prediction of muon anomalous magnetic moment $g-2$ is presented, which is also compared with other data based predictions and direct measurement.
158

The hematopoietic transcription factor RUNX1 : a structural view

Bäckström, Stefan January 2004 (has links)
<p>The malfunction of the transcriptional regulator RUNX1 is the major cause of several variants of acute human leukemias and its normal function is to regulate the development of the blood system in concert with other transcriptional co-regulators. RUNX1 belongs to a conserved family of heterodimeric transcription factors that share a conserved DNA binding domain, the Runt domain (RD), named after the first member of this group – Runt - found in Drosophila melanogaster. The binding partner CBFβ serves as a regulator of RUNX by enhancing its DNA binding affinity through an allosteric mechanism.</p><p>The main focus ofo my thesis work has been the crystallization and structural analysis of the RUNX1 RD and involved also more technical methodological aspects that can be applied to X-ray crystallography in general.</p><p>The high resolution crystal structure of the free RD shows that this immunoglobulin-like molecule undergoes significant structural changes upon binding to both CBFβ and DNA. This involves a large flip of the L11 loop from a closed conformation in the free protein to an open conformation when CBFβ and/or DNA are bound. We refer to this transition as the “S-switch”. Smaller but significant conformational changes in other parts of the RD accompany the “S-switch”. We suggest that CBFβ triggers and stabilizes the “S-switch” which leads to the conversion of the RD into a conformation enhanced for DNA binding.</p><p>During the structural analysis of the RD we identified two chloride ions that are coordinated by residues otherwise involved in DNA binding. In electrophoretic mobility-shift analyses (EMSA) we demonstrated a chloride ion concentration dependent stimulation of the DNA binding affinity of RUNX1. We further showed by NMR line width broadening experiments that the chloride binding occurred within the physiological range. A comparable DNA binding stimulation of RUNX1 was seen in the presence of negative amino acids. This suggests a regulation of the DNA binding activity of RUNX1 proteins through acidic amino acid residues possibly provided by activation domains of transcriptional co-regulators that interact with RUNX1.</p><p>The use of the anomalous signal from halide ions has become a powerful technique for obtaining phase information. By replacing the sodium chloride with potassium bromide in the crystallisation conditions of the RD, we could demonstrate in a single wavelength anomalous diffraction (SAD) experiment that the anomalous signal from 2 bromide ions were sufficient to phase a 16 kDa protein. Due to lack of completeness in the low-resolution shells caused by overloaded intensities, density modification schemes failed and the resulting electron density maps were not interpretable. By combining the highresolution</p><p>synchrotron data with low-resolution data from a native data set collected on a home X-ray source, the density modified bromide phases gave easily traceable maps.</p>
159

Superveniens och dess plats inom anomal monism : En analys av debatten mellan Donald Davidson och Jaegwon Kim / Supervenience and its place within Anomalous Monism : An analysis of the debate between Donald Davidson and Jaegwon Kim

Beckman, Emma January 2006 (has links)
<p>Denna uppsats analyserar den medvetandefilosofiska debatten mellan Donald Davidson och Jaegwon Kim rörande Davidsons tes om det mentalas superveniens på det fysiska. Tesen utgör ett element i Davidsons generella teori om relationen mellan det mentala och det fysiska; anomal monism. Författaren frågar sig om Kim har rätt i att tesen om mental superveniens inte är tillräcklig för att garantera det mentala kausal kraft. I uppsatsen analyseras de båda filosofernas ståndpunkter i debatten med speciell tonvikt på deras respektive definitioner av superveniensbegreppet. Med utgångspunkt i detta argumenterar författarinnan att Kim i viss utsträckning kan sägas ha missförstått Davidsons superveniens-begrepp. Kim har definierat "svag" respektive "stark" och velat tolka Davidsons superveniens som tillhörande den sistnämnda sorten. Uppsatsförfattaren intar en ståndpunkt motsatt Kims och menar att Davidsons superveniensbegrepp snarare bör förstås som en variant av svag superveniens, men konstaterar samtidigt att det inte är helt säkert att dennes superveniens alls kan inordnas i någon av dessa kategorier; dessa refererar till "möjliga världar", vilka Davidson vägrar acceptera.</p> / <p>This paper analyses the debate between Donald Davidson and Jaegwon Kim concerning Davidsons idea of the supervenience of the mental upon the physical. This thought is part of Davidson's general theory of the relation between mind and body; anomalous monism. The author asks wherther Kim is right that mental supervenience is insufficient to gurantee the mental causal power. The paper analyses the standpoints of both philosophers, especially regarding their definitions of "supervenience" and argues that Kim, to some extent, can be said to have misunderstood Davidson's notion of supervenience. Kim has offered definitons of "weak" and "strong" supervenience and interpreted Davidsons supervenience as being of the kind last mentioned. The author takes a standpoint opposite of Kim's and argues that Davidson's notion of supervenience is better understood as weak supervenience, but at the same time notes that it is by no means obvious that Davidsons supervenience can be said to belong to either of these categories since these refer to "possible worlds", which Davidson refuses to accept.</p>
160

The hematopoietic transcription factor RUNX1 : a structural view

Bäckström, Stefan January 2004 (has links)
The malfunction of the transcriptional regulator RUNX1 is the major cause of several variants of acute human leukemias and its normal function is to regulate the development of the blood system in concert with other transcriptional co-regulators. RUNX1 belongs to a conserved family of heterodimeric transcription factors that share a conserved DNA binding domain, the Runt domain (RD), named after the first member of this group – Runt - found in Drosophila melanogaster. The binding partner CBFβ serves as a regulator of RUNX by enhancing its DNA binding affinity through an allosteric mechanism. The main focus ofo my thesis work has been the crystallization and structural analysis of the RUNX1 RD and involved also more technical methodological aspects that can be applied to X-ray crystallography in general. The high resolution crystal structure of the free RD shows that this immunoglobulin-like molecule undergoes significant structural changes upon binding to both CBFβ and DNA. This involves a large flip of the L11 loop from a closed conformation in the free protein to an open conformation when CBFβ and/or DNA are bound. We refer to this transition as the “S-switch”. Smaller but significant conformational changes in other parts of the RD accompany the “S-switch”. We suggest that CBFβ triggers and stabilizes the “S-switch” which leads to the conversion of the RD into a conformation enhanced for DNA binding. During the structural analysis of the RD we identified two chloride ions that are coordinated by residues otherwise involved in DNA binding. In electrophoretic mobility-shift analyses (EMSA) we demonstrated a chloride ion concentration dependent stimulation of the DNA binding affinity of RUNX1. We further showed by NMR line width broadening experiments that the chloride binding occurred within the physiological range. A comparable DNA binding stimulation of RUNX1 was seen in the presence of negative amino acids. This suggests a regulation of the DNA binding activity of RUNX1 proteins through acidic amino acid residues possibly provided by activation domains of transcriptional co-regulators that interact with RUNX1. The use of the anomalous signal from halide ions has become a powerful technique for obtaining phase information. By replacing the sodium chloride with potassium bromide in the crystallisation conditions of the RD, we could demonstrate in a single wavelength anomalous diffraction (SAD) experiment that the anomalous signal from 2 bromide ions were sufficient to phase a 16 kDa protein. Due to lack of completeness in the low-resolution shells caused by overloaded intensities, density modification schemes failed and the resulting electron density maps were not interpretable. By combining the highresolution synchrotron data with low-resolution data from a native data set collected on a home X-ray source, the density modified bromide phases gave easily traceable maps.

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