Hepatic disposition and metabolite kinetics of a homologous series of diflunisal esters

The hepatic disposition and metabolite kinetics of a homologous series of diflunisal O-acyl esters (acetyl, butanoyl, pentanoyl, anti hexanoyl) were determined using a single-pass perfused in situ rat liver preparation. The experiments were conducted using 2% BSA Krebs-Henseleit buffer (pH 7.4), and perfusions were performed at 30 mL/min in each liver. O-Acyl esters of diflunisal and pregenerated diflunisal were injected separately into the portal vein. The venous outflow samples containing the esters and metabolite diflunisal were analyzed by high performance liquid chromatography (HPLC). The normalized outflow concentration-time profiles for each parent ester and the formed metabolite, diflunisal, were analyzed using statistical moments analysis and the two-compartment dispersion model. Data (presented as mean +/- standard error for triplicate experiments) was compared using ANOVA repeated measures, significance level P < 0.05. The hepatic availability (AUC'), the fraction of the injected dose recovered in the outflowing perfusate, for O-acetyldiflunisal (C2D = 0.21 +/- 0.03) was significantly lower than the other esters (0.34-0.38). However, R-N/f(u), the removal efficiency number R-N divided by the unbound fraction in perfusate f(u), which represents the removal efficiency of unbound ester by the liver, was significantly higher for the most lipophilic ester (O-hexanoyldiflunisal, C6D = 16.50 +/- 0.22) compared to the other members of the series (9.57 to 11.17). The most lipophilic ester, C6D, had the largest permeability surface area (PS) product (94.52 +/- 38.20 mt min-l g-l liver) and tissue distribution value VT (35.62 +/- 11.33 mL g(-1) liver) in this series. The MTT of these O-acyl esters of diflunisal were not significantly different from one another. However, the metabolite diflunisal MTTs tended to increase with the increase in the parent ester lipophilicity (11.41 +/- 2.19 s for C2D to 38.63 +/- 9.81 s for C6D). The two-compartment dispersion model equations adequately described the outflow profiles for the parent esters and the metabolite diflunisal formed from the O-acyl esters of diflunisal in the liver.

Structured modeling of recombinant protein production in batch and fed-batch culture of baculovirus-infected insect cells

The infection of insect cells with baculovirus was described in a mathematical model as a part of the structured dynamic model describing whole animal cell metabolism. The model presented here is capable of simulating cell population dynamics, the concentrations of extracellular and intracellular viral components, and the heterologous product titers. The model describes the whole processes of viral infection and the effect of the infection on the host cell metabolism. Dynamic simulation of the model in batch and fed-batch mode gave good agreement between model predictions and experimental data. Optimum conditions for insect cell culture and viral infection in batch and fed-batch culture were studied using the model.

Deconvolving the delta O-18 seawater component from subseasonal coral delta O-18 and Sr/Ca at Rarotonga in the southwestern subtropical Pacific for the period 1726 to 1997

To reconstruct oceanographic variations in the subtropical South Pacific, 271-year long subseasonal time series of Sr/Ca and delta(18)O were generated from a coral growing at Rarotonga (21.5degreesS, 159.5degreesW). In this case, coral Sr/Ca appears to be an excellent proxy for sea surface temperature (SST) and coral delta(18)O is a function of both SST and seawater delta(18)O composition (delta(18)O(sw)). Here, we focus on extracting the delta(18)O(sw) signal from these proxy records. A method is presented assuming that coral Sr/Ca is solely a function of SST and that coral delta(18)O is a function of both SST and delta(18)O(sw). This method separates the effects of delta(18)O(sw) from SST by breaking the instantaneous changes of coral delta(18)O into separate contributions by instantaneous SST and delta(18)O(sw) changes, respectively. The results show that on average delta(18)O(sw) at Rarotonga explains similar to39% of the variance in delta(18)O and that variations in SST explains the remaining similar to61% of delta(18)O variance. Reconstructed delta(18)O(sw) shows systematic increases in summer months (December-February) consistent with the regional pattern of variations in precipitation and evaporation. The delta(18)O(sw) also shows a positive linear correlation with satellite-derived estimated salinity for the period 1980 to 1997 (r = 0.72). This linear correlation between reconstructed delta(18)O(sw) and salinity makes it possible to use the reconstructed delta(18)O(sw) to estimate the past interannual and decadal salinity changes in this region. Comparisons of coral delta(18)O and delta(18)O(sw) at Rarotonga with the Pacific decadal oscillation index suggest that the decadal and interdecadal salinity and SST variability at Rarotonga appears to be related to basin-scale decadal variability in the Pacific. Copyright (C) 2002 Elsevier Science Ltd.

