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Receptor-mediated iron and haem transport in HaemophilusParsons, Tina January 1995 (has links)
No description available.
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The Relationship of Type A and Type B Coronary Behavior Patterns and Achievement StrivingAdams, Jolene Lowry 01 May 1985 (has links)
The purpose of this study was to conduct a systematic replication of the experiment of Burnam, Pennebaker, and Glass (1973) using an adult population and the Jenkins Activity Survey. Additionally, this study attempted to address the issue of whether the previous results would be substantiated when a non-college sample was used.
The subjects consisted of40 females and 40 males who volunteered to participate in the study. All subjects were given the Jenkins Activity Survey and randomly assigned to Condition I, the No Deadline condition, or Condition II, the Deadline condition. The subjects in the No Deadline condition were given arithmetic problems with no time limit instructions, and subjects in the Deadline condition were given arithmetic problems with instructions which stated a time limit.
The results indicated that college students performed differently than the employed adults used in this study. Unlike the original study, this study using adults did not find a significant main effect for the Deadline versus No Deadline condition. Although the interaction effects were statistically significant in both studies, the reported interaction effects were not similar.
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Amplitude and frequency modulations of oscillation modes in hot B subdwarf and white dwarf stars from Kepler photometry / Modulations d’amplitude et de fréquence des modes d’oscillation dans les étoiles sous-naines de type B et les naines blanches observées par le télescope spatial KEPLERZong, Weikai 17 October 2016 (has links)
Les interactions non linéaires entre modes de pulsation, induisant des modulations d'amplitude et de fréquence, sont difficiles à mettre en évidence avec les télescopes au sol en raison des temps caractéristiques en jeu, de l'ordre de la semaine, du mois, ou même de l'année. L'avènement des télescopes spatiaux comme KEPLER (opéré par la NASA) a considérablement changé la donne en apportant de nouvelles données pour ce domaine de recherche. Dans cette thèse, nous analysons les données photométriques obtenues avec KEPLER pour 24 étoiles compactes pulsantes, incluant 18 étoiles sous-naines de type B (sdB) et 6 naines blanches. Nous établissons que les modulations d'amplitude et de fréquence des modes d'oscillation sont un phénomène courant dans ces étoiles. Nous étudions en particulier deux étoiles : KIC 0862602, une naine blanche pulsante de type DB, et KIC 10139564, une étoile sdB variable à courtes périodes. KIC 0862602 et KIC 10139564 ont été observées sans interruption par KEPLER en cadence rapide pendant deux années pour la première et plus de trois ans pour la seconde. En analysant en détail ces données photométriques de très haute précision, nous mettons en évidence différents types de comportements affectant les composantes de triplets induits par la rotation stellaire. Les fréquences et amplitudes de ces modes montrent des variations soi périodiques soi irrégulières, ou demeurent constantes. Ces comportements peuvent être connectés à ceux prédits par les équations d'amplitude dans le cas de couplages non linéaires résonants entre modes, en particulier pour les temps caractéristiques des modulations. De plus, nous montrons que les modes en résonance constituant les triplets peuvent également interagir avec des modes extérieurs par le biais d'autres formes de résonances telle que la résonance à trois modes v 0 ~ v 1 + v 2 , une situation qui n'est pas prise en compte dans le cadre théorique existant. Ces études apportent pour la première fois une preuve claire de l'existence de mécanismes de couplages non linéaires entre modes d'oscillations dans les pulsateurs compacts. Cette découverte résonne comme un avertissement pour les projets visant à mesurer les taux de changement des périodes dus à l'évolution dans les étoiles compactes en général. Les modulations de fréquence d'origine non linéaire peuvent potentiellement empêcher toute mesure fiable de ces taux, à moins de corriger ces effets auparavant. Les