Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa

Virulence of the opportunistic pathogen Pseudomonas aeruginosa involves the coordinate expression of a wide range of virulence factors including type IV pili which are required for colonization of host tissues and are associated with a form of surface translocation termed twitching motility. Twitching motility in P. aeruginosa is controlled by a complex signal transduction pathway which shares many modules in common with chemosensory systems controlling flagella rotation in bacteria and which is composed, in part, of the previously described proteins PilG, PilH, PilI, PilJ and PilK. Here we describe another three components of this pathway: ChpA, ChpB and ChpC, as well as two downstream genes, ChpD and ChpE, which may also be involved. The central component of the pathway, ChpA, possesses nine potential sites of phosphorylation: six histidine-containing phosphotransfer (HPt) domains, two novel serine- and threonine-containing phosphotransfer (SPt, TPt) domains and a CheY-like receiver domain at its C-terminus, and as such represents one of the most complex signalling proteins yet described in nature. We show that the Chp chemosensory system controls twitching motility and type IV pili biogenesis through control of pili assembly and/or retraction as well as expression of the pilin subunit gene pilA. The Chp system is also required for full virulence in a mouse model of acute pneumonia.

Treatment of naphthalene-2-sulfonic acid from tannery wastewater by a granular activated carbon fixed bed inoculated with bacterial isolates Arthrobacter globiformis and Comamonas testosteroni

The kinetics of naphthalene-2-sulfonic acid (2-NSA) adsorption by granular activated carbon (GAC) were measured and the relationships between adsorption, desorption, bioavailability and biodegradation assessed. The conventional Langmuir model fitted the experimental sorption isotherm data and introduced 2-NSA degrading bacteria, established on the surface of the GAC, did not interfere with adsorption. The potential value of GAC as a microbial support in the aerobic degradation of 2-NSA by Arthrobacter globiformis and Comamonas testosteroni was investigated. Using both virgin and microbially colonised GAC, adsorption removed 2-NSA from the liquid phase up to its saturation capacity of 140 mg/g GAC within 48 h. However, between 83.2% and 93.3% of the adsorbed 2-NSA was bioavailable to both bacterial species as a source of carbon for growth. In comparison to the non-inoculated GAC, the combination of rapid adsorption and biodegradation increased the amount (by 70–93%) of 2-NSA removal from the influent phase as well as the bed-life of the GAC (from 40 to >120 d). A microbially conditioned GAC fixed-bed reactor containing 15 g GAC removed 100% 2-NSA (100 mg/l) from tannery wastewater at an empty bed contact time of 22 min for a minimum of 120 d without the need for GAC reconditioning or replacement. This suggests that small volume GAC bioreactors could be used for tannery wastewater recycling.

A INFLUÊNCIA DAS PR��TICAS PEDAGÓGICAS DOCENTES E DAS BARREIRAS DISCENTES SOBRE O DESENVOLVIMENTO DA CRIATIVIDADE DO FUTURO ADMINISTRADOR

As empresas que almejam garantir e melhorar sua posição dentro de em um mercado cada vez mais competitivo precisam estar sempre atualizadas e em constante evolução. Na busca contínua por essa evolução, investem em projetos de Pesquisa & Desenvolvimento (P&D) e em seu capital humano para promover a criatividade e a inovação organizacional. As pessoas têm papel fundamental no desenvolvimento da inovação, mas para que isso possa florescer de forma constante é preciso comprometimento e criatividade para a geração de ideias. Criatividade é pensar o novo; inovação é fazer acontecer. Por��m, encontrar pessoas com essas qualidades nem sempre é tarefa fácil e muitas vezes é preciso estimular essas habilidades e caracter��sticas para que se tornem efetivamente criativas. Os cursos de graduação podem ser uma importante ferramenta para trabalhar esses aspectos, caracter��sticas e habilidades, usando métodos e pr��ticas de ensino que auxiliem no desenvolvimento da criatividade, pois o ambiente ensino-aprendizagem pesa significativamente na formação das pessoas. O objetivo deste estudo é de identificar quais fatores têm maior influência sobre o desenvolvimento da criatividade em um curso de graduação em administração, analisando a influência das pr��ticas pedagógicas dos docentes e as barreiras internas dos discentes. O referencial teórico se baseia principalmente nos trabalhos de Alencar, Fleith, Torrance e Wechsler. A pesquisa transversal de abordagem quantitativa teve como público-alvo os alunos do curso de Administração de uma universidade confessional da Grande São Paulo, que responderam 465 questionários compostos de tr��s escalas. Para as pr��ticas docentes foi adaptada a escala de Pr��ticas Docentes em relação à Criatividade. Para as barreiras internas foi adaptada a escala de Barreiras da Criatividade Pessoal. Para a análise da percepção do desenvolvimento da criatividade foi construída e validada uma escala baseada no referencial de caracter��sticas de uma pessoa criativa. As análises estatísticas descritivas e fatoriais exploratórias foram realizadas no software Statistical Package for the Social Sciences (SPSS), enquanto as análises fatoriais confirmatórias e a mensuração da influência das pr��ticas pedagógicas e das barreiras internas sobre a percepção do desenvolvimento da criatividade foram realizadas por modelagem de equação estrutural utilizando o algoritmo Partial Least Squares (PLS), no software Smart PLS 2.0. Os resultados apontaram que as pr��ticas pedagógicas e as barreiras internas dos discentes explicam 40% da percepção de desenvolvimento da criatividade, sendo as pr��ticas pedagógicas que exercem maior influencia. A pesquisa também apontou que o tipo de temática e o per��odo em que o aluno está cursando não têm influência sobre nenhum dos tr��s construtos, somente o professor influencia as pr��ticas pedagógicas.

