This project represents a descriptive analysis of Forms I and II of the Luria-Nebraska Neuropsychological Battery and an investigation of the applicability of Item Response Theory in neuropsychological assessment. Test protocols of 1280 Form I examinees and 405 Form II examinees were analyzed by item and scale using Item Response Theory. The analysis consisted of investigation of the fit of LNNB data to the one and two-parameter IRT models, analysis of item and scale residuals and information values, comparison of traditional and IRT approaches in derivation of the Pathognomonic, Right Hemisphere and Left Hemisphere scales and comparison of two IRT approaches to the identification of biased items. In general, the one-parameter model did not fit the LNNB data. The two-parameter model, however provided a generally good fit to the data. Scale residuals and information functions indicate that the LNNB scales are unidimensional and accurately measure their underlying pyschological constructs. Item analysis identified several items on each scale that do not contribute to the measurement of the scalar trait. Suggestions were made for deletion, relocation or alteration of these items to improve their measurement properties. Substantial differences were found between Form I and Form II based on item characteristic curves and b-value differences. The nature of these differences suggested that the size and ability distribution of the Form II sample may have prevented accurate parameter estimation, obscuring the comparison of the two forms of the battery. A number of items on the Pathognomonic, right Hemisphere and Left Hemisphere scales were identified that contribute little to the measurement properties of these scales. Additional items not on these scales, were identified that are candidates for inclusion on these scales. Comparison of the statistical tests of b-value differences with ICC differences, for identification of potentially biased items, suggests that the latter method may be more efficacious in the neuropsychological domain. It is concluded that the LNNB is an accurate and content valid test of neuropsychological abilities; that IRT methods could improve the measurement properties of the scales and that ICC differences are an effective approach to item bias detection.

The study was planned to investigate issues relating to the Luria-Nebraska Neuropsychological Battery. The aims were to investigate the influence of age, sex and socio-economic status on performance on the Luria-Nebraska Neuropsychological Battery. A sample of forty males and forty females, stratified according to age (25-40 year olds and 50-60 year olds) and socio-economic status was selected. The results suggested that age formed a significant effect on the total and individual scale scores of the battery. There were no significant sex differences on the total score and most of the scale scores of the battery. Sex formed a significant variable on the performance on the intellectual processes and visual scales. A significant negative correlation was found between total and scale scores of the Luria-Nebraska Neuropsychological Battery and socio-economic status. The implications of these findings are discussed. / Thesis (M.A.)-University of Durban-Westville, Durban, 1991.

The factor structure of the Luria Nebraska Neuropsychological Battery (LNNB) Form II was examined. A principle components factor analysis was performed on a sample of 102 psychiatric and neurologic subjects. It was necessary to remove 45 items from the analysis due to perfect performance by most subjects. The results were orthogonally rotated to simple structure using a Varimax method of rotation, and then compared to previous LNNB Form I and Form II results. Thirty-three factors were generated in the Exploratory Factor Analysis (EFA) . There was a very high agreement with the factors from Form I. Only one new factor was identified that didn't have a comparable Form I factor, and this factor appears to have neurological support. The similarity of the factor solutions between the two forms supports the continued use of factors derived from Form I for the interpretation of Form II, and supports the underlying structure presupposed by Lurian constructs. The present study also tested the significance of the hypothesized factor structures through confirmatory factor analysis (CFA). No hypothesis about the underlying factor structure based on previous exploratory studies was supported. The CFA did suggest that the best factor solution to the LNNB Form II is one that (a) has correlated factors and (b) has items loading on more than one factor. The confirmatory results were interpreted as not supporting the current exploratory results, or the previous factor analytic results. Problems notwithstanding, researchers may be better directed to propose factor models for the LNNB that have correlated factors, and to work samples approaching the 10 to 1 recommended sample size for multivariate analysis. One conclusion that was drawn from the concurrence between the two Form II studies pertains to psychiatric populations used in both studies. It was necessary to exclude a large number of items in each study due to perfect performance by most of the subjects on those items. Most of the items removed were identical in both studies supporting the notion that a shortened version of the LNNB could be administered to psychiatric populations.