modulations observées caractérisées dans cette thèse apportent un regard nouveau sur "l'astérosismologie non linéaire" et appellent à revisiter les méthodes d'analyse des courbes de lumière pour en extraire les modes d'amplitude et de fréquence variables. Dans un futur proche, nous anticipons davantage d'attention portée à ces phénomènes non inéaires dans différents types d'étoiles pulsantes observées depuis l'espace, ainsi qu'un regain d'intérêt pour la théorie non linéaire des oscillations stellaires en général. / Nonlinear mode interactions, inducing amplitude and frequency modulations, are difficult to observe from ground-based telescopes as these typical timescales of the modulations are of the order of weeks, months, or even years. The launch of space telescopes such as Kepler (operated by NASA) has tremendously changed the situation by providing new data for this research field. In this thesis, we analyze the Kepler photometric data observed for 24 compact pulsators, including 18 hot B subdwarf (sdB) stars and six white dwarf stars. We find that it is a common phenomenon that oscillation modes in these pulsating stars show amplitude and/or frequency variations. We focus in particular on two stars, KIC 08626021, a DB white dwarf, and KIC 10139564, a short period sdB star. KIC 08626021 and KIC 10139564 have been monitored by Kepler in short-cadence mode for nearly two years and more than three years without interruption, respectively. By analyzing in depth these high-quality photometric data, we find that the modes within triplets induced by rotation clearly reveal different types of behaviors : their frequency and amplitude may exhibit either periodic or irregular modulations, or remain constant. These various behaviors can be linked to those predicted within the amplitude equation formalism in the case of the nonlinear resonant mode coupling mechanism, particularly for the modulation timescales. Furthermore, we find that the triplet resonance modes can also interact with outside modes through other types of resonances such as the three-mode resonance v 0 ~ v 1 + v 2 , which is not considered within the current nonlinear theoretical frameworks. These findings constitute the first clear evidence of nonlinear resonant mode couplings occurring in compact pulsators. This should resonate as a warning to projects aiming at measuring the evolutionary change rate of pulsation periods in compact stars in general. Nonlinear modulations of the frequencies can potentially jeopardize any attempt to measure reliably such rates, unless they can be corrected beforehand. The observed modulations characterized in this thesis provide new insights to "nonlinear asteroseismology" and call for new methods to process the signals of variable modes from the observed light curves. We foresee that increasing attention will focus on these nonlinear phenomena in various types of pulsating stars observed from space in the near future, thus reviving interest in the nonlinear oscillation theory in general.
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Rôle du récepteur myéloïde à l’endothéline (ETB) au cours de l’hypertension artérielle / Role of myeloid endothelin-B receptors during experimental hypertensionGuyonnet, Léa 20 May 2016 (has links)
L’hypertension artérielle (HTA) est un problème de santé publique. Largement répandue dans le monde, elle touchait 40% des adultes âgés de plus de 25 ans et causait 9.4 millions de décès en 2008. Cette pathologie est la cause la plus commune de décès dans les pays développés et constitue un facteur de risque majeur d’atteintes cardiaques, rénales et cérébrales. Bien qu'étudiés depuis maintenant plus d'un demi-siècle, les mécanismes des atteintes systémiques liées à l'hypertension restent encore peu connus. L'augmentation de la pression artérielle est multifactorielle et découle aussi du dérèglement de certains systèmes tels le système rénine-angiotensine et le système endothéline. De récentes études ont suggéré un rôle de l’immunité innée dans le développement de l’HTA et des lésions qui y sont associées. L’endothéline-1 est un puissant vasoconstricteur. Sa production est déclenchée par différents stimuli dont l’AngII et des cytokines pro-inflammatoires. L’ET-1 agit via deux récepteurs : ETAR et ETBR. Pour ce projet, nous avons généré des souris ne possédant pas le récepteur