932 resultados para stepwise selection to cefotaxime resistance


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O presente trabalho se ocupará com uma perícope do cap. 26, dos v. 12-19 do livro de Deuteronômio. Através do método sociológico propomos compreendê-la, primeiro como uma comunidade de pobres que está no campo, diante da catástrofe do pré-exílio em 722 a.C., portanto no reino do norte. Segundo que estes pobres formaram uma comunidade viva, vibrante, de superação e de resistência, contra a força interna que era a monarquia e contra uma força externa a invasão assíria, e não somente um agrupamento de sujeitos (levita, estrangeiro, órfão e viúva) que somente se lamentava diante das dificuldades. Com a utilização deste instrumental sociológico, nos possibilitou descobrir que esta comunidade de pobres tinha esperança, e aliás pensou uma esperança inovadora.

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Os ideais de liberdade exigiram do povo negro diferenciadas práticas para romper com o sistema escravista. Eram as rebeliões em navios, os atos de infanticídio, os justiçamentos dos feitores, as revoltas, além de participações em movimentos libertários e formações de quilombos. Dentre estas formas de organização, o quilombo foi fenômeno essencial nos mais de 300 anos de escravismo no Brasil. Em cada região existiam quilombos, pois para a população negra, cativa ou não, esse era o melhor meio de alcançar a liberdade, um meio coletivo para enfrentar o sistema. O Quilombo do Urubu representou a insistência em garantir a condição humana que o regime escravista negava, sobretudo às mulheres, aos homens e às crianças negras. Essa era uma força que saía de suas entranhas como grito de liberdade, configurada nas fugas em busca de um lugar que lhes assegurasse aproximação de uma vida digna e que pudessem orgulhar-sedo seu porte físico e da sua cultura. Todo esse desprendimento, além de uma força física, exigia um completo conhecimento histórico e espiritual, resguardado pela religiosidade que fortalecia seus espíritos para lutar contra toda negação de humanidade do século XIX no subúrbio da capital baiana. A líder Zeferina, inconformada com a exclusão social de seu povo negro, e entusiasmada pelo poder de herança de ancestralidade, pelo conhecimento de raiz da cultura matrilinear angolana, pelo profundo conhecimento histórico de resistência da rainha Nzinga Mbandi e pela tradição de quilombolas e guerreiras, viveu e lutou pelo sonho de liberdade. Hoje, a chama desse poder é mantida acesa na caminhada de celebração do 20 de novembro pela comunidade de Pirajá e arredores, enquanto referencial de resistência negra na luta contra as exclusões sociais vigentes.(AU)

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O trabalho desenvolvido com adolescentes, pensando na promoção de sua saúde, bem como em seu desenvolvimento saudável por meio de espaços que atendam suas necessidades, tem sido de responsabilidade também de organizações sociais. Em especial, quando se tem o objetivo de prepará- los para o mundo do trabalho, porém com uma proposta mais ampla, ou seja, como uma preparação para suas relações na vida, pela passagem de um processo de aprendizagem, de amadurecimento, por meio da construção de ações significativas para vida. Esta é a proposta do Centro de Orientação ao Adolescente de Campinas COMEC , organização não governamental, que conta com um Progr ama de Aprendizagem Profissional- PAP . Sendo assim, esse estudo tem como objetivo caracterizar, por meio de prontuários, uma amostra de 280 adolescentes, compreender a percepção deles no processo vivido e identificar as expectativas na admissão, demissão e desligamento do programa - PAP. A pesquisa teve como participantes adolescentes de 14 a 17 anos, do gênero feminino e masculino, do ensino fundamental e médio (7ª série E.F até 3ª série E.M). Os formulários foram preenchidos em três momentos: primeiro quando o adolescente participava da seleção para ingressar no programa, segundo, quando ele iniciava o trabalho na empresa e no término do contrato do adolescente com o programa. Os resultados obtidos por meio dos prontuários dos adolescentes mostraram que a percepção que eles têm a respeito do programa é positiva. Perceberam-se sentimentos de medo, insegurança, alegrias e desejos a respeito das atividades que os preparam para a inserção no mercado formal de trabalho, e o quanto o acompanhamento pelo programa permite outro olhar para esta inclusão. Ainda que o trabalho juvenil não seja a solução para as necessidades econômicas de muitas famílias, o trabalho educativo tem sido visto como uma forma de permitir que o adolescente vivencie sua primeira experiência de trabalho, respeitando sua condição de pessoa em desenvolvimento. Porém, em alguns casos, acabam por contribuir de forma significativa no orçamento familiar.(AU)

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Background The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors. Results Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism. Conclusion We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.

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The role of nutritional supplementation is of increasing interest with regard to ocular disease. Randomised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration, and formulations are now being developed for use by people with diabetes and diabetic retinopathy. The aim of this review was to synthesise the evidence for use of nutritional supplementation in type 2 diabetes. MEDLINE and EMBASE databases were searched using a systematic approach. Only double-masked randomised controlled trials were selected. A total of 50 trials were identified as suitable for inclusion. The potential role of alpha-lipoic acid, chromium, folic acid, isoflavones, magnesium, Pycnogenol®, selenium, vitamin C, vitamin E, and zinc in the treatment of type 2 diabetes is discussed. The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors. Chromium was the most studied supplement, accounting for 16 of the 50 trials. A majority of the trials found a positive effect of chromium on fasting plasma glucose. Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures, but only when combined with soy proteins. Vitamin E is reported to reduce oxidative stress at levels of 200 mg day-1 or more.

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The nutritional requirements for the vegetative growth of B. stearothermophilus strains NCIB 8919, NCTC lO,OO3 (wild) were found to be DL-methionine, biotin, nicotinic acid, thiamin, glucose and mineral salts. Strains NCIB 8920 required in addition L-tryptophan. B. stearothermophilus NCTC lO,OO3 (mutant) grew in a medium containing only glucose and mineral salts. Separate chemically defined media for the growth of Bacillus stearothermophilus strains NCIB 8919, 8920, NCTC lO,OO3 (wild) and NCTC lO,OO3 (mutant) were developed. Optimally aerated culture of B. stearothermonhilus NCTC lO,OO3(mutant) required 1.0 x 10-4 M. Mn2+ and 2.4 x 10-3 M. glutamic acid for optimal sporulation. Specific nutrient depletion of growth affected percentage sporulation. Spore suspensions of B. stearothermophilus NCTC 10,003 (mutant) were prepared from media in which sulphate (SO4-), nitrogen (N-),phosphate (Po4-), carbon (C-), magnesium-carbon simultaneously (Ng-C-) depleted growth. The heat resistance, dormancy and chemistry of these spores varied considerably. B. stearothermophilus NCTC 10,003 10,00310,00(mutant) spores prepared from carbon depleted cultures containing high and low concentrations of calcium, iron or manganese showed variations in heat resistance,dormancy and chemical composition. Progressive increase in the concentration of medium calciumfrom 1.0 X 10-5  M to 1.4 X 10-4 M. progressively increased theheat resistance of B. stearothermophilus NCTC 10,003 (mutant) spores prepared from nitrogen depleted cultures (N-). The thermodynamic functions for germination rate, magnesium and manganese release of N- and SO4- spores were within the range expected of enzymic reactions. The thermodynamic functions for the breaking of dormancy in SO4- spores and that for the release of D.P.A. were identical. Sublethal heating of SO4- spores (96.5°C and below) induced dormancy in these spores, whereas heating above 96.5°C gave rise to heat activation. Pooled results of the chemical analyses of all spore types studied showed that the concentration of D.P.A. and calcium were positively related to heat resistance whereas magnesium concentration and Mg/Ca molar ratio were inversely proportional to heat resistance.

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This thesis examines the involvement of the French Freemason movement in the Resistance during the Occupation of France by the Germans 1939-1945, its relationship with the Vichy government and the effect the 'Nouvelle Révolution' had on the lives of individual Masons. To set the scene and to put the role of Freemasonry into perspective in the life of France and the French political system, the origins of French Freemasonry are examined and explained. The main French Masonic obediences are discussed and the differences between them emphasised. The particular attributes of a Freemason are described and the ideals and ethos of the Order is discussed. From its earliest days, Freemasonry has often been persecuted by the Roman Catholic Church or by extreme Right-wing movements. The history of this persecution is reviewed and the reasons for its persistence noted, with especial emphasis on the treatment of Freemasons under the fascist regimes of Italy and Germany. The fate of Freemasonry in countries under German control is also briefly examined. With the occupation of France by the Germans, the differences and similarities of the treatment of French and German Freemasons are discussed. The processes and legislation of this ban are closely examined and the part played by the Vichy government in the persecution of French Freemasonry is discussed. The effects of this persecution and the consequences for individuals are examined and the Freemason's role in the emerging Resistance movement is reviewed. The contribution of many lodges to the Resistance movement is examined and the sacrifice of many Freemasons for their ideals is emphasised.

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A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

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This article analyzes the role of expert witness testimony in the trials of social movement actors, discussing the trial of the "Kingsnorth Six" in Britain and the trials of activists currently mobilising against airport construction at Notre Dame des Landes in western France. Though the study of expert testimony has so far overwhelmingly concentrated on fact-finding and admissibility, the cases here reveal the importance of expert testimony not simply in terms of legal argument, but in "moral" or political terms, as it reflects and constitutes movement cognitive praxis. In the so-called climate change defence presented by the Kingsnorth Six, I argue that expert testimony attained a "negotiation of proximity," connecting different types of contributory expertise to link the scales and registers of climate science with those of everyday understanding and meaning. Expert testimony in the trials of activists in France, however, whilst ostensibly able to develop similar bridging narratives, has instead been used to construct resistance to the airport siting as already proximate, material, and embedded. To explain this, I argue that attention to the symbolic, as well as instrumental, functions of expert testimony reveals the crucial role that collective memory plays in the construction of both knowledge and grievance in these cases. Collective memory is both a constraint on and catalyst for mobilisation, defining the boundaries of the sayable. Testimony in trials both reflects and reproduces these elements and is a vital explanatory tool for understanding the narrativisation and communication of movement identities and objectives. © 2013 The Author. Law & Policy © 2013 The University of Denver/Colorado Seminary.

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Elevated free fatty acids (FFA) are a feature of ageing and a risk factor for metabolic disorders such as cardiovascular disease (CVD) and type-2 diabetes (T2D). Elevated FFA contribute to insulin resistance, production of inflammatory cytokines and expression of adhesion molecules on immune cells and endothelial cells, risk factors for CVD and T2D. Molecular mechanisms of FFA effects on monocyte function and how FFA phenotype is affected by healthy ageing remain poorly understood. This thesis evaluated the effects of the two major FFA in plasma, oleate and palmitate on monocyte viability, cell surface antigen expression, and inflammatory activation in THP-1 monocytes. Palmitate but not oleate increased cell surface expression of CD11b and CD36 after 24h, independent of mitochondrial superoxide, but dependent on de novo synthesis of ceramides. LPS-mediated cytokine production in THP-1 monocytes was enhanced and decreased following incubation with palmitate and oleate respectively. In a model of monocyte-macrophage differentiation, palmitate induced a pro-inflammatory macrophage phenotype which required de novo ceramide synthesis, whilst oleate reduced cytokine secretion, producing a macrophage with enhanced clearance apoptotic cells. Plasma fatty acid analysis in young and mid-life populations revealed age-related increases in both the SFA and MUFA classes, especially the medium and very long chain C14 and C24 fatty acids, which were accompanied by increases in the estimated activities of desaturase enzymes. Changes were independently correlated with increased PBMC CD11b, plasma TNF-a and insulin resistance. In conclusion, the pro-atherogenic phenotype, enhanced LPS responses in monocytes, and pro-inflammatory macrophage in the presence of palmitate but not oleate is reliant upon de novo ceramide synthesis. Age-related increases in inflammation, cell surface integrin expression are related to increases in both the MUFA and SFA fatty acids, which in part may be explained by altered de novo fatty acid synthesis.