Physical function interfering with pain and symptoms in fibromyalgia patients

Objectives. The aim of this study was to assess the relationship between variables of physical assessment - muscular strength, flexibility and dynamic balance - with pain, pain threshold, and fibromyalgia symptoms (FM). Methods. Our sample consists of 55 women, with age ranging from 30 to 55 years (mean of 46.5, (standard deviation, SD=6.6)), mean body mass index (BMI) of 28.7(3.8) and diagnosed for FM according to the American College of Rheumatology criteria. Pain intensity was measured using a visual analogue scale (VAS) and pain threshold (PT) using Fisher`s dolorimeter. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ); flexibility by the third finger to floor test (3FF); the muscular strength index (MSI) by the maximum volunteer isometric contraction at flexion and extension of right knee and elbow using a force transducer, dynamic balance by the time to get up and go (TUG) test and the functional reach test (FRT). Data were analysed using Pearson`s correlation, as well as simple and multivariate regression tests, with significance level of 5%. Results. PT and FIQ were weakly but significantly correlated with the TUG, MSI and 3FF as well as VAS with the TUG and MSI (p<0.05). VAS, PT and FIQ was not correlated with FRT. Simple regression suggests that, alone, TUG, FR, MSI and 3FF are low predictors of VAS, PT and FIQ. For the VAS, the best predictive model includes TUG and MSI, explaining 12.6% of pain. variability. For TP and total symptoms, as obtained by the FIQ, most predictive model includes 3FF and MSI, which respectively respond by 30% and 21% of the variability. Conclusion. Muscular strength, flexibility and balance are associated with pain, pain threshold, and symptoms in FM patients.

Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Robust model-order reduction of complex biological processes

This paper addresses robust model-order reduction of a high dimensional nonlinear partial differential equation (PDE) model of a complex biological process. Based on a nonlinear, distributed parameter model of the same process which was validated against experimental data of an existing, pilot-scale BNR activated sludge plant, we developed a state-space model with 154 state variables in this work. A general algorithm for robustly reducing the nonlinear PDE model is presented and based on an investigation of five state-of-the-art model-order reduction techniques, we are able to reduce the original model to a model with only 30 states without incurring pronounced modelling errors. The Singular perturbation approximation balanced truncating technique is found to give the lowest modelling errors in low frequency ranges and hence is deemed most suitable for controller design and other real-time applications. (C) 2002 Elsevier Science Ltd. All rights reserved.

Conception of a flexible integrator and lean model for integrated management systems

Management systems standards (MSSs) have developed in an unprecedented manner in the last few years. These MSS cover a wide array of different disciplines, aims and activities of organisations. Also, organisations are populated with an enormous diversity of independent management systems (MSs). An integrated management system (IMS) tends to integrate some or all components of the business. Maximising their integration in one coherent and efficient MS is increasingly a strategic priority and constitutes an opportunity for businesses to be more competitive and consequently, promote its sustainable success. Those organisations that are quicker and more efficient in their integration and continuous improvement will have a competitive advantage in obtaining sustainable value in our global and competitive business world. Several scholars have proposed various theoretical approaches regarding the integration of management sub-systems, leading to the conclusion that there is no common practice for all organisations as they encompass different characteristics. One other author shows that several tangible and intangible gains for organisations, as well as to their internal and external stakeholders, are achieved with the integration of the individual standardised MSs. The purpose of this work was to conceive a model, Flexible, Integrator and Lean for IMSs, according to ISO 9001 for quality; ISO 14001 for environment and OHSAS 18001 for occupational health and safety (IMS–QES), that can be adapted and progressively assimilate other MSs, such as, SA 8000/ISO 26000 for social accountability, ISO 31000 for risk management and ISO/IEC 27001 for information security management, among others. The IMS–QES model was designed in the real environment of an industrial Portuguese small and medium enterprise, that over the years has been adopting, gradually, in whole or in part, individual MSSs. The developed model is based on a preliminary investigation conducted through a questionnaire. The strategy and research methods have taken into consideration the case study. Among the main findings of the survey we highlight: the creation of added value for the business through the elimination of several organisational wastes; the integrated management of the sustainability components; the elimination of conflicts between independent MS; dialogue with the main stakeholders and commitment to their ongoing satisfaction and increased contribution to the company’s competitiveness; and greater valorisation and motivation of employees as a result of the expansion of their skill base, actions and responsibilities, with their consequent empowerment. A set of key performance indicators (KPIs) constitute the support, in a perspective of business excellence, to the follow up of the organisation’s progress towards the vision and achievement of the defined objectives in the context of each component of the IMS model. The conceived model had many phases and the one presented in this work is the last required for the integration of quality, environment, safety and others individual standardised MSs. Globally, the investigation results, by themselves, justified and prioritised the conception of an IMS–QES model, to be implemented at the company where the investigation was conducted, but also a generic model of an IMS, which may be more flexible, integrator and lean as possible, potentiating the efficiency, added value both in the present and, fundamentally, for future.