ETB myéloïde (LysM-Cre Ednrb lox/lox). Ces souris ont été soumises à une perfusion chronique d’AngII associée à un régime hyper-sodé. Nous avons observé que les deux groupes de souris développent la même hypertension et les mêmes atteintes cardiaques. En revanche les atteintes des organes cibles sont moins importantes chez les souris LysM-Cre Ednrb lox/lox. La fonction rénale de ces dernières est préservée et, histologiquement, moins de lésions sont observées. Cette protection semble être due à l’incapacité des cellules myéloïdes à infiltrer les reins. En effet, la chimioattraction des cellules myéloïdes vers ET-1 est dépendante du récepteur ETB myéloïde. De plus, les cellules inflammatoires qui sont observées dans les reins des souris LysM-Cre Ednrb lox/lox présentent un phénotype anti-inflammatoire contrairement à leur contrôles. / Arterial hypertension is a major risk factor for atherosclerosis, coronary artery disease, stroke, and chronic kidney disease (CKD) and is one of the most prominent contributors to death worldwide. However, despite the frequency of hypertension, its cause in the majority of adults is unknown. Hypertension is complex, with no single mechanism entirely explaining the blood pressure (BP) rise in any given model. The past 50 years have seen growing evidence implicating the immune system. Recent data suggest that macrophages (M)/monocytes contribute to, and protect from, hypertension and its associated end organ injury. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor. Its production is triggered by multiple stimuli including Ang II and pro-inflammatory cytokines. ET-1 acts by binding to two distinct receptors, the endothelin-A (ETA) and the endothelin-B (ETB) receptors. Interestingly, ET antagonism can blunt BP elevation in an Ang II model suggesting that ET-1 largely mediates the effects of Ang II. Here, we have generated mice specifically lacking ETB receptors on myeloid cells. We have shown that the development of hypertension associated with Ang II infusion is not dependent on these cells. Similarly, the cardiac dysfunction seen after 6 weeks of Ang II was similar between knockout and control mice. Interestingly, mice deficient of ETB receptors on myeloid cells alone were protected from Ang II induced vascular dysfunction and kidney injury. This protection appeared to relate to an inability for ETB receptor deficient Mto infiltrate the kidneys due to impaired chemokinesis towards ET-1. Furthermore, the Minfiltrating he kidney in response to Ang II in myeloid ETB receptor deficient mice overwhelmingly possessed an anti-inflammatory phenotype.
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The effects of pantopon on the growth and motility of tetrahymena thermophilla type b-3 strain we 2035Okoko, Fabian J. 01 July 1982 (has links)
No description available.
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Streptococcus pneumoniae and haemophilus influenzae type B carriage in infants presenting to Zola Community Health Centre for routine immunizationMbelle, Nontombi Marylucy 23 May 2014 (has links)
Acute respiratory tract infections are the most common cause o f illness and death in the
pediatric population worldwide. It is estimated that 70 - 80% o f severe pneumonias in Africa
are caused by S.pnewnoniae (the pneumococcus) followed by H. influenzae type b.
Surveillance reveals that drug resistance is increasing worldwide, South Africa not being an
exception. This has considerably complicated the management o f infections caused by both
the pneumococcus and H. influenzae type b ( H ib ).
It is widely accepted that colonization of the nasopharynx even briefly precedes middle ear
infection and invasive pneumococcal disease. Early onset of colonization after birth has been
associated with early onset o f middle ear infections. Furthermore, colonized children are
able to transmit these organisms to other children.
Carriage o f pneumococci commonly occurs in young children. The carriage of resistant
pneumococci is usually limited to those serotypes carried in children. N ew conjugate
vaccines may be able to reduce colonization o f these serotypes.
This study was undertaken to determine the serotypes and susceptibility o f pneumococci and
H. influenzae type b, and the proportion o f healthy children colonized at Zola Community
Health Centre (ZCHC) in Soweto.