ANALISANDO A RELAÇÃO DOS VOLUMES DE EXPORTAÇÃO E DE IMPORTAÇÃO, PIB, TAXAS DE CÂMBIO E INFLAÇÃO NO PER��ODO DE 2004 A 2014. SÃO BERNARDO DO CAMPO 2015

As empresas que almejam garantir e melhorar sua posição dentro de em um mercado cada vez mais competitivo precisam estar sempre atualizadas e em constante evolução. Na busca contínua por essa evolução, investem em projetos de Pesquisa & Desenvolvimento (P&D) e em seu capital humano para promover a criatividade e a inovação organizacional. As pessoas têm papel fundamental no desenvolvimento da inovação, mas para que isso possa florescer de forma constante é preciso comprometimento e criatividade para a geração de ideias. Criatividade é pensar o novo; inovação é fazer acontecer. Por��m, encontrar pessoas com essas qualidades nem sempre é tarefa fácil e muitas vezes é preciso estimular essas habilidades e caracter��sticas para que se tornem efetivamente criativas. Os cursos de graduação podem ser uma importante ferramenta para trabalhar esses aspectos, caracter��sticas e habilidades, usando métodos e pr��ticas de ensino que auxiliem no desenvolvimento da criatividade, pois o ambiente ensino-aprendizagem pesa significativamente na formação das pessoas. O objetivo deste estudo é de identificar quais fatores têm maior influência sobre o desenvolvimento da criatividade em um curso de graduação em administração, analisando a influência das pr��ticas pedagógicas dos docentes e as barreiras internas dos discentes. O referencial teórico se baseia principalmente nos trabalhos de Alencar, Fleith, Torrance e Wechsler. A pesquisa transversal de abordagem quantitativa teve como público-alvo os alunos do curso de Administração de uma universidade confessional da Grande São Paulo, que responderam 465 questionários compostos de tr��s escalas. Para as pr��ticas docentes foi adaptada a escala de Pr��ticas Docentes em relação à Criatividade. Para as barreiras internas foi adaptada a escala de Barreiras da Criatividade Pessoal. Para a análise da percepção do desenvolvimento da criatividade foi construída e validada uma escala baseada no referencial de caracter��sticas de uma pessoa criativa. As análises estatísticas descritivas e fatoriais exploratórias foram realizadas no software Statistical Package for the Social Sciences (SPSS), enquanto as análises fatoriais confirmatórias e a mensuração da influência das pr��ticas pedagógicas e das barreiras internas sobre a percepção do desenvolvimento da criatividade foram realizadas por modelagem de equação estrutural utilizando o algoritmo Partial Least Squares (PLS), no software Smart PLS 2.0. Os resultados apontaram que as pr��ticas pedagógicas e as barreiras internas dos discentes explicam 40% da percepção de desenvolvimento da criatividade, sendo as pr��ticas pedagógicas que exercem maior influencia. A pesquisa também apontou que o tipo de temática e o per��odo em que o aluno está cursando não têm influência sobre nenhum dos tr��s construtos, somente o professor influencia as pr��ticas pedagógicas.

Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis

OBJECTIVES: To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences, and costs. DESIGN: Randomised controlled trial. SETTING: Eight general practices in south Birmingham. PARTICIPANTS: 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg. INTERVENTIONS: Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice). MAIN OUTCOME MEASURES: Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences of method of blood pressure monitoring, and costs. RESULTS: 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (- 1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (251 pounds sterling (437 dollars; 364 euros) (95% confidence interval 233 pounds sterling to 275 pounds sterling) versus 240 pounds sterling (217 pounds sterling to 263 pounds sterling). CONCLUSIONS: Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care.