There is a growing appreciation for the insight mathematical models can yield on biological systems. In particular, due to the challenges inherent in experimental observation of disease progression, models describing the genesis, growth and evolution of cancer have been developed. Many of these models possess the common feature that one particular type of cellular population initiates a further, distinct population. This thesis explores two models containing this feature, which also employ branching processes to describe population growth. Firstly, we consider a deterministically growing wild type population which seeds stochastically developing mutant clones. This generalises the classic Luria- Delbruck model of bacterial evolution. We focus on how differing wild type growth manifests itself in the distribution of clone sizes. In our main result we prove that for a large class of wild type growth, the long-time limit of the clone size distribution has a general two-parameter form, whose tail decays as a power-law. In the second model, we consider a fully stochastic system of cells in a growing population that can undergo birth, death and transitions. New cellular types appear via transitions, examples of which are genetic mutations or migrations bringing cells into a new environment. We concentrate on the scenario where the original cell type has the largest net growth rate, which is relevant for modelling drug resistance, due to fitness costs of resistance, or cells migrating into contact with a toxin. Two questions are considered in our main results. First, how long do we wait until a cell with a specific target type, an arbitrary number of transitions from the original population, exists. Second, which particular sequence of transitions initiated the target population. In the limit of small final transition rates, simple, explicit formulas are given to answer these questions.

B rucella lipopolysaccharide is an important component of virulence in brucellosis. Recent research in macrophage models has shown that Brucella LPS does not behave like classical LPS by stimulating potent inflammatory responses. The central hypothesis of this work is that O-antigen is dynamic signaling molecular and participates in complex interactions with the host to promote productive infection. A corollary to this is that the host environment is dynamic, and Brucella has evolved mechanisms to cope with changing environments. In an effort to understand the contribution of Brucella LPS to virulence and pathogenesis, the function of a metabolic locus important in the synthesis of LPS has been demonstrated and complemented. The spontaneous loss of LPS expression has been characterized. Contribution of LPS to acquisition of the host environment in tissue culture and mouse models has been explored. This work demonstrated that genes outside the O-antigen biosynthesis ( manBA) cluster contribute to LPS biosynthesis. Further high frequency mutation involving manBA is partly responsible for observed dissociation of Brucella strains. Finally, work herein attempts to look at the role of LPS in acquisition of the host environment and shows that LPS is important for recruiting particular cell populations within a host model of brucellosis.

No abstract available. / Thesis (Ph.D.)-University of Natal, Durban, 1989.

Made available in DSpace on 2014-06-11T19:32:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-03-09Bitstream added on 2014-06-13T21:03:20Z : No. of bitstreams: 1 tuleski_sc_dr_arafcl.pdf: 2124446 bytes, checksum: 7b5e4db9e8340c73ccc549e2291cec30 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A presente pesquisa, de natureza conceitual, procurou compreender a obra de A. R. Luria (1902-1977) como determinada pela concretude de seu contexto histórico, isto é, a Rússia pós-revolucionária como marco inicial de seus estudos e pesquisas e, posteriormente, a União Soviética sob o regime stalinista. Para isso, foi realizada uma extensiva pesquisa das publicações deste autor, evidenciando a crescente sistematização dos conceitos e método para a compreensão da constituição da consciência humana, tomando-se por base seus fundamentos filosóficos e epistemológicos. Os estudos de Luria foram organizados por etapas - antes de Vigotski, em conjunto com ele e após sua morte - devido ao aparente redirecionamento dado às suas pesquisas, durante o stalinismo, que o fez concentrar-se mais na área da neuropsicologia. Observou-se que suas obras mais conhecidas no Ocidente quando desligadas de seus fundamentos marxistas, vêm dando base a apropriações indevidas de seus conceitos e associações a autores cuja base epistemológica é contrária. Entende-se que apenas o resgate da obra luriana em seu conjunto, bem como de seus fundamentos marxistas possibilita compreender o funcionamento cerebral como materialização das funções psicológicas superiores, de origem cultural, opondo-se ao reducionismo biológico ou subjetivo, hegemônico na atualidade. Para esta empreita, foi demonstrado que Luria deu continuidade aos pressupostos vigotskianos em suas pesquisas sobre o funcionamento cerebral e suas patologias, a despeito do acirramento do stalinismo na União Soviética após a morte de Vigotski, em 1934, superando a compreensão do homem como mais uma espécie sujeita, em seu desenvolvimento, às condições de maturação de seu organismo biológico, e, portanto, limitada por tais condições que independem de aspectos sócio-culturais, em direção a uma... / The present research, of conceptual nature, aimed at understanding the work of A. R. Luria (1902 - 1977) as determined by the concreteness of its historical context, i.e., the postrevolutionary Russia as the initial mark for his studies and research and, subsequently, the Soviet Union under Stalinist regime. In order to do so, extensive research was done into this author s publications, evidencing the increasing systematization of concepts and method for the understanding of how the human conscience is constituted, having its philosophical and epistemological foundations as basis. Luria s studies were organized in stages - before Vigotski, along with him and after his death - due to the apparent redirection given to his research, during Stalinism, which made him focus more on the neuropsychological area. It was observed that his most renowned pieces in the West when disconnected of its Marxist foundations have been giving basis to improper appropriations of its concepts and associations to authors whose epistemological basis is contrary. It is understood that only the rescue of Luria s work in its whole, as well as its Marxist foundations, enables the understanding of the brain work as materialization of the superior psychological functions, of cultural origin, opposing to the biological or subjective reductionism, presently hegemonic. For this purpose, it was demonstrated that Luria continued with the Vigotskian postulations in his research on the brain work and its pathologies, despite the incitement of Stalinism in the Soviet Union after Vigotski's death in 1934, overcoming the comprehension of the human being as one more species subject, in its development, to the conditions of maturation in its biological organism, and, therefore, limited by such conditions which prevent the social-cultural aspects, towards a new way of understanding human... (Complete abstract, click electronic access below)

The Luria-Nebraska Neuropsychological Battery (LNNB) was published in 1980 as an attempt to provide clinicians with a standardized version of the neuropsychological assessment and diagnostic procedures proposed by A. R. Luria and A, L. Christensen. Research on the LNNB included a series of factor analyses for each of eleven clinical scales. The analyses were completed on the combined scores obtained from a sample of normal, brain-damaged, and psychiatric populations. A second version of the LNNB was published in 1985 as a largely parallel version of Form I, but included changes in stimulus materials, administration procedures, and scoring procedures. The present study completed factor analyses on same eleven clinical scales using data generated with the newer LNNB Form II. The statistical procedures and criteria employed in the present investigation were identical to those used earlier on Form I to allow for comparisons between the two resulting sets of factor structures. The patient populations were different, however, in that all subjects in the current study were receiving inpatient care in a private psychiatric hospital which specializes in long-term treatment. Despite the changes in materials and procedures and the difference in subject parameters, the factors identified in the present investigation are similar to those seen in the Form I studies. However, two trends were observed when comparing the two sets of factor structures. First, in the present study several items were excluded from the statistical procedures because they were performed perfectly by almost everyone and the resulting scores lacked statistical variance. Second, more homogenous factors were obtained with the Form II analysis. That is, some of the complex LNNB Form I factors were reduced to two or more simpler factors. The results of the study lend support to Luna's conceptual model of higher cortical function and to the reliability of the LNNB as an assessment instrument.

Utilizada amplamente como agente terapêutico no tratamento da leucemia linfoblástica aguda (LLA), a L-Asparaginase II (ASNase) é uma enzima que atua diminuindo a concentração de asparagina livre no plasma. Dessa forma, impede o fornecimento de asparagina para a proliferação de células malignas, as quais ao contrário das células saudáveis, não conseguem sintetizar a asparagina. A ASNase utilizada atualmente no Brasil é importada, o que gera problemas com custo e abastecimento. Sendo assim, é notavelmente atrativa a procura por sistemas que apresentem níveis elevados de expressão de asparaginase e o encontro de formas de produzir tal enzima para um fácil acesso e, se possível, com menor potencial alérgico. Isso nos incentiva a estudar a produção biotecnológica de ASNase produzida em Escherichia coli BL21 (DE3) recombinante que super expressa esta enzima. O objetivo deste trabalho foi estabelecer, em agitador orbital e sistema descontínuo, os parâmetros do cultivo e indução da bactéria Escherichia coli BL21 visando à produção de ASNase, os quais serão úteis para futuros estudos em sistema descontínuo-alimentado. Nosso trabalho avaliou fatores que influenciam a fase de crescimento e/ou a fase de indução da E. coli BL21 (DE3): meio de cultivo baseado na composição elementar, controle do pH, uso de glicose ou glicerol como fonte de carbono, formação de acetato, tempo inicial e final da indução, permeabilização celular para secreção da ASNase, concentração de indutor, temperatura de pós-indução. Nós apresentamos uma estratégia para produção extracelular de ASNase em E. coli BL21 (DE3) pelo crescimento em meio Luria Bertani (LB) modificado para permeabilização celular. A produtividade volumétrica de ASNase extracelular foi 484 IU L h-1 em agitador orbital, correspondendo a 89 % de secreção após 24h de pós-indução com IPTG a 37 ºC. Isto representou rendimento 50 % maior para a ASNase total e 15,5 vezes mais secreção de ASNase em relação ao uso do meio LB modificado. Entretanto no cultivo em biorreator de 3 L nas mesmas condições (exceto a forma de aeração: 500 rpm de agitação e 1 vvm de vazão de ar, kLa = 88 h-1) operado em regime descontínuo foram obtidos resultados semelhantes aos cultivos em agitador orbital, sendo a produtividade volumétrica da ASNase extracelular igual a 525 IU L h-1 após 20 h de pós-indução. A biomassa obtida para agitador orbital e biorreator foi 3,26 e 2,63 g L-1, respetivamente. Por esse motivo, esses resultados foram considerados promissores para aumentar a produtividade nos futuros ensaios em biorreator operado em regime descontinuo-alimentado. / Widely used as a therapeutic agent in the treatment of acute lymphoblastic leukemia (ALL), L-Asparaginase II (ASNase) is an enzyme that works by reducing the concentration of free asparagine in plasma. Thus, it prevents the delivery of asparagine to the proliferation of malignant cells, which unlike healthy cell, cannot synthesize asparagine. ASNase currently used in Brazil is imported, which causes problems with cost and supply. Thus, the search for systems with high levels of asparaginase expression and the finding of ways to produce this enzyme for easy access and, if possible, with a lower allergic potential, are strikingly attractive. This encourages us to study the biotechnological production of ASNase in recombinant Escherichia coli BL21 (DE3) which super expresses this enzyme. The objective of this work was to establish, in shaker and batch bioreactor system, growth and induction parameters of the Escherichia coli BL21 aiming the production of ASNase, which will be useful for future studies in a fed-batch system. Our work evaluated factors that influenced the growth and induction phase of E. coli BL21 (DE3): culture medium based on elemental composition, pH control, use of glucose or glycerol as carbon source, formation of acetate, initial and final induction time, cellular permeabilization for ASNase secretion, inducer concentration, post-induction temperature. We performed a strategy for extracellular production of ASNase in E. coli BL21 (DE3) by growing in modified Luria Bertani (LB) medium for cell permeabilization. The volumetric productivity of extracellular ASNase was 484 IU L h-1 on shaker, which reached 89% secretion at 24 h of post-induction with IPTG at 37°C. This represented an increase yield of 50 % regarding to the total ASNase formed and 15.5 times the ASNase secretion as compared to that attained with LB modified. While in batch 2L-bioreactor cultivation under the same conditions (except for the aeration employed: 500 rpm of stirring and 1 vvm of air flow, kLa = 88 h-1) it was obtained similar results in relation to shaker cultures. The volumetric productivity of extracellular ASNase was 525 IU L h-1 at 20 h of post-induction. The biomass obtained for shaker and bioreactor were 3.26 and 2.63 g L-1, respectively. For this reason, we consider these promising results to increase productivity in future studies in bioreactor operated as fed-batch regimen.

Utilizada amplamente como agente terapêutico no tratamento da leucemia linfoblástica aguda (LLA), a L-Asparaginase II (ASNase) é uma enzima que atua diminuindo a concentração de asparagina livre no plasma. Dessa forma, impede o fornecimento de asparagina para a proliferação de células malignas, as quais ao contrário das células saudáveis, não conseguem sintetizar a asparagina. A ASNase utilizada atualmente no Brasil é importada, o que gera problemas com custo e abastecimento. Sendo assim, é notavelmente atrativa a procura por sistemas que apresentem níveis elevados de expressão de asparaginase e o encontro de formas de produzir tal enzima para um fácil acesso e, se possível, com menor potencial alérgico. Isso nos incentiva a estudar a produção biotecnológica de ASNase produzida em Escherichia coli BL21 (DE3) recombinante que super expressa esta enzima. O objetivo deste trabalho foi estabelecer, em agitador orbital e sistema descontínuo, os parâmetros do cultivo e indução da bactéria Escherichia coli BL21 visando à produção de ASNase, os quais serão úteis para futuros estudos em sistema descontínuo-alimentado. Nosso trabalho avaliou fatores que influenciam a fase de crescimento e/ou a fase de indução da E. coli BL21 (DE3): meio de cultivo baseado na composição elementar, controle do pH, uso de glicose ou glicerol como fonte de carbono, formação de acetato, tempo inicial e final da indução, permeabilização celular para secreção da ASNase, concentração de indutor, temperatura de pós-indução. Nós apresentamos uma estratégia para produção extracelular de ASNase em E. coli BL21 (DE3) pelo crescimento em meio Luria Bertani (LB) modificado para permeabilização celular. A produtividade volumétrica de ASNase extracelular foi 484 IU L h-1 em agitador orbital, correspondendo a 89 % de secreção após 24h de pós-indução com IPTG a 37 ºC. Isto representou rendimento 50 % maior para a ASNase total e 15,5 vezes mais secreção de ASNase em relação ao uso do meio LB modificado. Entretanto no cultivo em biorreator de 3 L nas mesmas condições (exceto a forma de aeração: 500 rpm de agitação e 1 vvm de vazão de ar, kLa = 88 h-1) operado em regime descontínuo foram obtidos resultados semelhantes aos cultivos em agitador orbital, sendo a produtividade volumétrica da ASNase extracelular igual a 525 IU L h-1 após 20 h de pós-indução. A biomassa obtida para agitador orbital e biorreator foi 3,26 e 2,63 g L-1, respetivamente. Por esse motivo, esses resultados foram considerados promissores para aumentar a produtividade nos futuros ensaios em biorreator operado em regime descontinuo-alimentado. / Widely used as a therapeutic agent in the treatment of acute lymphoblastic leukemia (ALL), L-Asparaginase II (ASNase) is an enzyme that works by reducing the concentration of free asparagine in plasma. Thus, it prevents the delivery of asparagine to the proliferation of malignant cells, which unlike healthy cell, cannot synthesize asparagine. ASNase currently used in Brazil is imported, which causes problems with cost and supply. Thus, the search for systems with high levels of asparaginase expression and the finding of ways to produce this enzyme for easy access and, if possible, with a lower allergic potential, are strikingly attractive. This encourages us to study the biotechnological production of ASNase in recombinant Escherichia coli BL21 (DE3) which super expresses this enzyme. The objective of this work was to establish, in shaker and batch bioreactor system, growth and induction parameters of the Escherichia coli BL21 aiming the production of ASNase, which will be useful for future studies in a fed-batch system. Our work evaluated factors that influenced the growth and induction phase of E. coli BL21 (DE3): culture medium based on elemental composition, pH control, use of glucose or glycerol as carbon source, formation of acetate, initial and final induction time, cellular permeabilization for ASNase secretion, inducer concentration, post-induction temperature. We performed a strategy for extracellular production of ASNase in E. coli BL21 (DE3) by growing in modified Luria Bertani (LB) medium for cell permeabilization. The volumetric productivity of extracellular ASNase was 484 IU L h-1 on shaker, which reached 89% secretion at 24 h of post-induction with IPTG at 37°C. This represented an increase yield of 50 % regarding to the total ASNase formed and 15.5 times the ASNase secretion as compared to that attained with LB modified. While in batch 2L-bioreactor cultivation under the same conditions (except for the aeration employed: 500 rpm of stirring and 1 vvm of air flow, kLa = 88 h-1) it was obtained similar results in relation to shaker cultures. The volumetric productivity of extracellular ASNase was 525 IU L h-1 at 20 h of post-induction. The biomass obtained for shaker and bioreactor were 3.26 and 2.63 g L-1, respectively. For this reason, we consider these promising results to increase productivity in future studies in bioreactor operated as fed-batch regimen.