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Análise de tendência temporal: uma alternativa para avaliação do impacto da vacinação contra Haemophilus influenzae tipo b, no Brasil / Temporal Trend Analysis: an alternative for the evaluation of the impact of vaccination against Haemophilus influenzae type B in BrazilMiranzi, Sybelle de Souza Castro 23 November 2004 (has links)
As meningites representam um importante agravo no quadro sanitário nacional, por suas características epidemiológicas e por seu impacto sócio-econômico. O Haemophilus influenzae tipo b (HIB), causa infecções respiratórias e doenças invasivas como meningites, pneumonias, epiglotites, sinusites, bacteremias, otites e artrites. Entre essas enfermidades, a meningite tem sido a mais estudada, em virtude de sua alta morbi-mortalidade e por ser de notificação compulsória. A proposta deste trabalho foi a de avaliar a tendência, em série histórica, da morbimortalidade e da letalidade das meningites caudadas por HIB no Brasil, como uma alternativa para avaliação do impacto da vacinação específica. O estudo seguiu um delineamento observacional do tipo ecológico e relativo ao período de 1983 a 2002. Foram calculados os coeficientes de incidência, mortalidade e letalidade de meningites por HIB, a partir de base de dados do Ministério da Saúde e da Fundação Instituto Brasileiro de Geografia e Estatística. Para a análise de tendência destes indicadores foram estimadas retas de predição, com intervalos de confiança de 95%. Os softwares utilizados para a fase de gerenciamento e para a análise de dados foram: Excel, Epiinfo e Stata. No Brasil, entre 1983 e 2002, foram notificados 23.921 casos de meningites por HIB, dos quais 10.524 (43,99%) em menores de 1 ano e 9.269 (38,75%) na faixa de 1 a 4 anos. Os coeficientes de incidência, mortalidade e letalidade de maior magnitude foram observados nas faixas etárias de menores de 1 ano e de 1 a 4 anos. A partir de 1988, houve incremento na magnitude dos coeficientes de incidência e mortalidade. As regiões Norte e Nordeste apresentaram menor magnitude para esses indicadores, enquanto que para a letalidade, a região Nordeste apresentou indicadores de maior magnitude em menores de 1 ano. De modo geral, embora a letalidade tenha apresentado um padrão de declínio desde o inicio da série, sua magnitude permaneceu elevada até 2001. O impacto da vacinação sobre a letalidade, apenas a partir de 2002, sugere que esta pode levar até três anos, em média, para exercer efeito sobre o prognóstico das meningites por HIB. Com exceção da região Nordeste, a tendência para a incidência e a mortalidade no Brasil e regiões, foi semelhante, no período prévacinação (ascensão), detectando-se declínio após a introdução da vacina na rotina do Programa Nacional de Imunização. No Brasil e nas regiões Norte, Nordeste, Sul e Sudeste (nesta, em menores de 1 ano), a tendência da letalidade foi de declínio em toda a série. Nas regiões Centro-Oeste e Sudeste, o impacto da introdução da vacina sobre a incidência e a mortalidade foi mais precoce (1999-2000), em relação às outras regiões do estudo, talvez pelo fato dessas regiões terem apresentado cobertura vacinal mais elevada. O impacto da vacinação foi mais evidente sobre a incidência e a mortalidade do que sobre a letalidade. Os resultados revelaram um impacto positivo das estratégias de vacinação contra HIB, no Brasil e macrorregiões, inclusive em faixas etárias não vacinadas. Recomenda-se a monitorização contínua desses agravos, através de ações de Vigilância Epidemiológica, com aprimoramento do Sistema de Informação em Saúde. / Meningitis is an important disease within the national health system, due to its epidemiological characteristics and socioeconomic impact. The Haemophilus influenzae (HIB) type B causes respiratory infections as well as invasive diseases such as meningitis, pneumonias, epiglottitis, sinusitis, bacteremias, otitis and arthritis. Among these diseases, the meningitis has been the most studied due to its high morbi-mortality rate and also because requires compulsory notification. The purpose of this study was to evaluate the trend, considering the history series, regarding morbi-mortality and case fatality rates of meningitis caused by Hib in Brazil, as an alternative for the evaluation of the impact of a specific vaccination. This research was an ecologic observation from 1983 to 2002. The author calculated the incidence, mortality and case fatality rates of Hib meningitis, based on data from the National Health Department and the Geography and Statistics Brazilian Foundation Institute. In order to analyze these indicators\' trends, authors estimated prediction lines, with confidence intervals of 95%. The softwares used to manage and analyze data were: Excel, Epiinfo and Stata. In Brazil, from 1983 to 2002, 23.921 cases of Hib meningitis were notified. Among them, 10.524 (43.99%) in babies with less than one year and 9.269 (38.75%) in children with