Comparison of estimates and calculations of risk of coronary heart disease by doctors and nurses using different calculation tools in general practice: cross sectional study

OBJECTIVE: To assess the effect of using different risk calculation tools on how general practitioners and practice nurses evaluate the risk of coronary heart disease with clinical data routinely available in patients' records. DESIGN: Subjective estimates of the risk of coronary heart disease and results of four different methods of calculation of risk were compared with each other and a reference standard that had been calculated with the Framingham equation; calculations were based on a sample of patients' records, randomly selected from groups at risk of coronary heart disease. SETTING: General practices in central England. PARTICIPANTS: 18 general practitioners and 18 practice nurses. MAIN OUTCOME MEASURES: Agreement of results of risk estimation and risk calculation with reference calculation; agreement of general practitioners with practice nurses; sensitivity and specificity of the different methods of risk calculation to detect patients at high or low risk of coronary heart disease. RESULTS: Only a minority of patients' records contained all of the risk factors required for the formal calculation of the risk of coronary heart disease (concentrations of high density lipoprotein (HDL) cholesterol were present in only 21%). Agreement of risk calculations with the reference standard was moderate (kappa=0.33-0.65 for practice nurses and 0.33 to 0.65 for general practitioners, depending on calculation tool), showing a trend for underestimation of risk. Moderate agreement was seen between the risks calculated by general practitioners and practice nurses for the same patients (kappa=0.47 to 0.58). The British charts gave the most sensitive results for risk of coronary heart disease (practice nurses 79%, general practitioners 80%), and it also gave the most specific results for practice nurses (100%), whereas the Sheffield table was the most specific method for general practitioners (89%). CONCLUSIONS: Routine calculation of the risk of coronary heart disease in primary care is hampered by poor availability of data on risk factors. General practitioners and practice nurses are able to evaluate the risk of coronary heart disease with only moderate accuracy. Data about risk factors need to be collected systematically, to allow the use of the most appropriate calculation tools.

Hydrophobicity and surface electrostatic charge of conidia of the mycoparasite Coniothyrium minitans

The effect of increasing culture age on cell surface hydrophobicity (CSH) and cell surface electrostatic charge (measured as zeta potential) of conidia from five isolates of Coniothyrium minitans representing three different morphological types was examined. Conidial CSH of three isolates (A2 960/1, CH1 and CH2) decreased with culture age, whereas CSH of two others (B 1300/2 and IMI 134523) remained high for the whole 42 day experimental period. In contrast, cell surface electrostatic charge decreased uniformly in conidia of all five isolates for the first 34 d and then rose slightly at 42 d. The variation in cell surface electrostatic charge (spectrum width) of the sampled conidia decreased with age for all five isolates. In all five isolates cell surface electrostatic charge of conidia became increasingly negative as the pH of the buffer used to suspend conidia was increased from pH 3.0 to 9.0. No relationship between colony morphology of C. minitans and conidial CSH and cell surface electrostatic charge was found.

The pH-induced swelling and collapse of a polybase brush synthesized by atom transfer radical polymerization

We have used neutron reflectometry to characterize the swelling behaviour of brushes of poly[2-(diethyl amino)ethyl methacrylate], a polybase, as a function of pH. The brushes, synthesized by the "grafting from" method of atom transfer radical polymerization, were observed to approximately double their thickness in low pH solutions, although the pK is shifted to a lower pH than in dilute solution. The composition-depth profile obtained from the reflectometry experiments for the swollen brushes reveals a region depleted in polymer between the substrate and the extended part of the brush.

CD4+ T cell surface alpha enolase is lower in older adults

To identify novel cell ageing markers in order to gain insight into ageing mechanisms, we adopted membrane enrichment and comparison of the CD4+ T cell membrane proteome (purified by cell surface labelling using Sulfo-NHS-SS-Biotin reagent) between healthy young (n=9, 20-25y) and older (n=10; 50-70y) male adults. Following two-dimensional gel electrophoresis (2DE) to separate pooled membrane proteins in triplicates, the identity of protein spots with age-dependent differences (p<0.05 and >1.4 fold difference) was determined using liquid chromatography-mass spectrometry (LC-MS/MS). Seventeen protein spot density differences (ten increased and seven decreased in the older adult group) were observed between young and older adults. From spot intensity analysis, CD4+ T cell surface α-enolase was decreased in expression by 1.5 fold in the older age group; this was verified by flow cytometry (n=22) and qPCR with significantly lower expression of cellular α-enolase mRNA and protein compared to young adult CD4+ T cells (p<0.05). In an independent age-matched case-control study, lower CD4+ T cell surface α-enolase expression was observed in age-matched patients with cardiovascular disease (p<0.05). An immune-modulatory role has been proposed for surface α-enolase and our findings of decreased expression suggest that deficits in surface α-enolase merit investigation in the context of immune dysfunction during ageing and vascular disease.

Essays on Competition in the Pharmaceutical Industry

Chapter 1: Patents and Entry Competition in the Pharmaceutical Industry: The Role of Marketing Exclusivity Effective patent length for innovation drugs is severely curtailed because of extensive efficacy and safety tests required for FDA approval, raising concern over adequacy of incentives for new drug development. The Hatch-Waxman Act extends patent length for new drugs by five years, but also promotes generic entry by simplifying approval procedures and granting 180-day marketing exclusivity to a first generic entrant before the patent expires. In this paper we present a dynamic model to examine the effect of marketing exclusivity. We find that marketing exclusivity may be redundant and its removal may increase generic firms' profits and social welfare. Chapter 2: Why Authorized Generics?: Theoretical and Empirical Investigations Facing generic competition, the brand-name companies some-times launch generic versions themselves called authorized generics. This practice is puzzling. If it is cannibalization, it cannot be profitable. If it is divisionalization, it should be practiced always instead of sometimes. I explain this phenomenon in terms of switching costs in a model in which the incumbent first develops a customer base to ready itself against generic competition later. I show that only sufficiently low switching costs or large market size justifies launch of AGs. I then use prescription drug data to test those results and find support. Chapter 3: The Merger Paradox and R&D Oligopoly theory says that merger is unprofitable, unless a majority of firms in industry merge. Here, we introduce R&D opportunities to resolve this so-called merger paradox. We have three results. First, when there is one R&D firm, that firm can profitably merge with any number of non-R&D firms. Second, with multiple R&D firms and multiple non-R&D firms, all R&D firms can profitably merge. Third, with two R&D firms and two non-R&D firms, each R&D firms prefer to merge with a non-R&D firm. With three or more than non-R&D firms, however, the R&D firms prefer to merge with each other.

Compilation of growth rate data for marine pelagic organisms

The metabolic rate of organisms may either be viewed as a basic property from which other vital rates and many ecological patterns emerge and that follows a universal allometric mass scaling law; or it may be considered a property of the organism that emerges as a result of the organism's adaptation to the environment, with consequently less universal mass scaling properties. Data on body mass, maximum ingestion and clearance rates, respiration rates and maximum growth rates of animals living in the ocean epipelagic were compiled from the literature, mainly from original papers but also from previous compilations by other authors. Data were read from tables or digitized from graphs. Only measurements made on individuals of know size, or groups of individuals of similar and known size were included. We show that clearance and respiration rates have life-form-dependent allometries that have similar scaling but different elevations, such that the mass-specific rates converge on a rather narrow size-independent range. In contrast, ingestion and growth rates follow a near-universal taxa-independent ~3/4 mass scaling power law. We argue that the declining mass-specific clearance rates with size within taxa is related to the inherent decrease in feeding efficiency of any particular feeding mode. The transitions between feeding mode and simultaneous transitions in clearance and respiration rates may then represent adaptations to the food environment and be the result of the optimization of tradeoffs that allow sufficient feeding and growth rates to balance mortality.

Surface Ocean CO2 Atlas (SOCAT) V1.4

A well-documented, publicly available, global data set of surface ocean carbon dioxide (CO2) parameters has been called for by international groups for nearly two decades. The Surface Ocean CO2 Atlas (SOCAT) project was initiated by the international marine carbon science community in 2007 with the aim of providing a comprehensive, publicly available, regularly updated, global data set of marine surface CO2, which had been subject to quality control (QC). Many additional CO2 data, not yet made public via the Carbon Dioxide Information Analysis Center (CDIAC), were retrieved from data originators, public websites and other data centres. All data were put in a uniform format following a strict protocol. Quality control was carried out according to clearly defined criteria. Regional specialists performed the quality control, using state-of-the-art web-based tools, specially developed for accomplishing this global team effort. SOCAT version 1.5 was made public in September 2011 and holds 6.3 million quality controlled surface CO2 data points from the global oceans and coastal seas, spanning four decades (1968-2007). Three types of data products are available: individual cruise files, a merged complete data set and gridded products. With the rapid expansion of marine CO2 data collection and the importance of quantifying net global oceanic CO2 uptake and its changes, sustained data synthesis and data access are priorities.