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Tissue transglutaminase (TG2) has been suggested to be a key player in the progression and metastasis of chemoresistant breast cancer. One of the foremost survival signalling pathways implicated in causing drug resistance in breast cancer is the constitutive activation of NFκB (Nuclear Factor -kappa B) induced by TG2. This study provides a mechanism by which TG2 constitutively activates NFκB which in turn confers chemoresistance to breast cancer cells against doxorubicin. Breast cancer cell lines with varying expression levels of TG2 as well as TG2 null breast cancer cells transfected with TG2 were used as the major cell models for this study. This study made use of cell permeable and impermeable TG2 inhibitors, specific TG2 and Rel A/ p65 targeting siRNA, TG2 functional blocking antibodies, IKK inhibitors and a specific targeting peptide against Rel A/p65 to investigate the pathway of activation involved in the constitutive activation of NFκB by TG2 leading to drug resistance. Crucial to the activation of Rel A/p65 and drug resistance in the breast cancer cells is the interaction between the complex of IκBα and Rel A/p65 with TG2 which results in the dimerization of Rel A/p65 and polymerization of IκBα. The association of TG2 with the IκBα-NFκB complex was determined to be independent of IKKα/β function. The polymerized IκBα is degraded in the cytoplasm by the μ-calpain pathway which allows the cross linked Rel A/ p65 dimers to translocate into the nucleus. Using R283 and ZDON (cell permeable TG2 activity inhibitors) and specific TG2 targeting siRNA, the Rel A/ p65 dimer formation could be inhibited. Co-immunoprecipitation studies confirmed that the phosphorylation of the Rel A/p65 dimers at the Ser536 residue by IKKε took place in the cell nucleus. Importantly, this study also investigated the transcriptional regulation of the TGM2 gene by the pSer536 Rel A/ p65 dimer and the importance of this TG2-NFκB feedback loop in conferring drug resistance to breast cancer cells. This data provides evidence that TG2 could be a key therapeutic target in the treatment of chemoresistant breast cancer.

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Two of the greatest crises that civilisation faces in the 21st century are the predicted rapid increases in the ageing population and levels of metabolic disorders such as obesity and type 2 diabetes. A growing amount of evidence now supports the notion that energy balance is a key determinant not only in metabolism but also in the process of cellular ageing. Much of genetic evidence for a metabolic activity-driven ageing process has come from model organisms such as worms and flies where inactivation of the insulin receptor signalling cascade prolongs lifespan. At its most simplistic, this poses a conundrum for ageing in humans – can reduced insulin receptor signalling really promote lifespan and does this relate to insulin resistance seen in ageing? In higher animals, caloric restriction studies have confirmed a longer lifespan when daily calorie intake is reduced to 60% of normal energy requirement. This suggests that for humans, it is energy excess which is a likely driver of metabolic ageing. Interventions that interfere with the metabolic fate of nutrients offer a potentially important target for delaying biological ageing.

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A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

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Modern comprehensive high schools do not formally track students into different programs, but schools offer different curricular sequences with important and stratified consequences for students' post-secondary education. This study used qualitative methodology to examine how schools' organizational cultures influence the maintenance of tracking practices in four comprehensive high schools in Miami. The methodology included long-term participant observation in each of the four schools, unstructured and semi-structured interviews and the collection of written documents produced by the district. A framework based on the concepts of environment, mission, information, strategy, and leadership was used to analyze the data. ^ It was found that school cultures shared deeply held beliefs that regard ability as a fixed trait. This prevented schools from providing access to information about the consequences of course selection to the majority of the student body, with the exception of those students defined as “college bound.” State and County level policies that reward achievement in standardized tests combined with school overcrowding, resulted in organizational cultures that favored the adoption of strategies stressing efficiency, as opposed to a challenging education for all students. Only one of the four schools in the study had a policy requiring students to attempt courses that were more challenging. The practice was resented by both teachers and counselors, since it was perceived as interfering with other goals of the institution, i.e.: graduating students in four years. ^ The culture of the schools stressed college as the only legitimate post-secondary option; consequently, the majority of counselors did not encourage students—even those already defined as “not college material”—to consider other alternatives, such as vocational education. The elimination of formal tracks in these comprehensive high schools resulted in the school culture lacking a clear mission in regards to non-college bound students. Findings are discussed in relation to current theoretical explanations for educational policy and equality of opportunity. ^

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In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAOΔampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.