The inhibitory activity of synthetic compounds and ions against transporters of multi-drug resistant bacteria

RESUMO: Sessenta e três derivados de hidantoína foram utilizados para avaliar possíveis efeitos de modulação na actividade das bombas de efluxo (BE) na Salmonella NCTC 13349 utilizando um método fluorimétrico semi-automático. Nenhum dos compostos apresentaram actividade anti-bacteriana até concentrações de 240 mg/L. Entre todos os compostos, SZ-7 demonstrou possuir propriedades de modulação de effluxo na presença de glucose. Para testar esta actividade, estirpes de Salmonella resistentes à ciprofloxacina, induzidas a elevados níveis de resistência com sobre-expressão de BE, foram expostas ao SZ-7. Este derivado afectou a susceptibilidade das estirpes à ciprofloxacina. Uma vez que os 63 compostos estudados apresentaram pouco efeito inibitório /cumulativo, apesar de serem conhecidos pelos seus efeitos moduladores de BE-dependentes de iões em eucariotas, foi questionado o papel dos iões na regulação de BE bacterianas, que poderão influenciar a eficácia de novos compostos. Para este estudo, utilizamos a Escherichia coli AG100 como modelo, devido ao extenso conhecimento no que respeita a estrutura e actividade das BE. Devido à importância de iões de cálcio (Ca2+) nos canais de transporte membranar e na actividade de ATPases, a sua actividade na modulação do efluxo foi investigada. De resultados anteriormente obtidos concluiu-se que a pH 5 o efluxo é independente de energia metabólica; contudo, a pH 8 é absolutamente dependente, sendo que o Ca2+ é indispensável para manter a actividade das ATPases bacterianas. A acumulação/effluxo de EtBr pela E. coli AG100 foi determinada na presença/ausência de Ca2+, clorpromazina (inibidor de ligação de Ca2+ a proteínas), e ácido etilenodiamino tetra-acético (quelante de Ca2+). Acumulação/effluxo aumentou a pH 8, contudo o Ca2+ reverte estes efeitos evidenciando a sua importância no funcionamento das BE bacterianas. Em resumo este trabalho colocou em evidência que muitos aspectos bioquímicos e bioenergéticos devem ser tomados em consideração no estudo da resistência bacteriana mediada por BE.------- ABSTRACT: Sixty-three hydantoin derivatives were evaluated for their modulating effects on efflux pump (EP) activity of Salmonella NCTC 13349 utilizing a semi-automatic fluorometric method. None of the compounds presented antibacterial activities at concentrations as high as 240 mg/L. Among all compounds, SZ-7 showed possible efflux modulating activity in the presence of glucose, indicative of a potential EP inhibitor. To verify its potential effects, ciprofloxacin-resistant Salmonella strains, induced to high level resistance with over-expressing EPs, were exposed to SZ-7. This derivative affected the susceptibility of the ciprofloxacin-resistant strains. Since the 63 compounds studied had very low inhibitory/accumulative effects, even though their known for being efficient in modulating ion-driven eukaryotic EPs, we questioned whether ions had a leading role in regulating bacterial EPs, influencing the effectiveness of new compounds. For this study we used Escherichia coli AG100 as a model, due to the extensive knowledge on its EPs structure and activity. Owing the importance of calcium ions (Ca2+) for membrane transport channels and activity of ATPases, the role of Ca2+ was investigated. From previous results we concluded that at pH 5 efflux is independent of metabolic energy; however, at pH 8 it is entirely dependent of metabolic energy and the Ca2+ ions are essential to maintain the activity of bacterial ATPases. Accumulation and efflux of ethidium bromide (EtBr) by E. coli AG100 was determined in the presence and absence of Ca2+, chlorpromazine (inhibitor of Ca2+-binding to proteins), and ethylenediaminetetraacetic acid (Ca2+ chelator). Accumulation of EtBr increased at pH 8; however Ca2+ reversed these effects providing information as to the importance of this ion in the regulation of bacterial EP systems. Overall this work puts in evidence that many biochemical and bioenergetic aspects related to the strains physiology need to be taken into consideration in bacterial drug resistance mediated by EPs.

Performance of state space and ARIMA models for consumer retail sales forecasting

Forecasting future sales is one of the most important issues that is beyond all strategic and planning decisions in effective operations of retail businesses. For profitable retail businesses, accurate demand forecasting is crucial in organizing and planning production, purchasing, transportation and labor force. Retail sales series belong to a special type of time series that typically contain trend and seasonal patterns, presenting challenges in developing effective forecasting models. This work compares the forecasting performance of state space models and ARIMA models. The forecasting performance is demonstrated through a case study of retail sales of five different categories of women footwear: Boots, Booties, Flats, Sandals and Shoes. On both methodologies the model with the minimum value of Akaike's Information Criteria for the in-sample period was selected from all admissible models for further evaluation in the out-of-sample. Both one-step and multiple-step forecasts were produced. The results show that when an automatic algorithm the overall out-of-sample forecasting performance of state space and ARIMA models evaluated via RMSE, MAE and MAPE is quite similar on both one-step and multi-step forecasts. We also conclude that state space and ARIMA produce coverage probabilities that are close to the nominal rates for both one-step and multi-step forecasts.

Spatial distribution of dengue in the city of Cruzeiro, São Paulo State, Brazil: use of geoprocessing tools

The aim of this article is to identify patterns in spatial distribution of cases of dengue fever that occurred in the municipality of Cruzeiro, State of São Paulo, in 2006. This is an ecological and exploratory study using the tools of spatial analysis in the preparation of thematic maps with data from Sinan-Net. An analysis was made by area, taking as unit the IBGE census, the analysis included four months in 2006 which show the occurrence of the disease in the city. The thematic maps were constructed by TerraView 3.3.1 software, the same software provided the values of the indicators of Global Moran (I M) every month and the Kernel estimation. In the year 2006, 691 cases of dengue were georeferenced (with a rate of 864.2 cases/100,000 inhabitants); the indicators of Moran and p-values obtained were I M = 0.080 (March) p = 0.11; I M = 0.285 (April) p = 0.01; I M = 0.201 (May) p = 0.01 and I M = 0.002 (June) p = 0.57. The first cases were identified in the Northeast and Central areas of Cruzeiro and the recent cases, in the North, Northeast and Central. It was possible to identify census tracts where the epidemic began and how it occurred temporally and spatially in the city.

Automatic Small Bowel Tumor Diagnosis by Using Multi-Scale Wavelet-Based Analysis in Wireless Capsule Endoscopy Images

BACKGROUND: Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. METHOD: The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. RESULTS: The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.

Heat recovery from wastewater: numerical modelling of sewer systems

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente, perfil Engenharia Sanitária

A new CuZ active form in the catalytic reduction of N2O by nitrous oxide reductase from Pseudomonas nautica

J Biol Inorg Chem (2010) 15:967–976 DOI 10.1007/s00775-010-0658-6

A framework for semantic checking of information systems

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

An agent based architecture for material handling systems

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Recursive neuro fuzzy techniques for online identification and control

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Multi-GPU support on the marrow algorithmic skeleton framework

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Estimating data divergence in cloud computing storage systems

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

A constructive technology assessment of stationary energy storage systems: prospective life cycle orientated analysis

Based on the presentation and discussion at the 3rd Winter School on Technology Assessment, December 2012, Universidade Nova de Lisboa (Portugal), Caparica Campus, PhD programme on Technology Assessment

Healing replicas in a software component replication system

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Real-time labview assessment on adsorption systems

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

STRUCTURE-FUNCTION ANALYSIS OF MULTI-COPPER OXIDASES

Dissertation presented to obtain the Ph.D degree in Biochemistry, Structural Biochemistry