age varying from 1 to 4 years. The higher magnitude of incidence, mortality and case fatality rates were observed in the ages less than 1 year and varying from 1 to 4 years. Since 1988, the author observed an increment in the magnitude of the incidence and mortality rates. The North and Northeast regions presented a lower magnitude for these indicators, while for case fatality, the Northeast region presented indicators of higher magnitude in babies with age less than 1 year old. In general, although the case fatality rates presented a decreasing pattern since the beginning of the series, its magnitude was high until 2001. The impact of vaccination on case fatality rates was perceived only after 2002, suggesting that it can take three years, in average, to have some effect on the Hib meningitis prognosis. With exception to the Northeast region, the trends regarding the incidence and mortality in Brazil were similar, in the pre-vaccination period (increase), detecting a decrease after the introduction of vaccination in the routine of the do Programa Nacional de Imunização. In Brazil and in the North, Northeast, South and Southeast (age less than one year) regions, the case fatality trend was of decline during all series. In the Centerwest and Southwest regions, the impact of the vaccination introduction on the incidence and mortality rates was precocious (1999-2000), if compared to the other regions studied and maybe due to the fact that in these regions the vaccination achieved a greater amount of the population. The impact of vaccination was clearer on the incidence and mortality than on the case fatality rates. Results revealed a positive impact of the vaccination strategies against Hib in Brazil and in macro regions, including the age ranges that were not vaccinated. The author recommends the continuous monitoring of these diseases, through epidemiological surveillance actions and the improvement of the Health Information System.
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Desenvolvimento de processo para obtenção do método de conjugação do polissacarídeo capsular de Haemophilus influenzae tipo b com toxóide tetânico. / Development of process for the conjugation of capsular polysaccharide Haemophilus influenzae type b with tetanus toxoid.Lorthiois, Ana Paula de Almeida Aranha 18 February 2008 (has links)
Haemophilus influenzae type b (Hib) é uma importante bactéria Gram-negativa causadora de pneumonia, meningite e septicemia em crianças abaixo dos 5 anos de idade. A prevenção contra a doença pode ser alcançada pela imunização da população com vacina conjugada polissacarídeo-proteína, uma vez que a vacina de polissacarídeo não é eficiente. As vacinas conjugadas disponíveis comercialmente custam para o governo brasileiro cerca de US2,7 a dose, sendo necessárias no mínimo 3 doses para imunização completa. O presente estudo desenvolveu um novo método de conjugação de polissacarídeo capsular de Hib (PRP) com toxóide tetânico (TT). O método hidrazona baseia-se em 3 etapas simples: oxidação e derivatização de PRP com espaçador molecular e conjugação com TT na presença de uma carbodiimida e de um éster amino reativo. Após um estudo detalhado de cada etapa do método hidrazona, o novo processo mostrou excelentes resultados de rendimento mesmo após escalonamento. A imunogenicidade e o índice de avidez do conjugado hidrazona foram avaliados e os resultados encontrados foram comparáveis a vacina comercial Hiberix®. A técnica de HPSEC mostrou-se eficaz e o perfil cromatográfico do conjugado hidrazona foi muito similar ao da vacina Hiberix. Finalmente, o novo processo de conjugação de vacina permitiu o desenvolvimento de uma poderosa tecnologia constituindo uma excelente opção para o governo brasileiro. / Haemophilus influenzae type b (Hib) is an important encapsulated bacteria, which causes pneumonia, meningitis and septicaemia in infants. Prevention against infection is achieved by the currently available polysaccharide protein conjugate vaccine. However, due to its high production costs (around U$ 2,7 per dose) this formulation cannot be used in mass immunization programs in Brazil. In the present study, we developed a new method for the conjugation of Hib polysaccharide (PRP) and tetanus toxoid (TT). The hydrazone method is based on 3 singles steps: PRP oxidation, PRP derivatization with linker spacer and conjugation with TT in the presence of carbodiimide and an amino reactive ester. After detailed study of each step of method, the new process showed very good yield of conjugation even when it was scaled-up. The immunogenicity and the avidity index of hydrazone conjugate were evaluated and the results were comparable with those obtained with the commercial vaccine Hiberix®. The HPLC hydrazone profile was very similar to HPLC Hiberix profile. Finally, the new conjugation process allows the development of a powerful vaccine technology, constituting an excellent choice for the brazilian government.
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The Cyclotomic Birman-Murakami-Wenzl AlgebrasYu, Shona Huimin January 2007 (has links)
Doctor of Philosophy / This thesis presents a study of the cyclotomic BMW algebras, introduced by Haring-Oldenburg as a generalization of the BMW (Birman-Murakami-Wenzl) algebras related to the cyclotomic Hecke algebras of type G(k,1,n) (also known as Ariki-Koike algebras) and type B knot theory involving affine/cylindrical tangles. The motivation behind the definition of the BMW algebras may be traced back to an important problem in knot theory; namely, that of classifying knots (and links) up to isotopy. The algebraic definition of the BMW algebras uses generators and relations originally inspired by the Kauffman link invariant. They are intimately connected with the Artin braid group of type A, Iwahori-Hecke algebras of type A, and with many diagram algebras, such as the Brauer and Temperley-Lieb algebras. Geometrically, the BMW algebra is isomorphic to the Kauffman Tangle algebra. The representations and the cellularity of the BMW algebra have now been extensively studied in the literature. These algebras also feature in the theory of quantum groups, statistical mechanics, and topological quantum field theory. In view of these relationships between the BMW algebras and several objects of "type A", several authors have since naturally generalized the BMW algberas for other types of Artin groups. Motivated by knot theory associated with the Artin braid group of type B, Haring-Oldenburg introduced the cyclotomic BMW algebras B_n^k as a generalization of the BMW algebras such that the Ariki-Koike algebra h_{n,k} is a quotient of B_n^k, in the same way the Iwahori-Hecke algebra of type A is a quotient of the BMW algebra. In this thesis, we investigate the structure of these algebras and show they have a topological realization as a certain cylindrical analogue of the Kauffman Tangle algebra. In particular, they are shown to be R-free of rank k^n (2n-1)!! and bases that may be explicitly described both algebraically and diagrammatically in terms of cylindrical tangles are obtained. Unlike the BMW and Ariki-Koike algebras, one must impose extra so-called "admissibility conditions" on the parameters of the ground ring in order for these results to hold. This is due to potential torsion caused by the polynomial relation of order k imposed on one of the generators of B_n^k. It turns out that the representation theory of B_2^k is crucial in determining these conditions precisely. The representation theory of B_2^k is analysed in detail in a joint preprint with Wilcox in [45] (http://arxiv.org/abs/math/0611518). The admissibility conditions and a universal ground ring with admissible parameters are given explicitly in Chapter 3. The admissibility conditions are also closely related to the existence of a non-degenerate Markov trace function of B_n^k which is then used together with the cyclotomic Brauer algebras in the linear independency arguments contained in Chapter 4. Furthermore, in Chapter 5, we prove the cyclotomic BMW algebras are cellular, in the sense of Graham and Lehrer. The proof uses the cellularity of the Ariki-Koike algebras (Graham-Lehrer [16] and Dipper-James-Mathas [8]) and an appropriate "lifting" of a cellular basis of the Ariki-Koike algebras into B_n^k, which is compatible with a certain anti-involution of B_n^k. When k = 1, the results in this thesis specialize to those previously established for the BMW algebras by Morton-Wasserman [30], Enyang [9], and Xi [47]. REMARKS: During the writing of this thesis, Goodman and Hauschild-Mosley also attempt similar arguments to establish the freeness and diagram algebra results mentioned above. However, they withdrew their preprints ([14] and [15]), due to issues with their generic ground ring crucial to their linear independence arguments. A similar strategy to that proposed in [14], together with different trace maps and the study of rings with admissible parameters in Chapter 3, is used in establishing linear independency of our basis in Chapter 4. Since the submission of this thesis, new versions of these preprints have been released in which Goodman and Hauschild-Mosley use alternative topological and Jones basic construction theory type arguments to establish freeness of B_n^k and an isomorphism with the cyclotomic Kauffman Tangle algebra. However, they require their ground rings to be an integral domain with parameters satisfying the (slightly stronger) admissibility conditions introduced by Wilcox and the author in [45]. Also, under these conditions, Goodman has obtained cellularity results. Rui and Xu have also obtained freeness and cellularity results when k is odd, and later Rui and Si for general k, under the assumption that \delta is invertible and using another stronger condition called "u-admissibility". The methods and arguments employed are strongly influenced by those used by Ariki, Mathas and Rui [3] for the cyclotomic Nazarov-Wenzl algebras and involve the construction of seminormal representations; their preprints have recently been released on the arXiv. It should also be noted there are slight differences between the definitions of cyclotomic BMW algebras and ground rings used, as explained partly above. Furthermore, Goodman and Rui-Si-Xu use a weaker definition of cellularity, to bypass a problem discovered in their original proofs relating to the anti-involution axiom of the original Graham-Lehrer definition. This Ph.D. thesis, completed at the University of Sydney, was submitted September 2007 and passed December 2007.
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Autosomal Dominant Leukodystrophy with Autonomic Symptoms and Rippling Muscle Disease : Translational Studies of Two Neurogenetic DiseasesSundblom, Jimmy January 2011 (has links)
There is a large variety of diseases caused by single-gene mutations. Although most of these conditions are rare, together they impose a significant burden to the population. This thesis describes clinical and genetic studies of two single-gene diseases: 1) Adult-onset autosomal dominant leukodystrophy with autonomic symptoms (ADLD) caused by LMNB1 gene duplications, and characterized by autonomic, pyramidal and cerebellar symptoms. Spinal cords of patients with ADLD were studied by MRI and found to be thin, with high signal intensity in white matter. Histopathology showed loss of myelinated fibres with some reactive gliosis. DNA samples from four different families with ADLD were obtained, and the LMNB1 gene was screened for duplications. Single nucleotide polymorphism array revealed LMNB1 duplications in all ADLD families. LMNB1 mRNA and protein levels were assessed in white blood cells using quantitative polymerase chain reaction and Western blot, and increased levels of LMNB1 mRNA and lamin B1 protein could be demonstrated. We concluded that spinal cord atrophy in patients with ADLD is a valuable differential diagnostic sign, and that increased levels of LMNB1 can be detected in peripheral blood. 2) Rippling muscle disease (RMD) is caused by CAV3 gene mutations. Clinical features are percussion-induced muscle mounding, –rapid contractions and undulating muscle contractions (rippling). The CAV3 gene was sequenced in 38 members of a family with RMD. Twenty-two individuals had clinical features of RMD. No muscle weakness was seen. All patients with signs of RMD carried the p.A46T CAV3 mutation, showing that the p.A46T mutation was benign and that the diagnosis can be made clinically. In vitro contracture test results from 10 of the subjects were collected, but no association between pathological test results and RMD was found.
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