A model updating technique based on FRFs for damped structures

Model updating methods often neglect that in fact all physical structures are damped. Such simplification relies on the structural modelling approach, although it compromises the accuracy of the predictions of the structural dynamic behaviour. In the present work, the authors address the problem of finite element (FE) model updating based on measured frequency response functions (FRFs), considering damping. The proposed procedure is based upon the complex experimental data, which contains information related to the damped FE model parameters and presents the advantage of requiring no prior knowledge about the damping matrix structure or its content, only demanding the definition of the damping type. Numerical simulations are performed in order to establish the applicability of the proposed damped FE model updating technique and its results are discussed in terms of the correlation between the simulated experimental complex FRFs and the ones obtained from the updated FE model.

Experimental Measurements and Correlation of the Solubility of Three Primary Amides in Supercritical CO2: Acetanilide, Propanamide, and Butanamide

Solubilities of three primary amides, namely, acetanilide, propanamide, and butanamide, in supercritical carbon dioxide were measured at T = (308.2, 313.2, and 323.2) K over the pressure range (9.0 to 40.0) MPa by a flow type apparatus. The solubility behavior of the three solids shows an analogous trend with a crossover region of the respective isotherms between (12 to 14) MPa. The solubility of each amide, at the same temperature and pressure, decreases from propanamide to acetanilide. Pure compound properties required for the modeling were estimated, and the solubilities of the amides were correlated by using the Soave-Redlich-Kwong cubic equation of state with an absolute average relative deviation (AARD) from (1.3 to 6.1) %.

Exposure to particles and fungi in Portuguese swine production

Versão preprint.

Climatic patterns and physical controls of chlorophyll-a in the Northeast Atlantic

Tese de Doutoramento, Física, 17 de Dezembro de 2013, Universidade dos Açores.

Explorador integrado de serviços de armazenamento na cloud: cloud cockpit

Projeto para obtenção do grau de Mestre em Engenharia Informática e de Computadores

Ensemble: an e-learning framework

E-Learning frameworks are conceptual tools to organize networks of elearning services. Most frameworks cover areas that go beyond the scope of e-learning, from course to financial management, and neglects the typical activities in everyday life of teachers and students at schools such as the creation, delivery, resolution and evaluation of assignments. This paper presents the Ensemble framework - an e-learning framework exclusively focused on the teaching-learning process through the coordination of pedagogical services. The framework presents an abstract data, integration and evaluation model based on content and communications specifications. These specifications must base the implementation of networks in specialized domains with complex evaluations. In this paper we specialize the framework for two domains with complex evaluation: computer programming and computer-aided design (CAD). For each domain we highlight two Ensemble hotspots: data and evaluations procedures. In the former we formally describe the exercise and present possible extensions. In the latter, we describe the automatic evaluation procedures.

Contributos do otimismo para a empregabilidade: boas práticas de acolhimento e integração

Foi no âmbito da realização da investigação, que tem como propósito geral contribuir para o conhecimento na área de Recursos Humanos, que efetuamos este estudo definindo como tema os contributos do Otimismo e Adaptabilidade para a Empregabilidade. Tem como objetos de estudo as práticas de Acolhimento & Integração das Pessoas no Grupo Valpi e de que forma o otimismo, reforça e se correlaciona com esse processo. Adicionalmente, procura avaliar o nível de empregabilidade dos seus colaboradores na sua dimensão da adaptabilidade pessoal, especialmente o papel do otimismo, tendo como base o modelo de Fugate, Kinicki e Ashforth (2004). A metodologia de investigação seguiu uma abordagem metodológica mista, por inquérito de pesquisa quantitativa e qualitativa, com recurso à utilização de instrumentos de recolha de dados, respetivamente, por questionário e por entrevista, utilizando a técnica de grupo de discussão focalizada. O questionário de escala de resposta do tipo Likert já existente, suportando o modelo de investigação proposto e as variáveis em estudo, foi aplicado a uma amostra intencional da população, por conveniência e aleatória. Foram inquiridos cem participantes por questionário e participaram cinco elementos no grupo de discussão focalizada, tendo sido neste caso escolhido uma amostra por conveniência e não aleatória, com interlocutores privilegiados da empresa. Os dados deste estudo permitem-nos concluir que o otimismo é uma variável relevante quer do ponto de vista da organização, quer do ponto de vista do individuo.

Development of biocompatible and “smart” porous structures using CO2-assisted processes

Dissertação apresentada para a obtenção do grau de Doutor em Engenharia Química, especialidade Engenharia da Reacção Química, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia