Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: Transmembrane exchange and cytoplasmic binding process

This work studied the structure-hepatic disposition relationships for cationic drugs of varying lipophilicity using a single-pass, in situ rat liver preparation. The lipophilicity among the cationic drugs studied in this work is in the following order: diltiazem. propranolol. labetalol. prazosin. antipyrine. atenolol. Parameters characterizing the hepatic distribution and elimination kinetics of the drugs were estimated using the multiple indicator dilution method. The kinetic model used to describe drug transport (the two-phase stochastic model) integrated cytoplasmic binding kinetics and belongs to the class of barrier-limited and space-distributed liver models. Hepatic extraction ratio (E) (0.30-0.92) increased with lipophilicity. The intracellular binding rate constant (k(on)) and the equilibrium amount ratios characterizing the slowly and rapidly equilibrating binding sites (K-S and K-R) increase with the lipophilicity of drug (k(on) : 0.05-0.35 s(-1); K-S : 0.61-16.67; K-R : 0.36-0.95), whereas the intracellular unbinding rate constant (k(off)) decreases with the lipophilicity of drug (0.081-0.021 s(-1)). The partition ratio of influx (k(in)) and efflux rate constant (k(out)), k(in)/k(out), increases with increasing pK(a) value of the drug [from 1.72 for antipyrine (pK(a) = 1.45) to 9.76 for propranolol (pK(a) = 9.45)], the differences in k(in/kout) for the different drugs mainly arising from ion trapping in the mitochondria and lysosomes. The value of intrinsic elimination clearance (CLint), permeation clearance (CLpT), and permeability-surface area product (PS) all increase with the lipophilicity of drug [CLint (ml . min(-1) . g(-1) of liver): 10.08-67.41; CLpT (ml . min(-1) . g(-1) of liver): 10.80-5.35; PS (ml . min(-1) . g(-1) of liver): 14.59-90.54]. It is concluded that cationic drug kinetics in the liver can be modeled using models that integrate the presence of cytoplasmic binding, a hepatocyte barrier, and a vascular transit density function.

A formal representation of assumptions in process modelling

In this work, we present a systematic approach to the representation of modelling assumptions. Modelling assumptions form the fundamental basis for the mathematical description of a process system. These assumptions can be translated into either additional mathematical relationships or constraints between model variables, equations, balance volumes or parameters. In order to analyse the effect of modelling assumptions in a formal, rigorous way, a syntax of modelling assumptions has been defined. The smallest indivisible syntactical element, the so called assumption atom has been identified as a triplet. With this syntax a modelling assumption can be described as an elementary assumption, i.e. an assumption consisting of only an assumption atom or a composite assumption consisting of a conjunction of elementary assumptions. The above syntax of modelling assumptions enables us to represent modelling assumptions as transformations acting on the set of model equations. The notion of syntactical correctness and semantical consistency of sets of modelling assumptions is defined and necessary conditions for checking them are given. These transformations can be used in several ways and their implications can be analysed by formal methods. The modelling assumptions define model hierarchies. That is, a series of model families each belonging to a particular equivalence class. These model equivalence classes can be related to primal assumptions regarding the definition of mass, energy and momentum balance volumes and to secondary and tiertinary assumptions regarding the presence or absence and the form of mechanisms within the system. Within equivalence classes, there are many model members, these being related to algebraic model transformations for the particular model. We show how these model hierarchies are driven by the underlying assumption structure and indicate some implications on system dynamics and complexity issues. (C) 2001 Elsevier Science Ltd. All rights reserved.

Process mineralogy of fluorosilicate minerals in OK Tedi ores

The impact of fluorine in copper flotation was relatively unknown until the introduction of skarn ores in the Ok Tedi concentrator. Fluorine in the copper concentrates reports to the gas phase during the smelting stage and forms a corrosive H2SO4-HCl-HF acid brine mixture which must be neutralised. This work was aimed at studying the mineralogy of the fluorosilicate minerals contained in the various oretypes present in the Ok Tedi porphyry copper deposit. The electron microprobe was used to analyse for fluorine and hence identify the fluorosilicate minerals in each oretype. This study revealed talc, phlogopite, biotite, clays, amphiboles, fluoroapatite and titanite to be the sources of fluorine in the orebody. Laboratory and plant investigations were conducted to study the flotation response of these minerals. Chemical assaying of the products of these tests was done to determine the bulk assay of fluorine, Using Rietveld analysis, quantitative estimates of the fluorosilicate minerals in these products were generated. Marrying of the bulk assay with the respective mineralogical assay enabled the understanding of the flotation behavior of fluorine and it's associated mineralogy. Talc and phlogopite were found to be the causes of the fluorine problem at Ok Tedi. (C) 2001 Elsevier Science Ltd. All rights reserved.

Client resistance in outreaching social work in Hong Kong

This paper reports the survey findings of a study on the outreaching social workers' perceptions of client resistance. In light of their social work practice 10th youth-at-risk in Hong Kong, resistance is generally recognised as a natural phenomenon in the counselling process and to a certain extent, is an obstacle to engaging in purposeful worker-client relationship as well as effecting behavioural changes. On Pipes and Davenport's (1990) classification, the respondents were more likely to classify client resistance as innocuous behaviours like missing appointments and refusing to discuss problems than disarming and proactive behaviours. The implications of these findings are discussed.

Work domain analysis and sensors II: Pasteurizer II case study

In this paper we use sensor-annotated abstraction hierarchies (Reising & Sanderson, 1996, 2002a,b) to show that unless appropriately instrumented, configural displays designed according to the principles of ecological interface design (EID) might be vulnerable to misinterpretation when sensors become unreliable or are unavailable. Building on foundations established in Reising and Sanderson (2002a) we use a pasteurization process control example to show how sensor-annotated AHs help the analyst determine the impact of different instrumentation engineering policies on a configural display that is part of an ecological interface. Our analyses suggest that configural displays showing higher-order properties of a system are especially vulnerable under some conservative instrumentation configurations. However, sensor-annotated AHs can be used to indicate where corrective instrumentation might be placed. We argue that if EID is to be effectively employed in the design of displays for complex systems, then the information needs of the human operator need to be considered while instrumentation requirements are being formulated. Rasmussen's abstraction hierarchy-and particularly its extension to the analysis of information captured by sensors and derived from sensors-may therefore be a useful adjunct to up-stream instrumentation design. (C) 2002 Elsevier Science Ltd. All rights reserved.

Exploring the interdisciplinary process in design education

The work presented herein follows an ongoing research that aims to analyze methodological practices to be applied in Design Education. A reflection about methodological strategies in Design Education and the function of drawing in Design represents the beginning of this study. Then, we developed an interdisciplinary pedagogical experience with the Graphic Design 1st grade students from our institution (IPCA). In the current academic year, 2013/2014, we continue to evolve this project, introducing changes in the initial proposal. Major alterations focused on the aspects that could be strengthened in terms of interdisciplinarity. In this article, the authors describe those changes and discuss the outcomes of the novel proposal. As we have already reported, this investigation follows a reflection about working methods to be adopted in Design Education. This is in accordance with other previously published works that purpose the enlargement of Design into new knowledge fields such as Experience or Service Design, changing not only the role of the graphic designer, but also the skills required to be a professional designer (Alain Findelli, 2001), (Brian Lawson, 2006), (Ciampa-Brewer, 2010). Furthermore, concepts such as cooperation or multidisciplinary design, amongst others, have been frequently debated as design teaching strategies (Heller and Talarico, 2011, pp. 82-85). These educational approaches also have an impact on our research. The analysis of all these authors’ contributions together with a reflection on our teaching practice allowed us to propose an improved interdisciplinary intervention.

Neoinstitutionalism and the appropriation of bourdieu's work: a critical assessment

Despite the still present hegemony of the structural-functionalist orthodoxy, the mid 1980's witnesses the insurgence of new philosophical approaches. This body of work had become a vital intellectual and ideological resource for those who wanted to confront the functionalist dominance in organization studies, such as structuration theory, labour process theory and neoinstitutionalist theory. The purpose of this paper is to review the incorporation of Bourdieu's work into neoinstitutionalism. I argue that this appropriation has resulted in a significant loss of theoretical strength. By giving place to the cognitivist metaphors of mental models, "scripts" and "schemas", instead of adopting the notion of habitus, neoinstitutionalism reinforces some of the ever-present dichotomies in social sciences, especially those of agency/structure and individual/society. While neoinstitutionalism was refining the cognitive approach in the 1990's, Bourdieu was moving towards psychoanalysis. Some indications for future research are provided in the concluding notes.

Innovation through virtual communities of Practice: motivation and constraints in the knowledge-creation process

Communities of Practice are places which provide a sound basis for organizational learning, enabling knowledge creation and acquisition thus improving organizational performance, leveraging innovation and consequently increasing competitively. Virtual Communities of Practice (VCoP‟s) can perform a central role in promoting communication and collaboration between members who are dispersed in both time and space. The ongoing case study, described here, aims to identify both the motivations and the constraints that members of an organization experience when taking part in the knowledge creating processes of the VCoP‟s to which they belong. Based on a literature review, we have identified several factors that influence such processes; they will be used to analyse the results of interviews carried out with the leaders of VCoP‟s in four multinationals. As future work, a questionnaire will be developed and administered to the other members of these VCoP‟s

CVD of CrO(2): Towards a lower temperature deposition process

The deposition of highly oriented a-axis CrO(2) films onto Al(2)O(3)(0001) by atmospheric pressure (AP)CVD at temperatures as low as 330 C is reported. Deposition rates strongly depend on the substrate temperature, whereas for film surface microstructures the dependence is mainly on film thickness. For the experimental conditions used in this work, CrO(2) growth kinetics are dominated by a surface reaction mechanism with an apparent activation energy of (121.0 +/- 4.3) kJ mol(-1). The magnitude and temperature dependence of the saturation magnetization, up to room temperature, is consistent with bulk measurements.

The (well) informed piano : internalization and growth process

The subject matter of this book is about piano methodology, including technical, musical, artistic, ethical and philosophical issues and reflections. The purpose of this work is to share a personal professional experience insight in the field of piano performance. This text assumes a certain continuity to the major contributions of artists like Ludwig Deppe, Tobias Matthay, Grigory Kogan, Heinrich Neuhaus and George Kochevitsky. At the same time, it tries to integrate and complement this selected literature, bringing new ideas and hints to specific professional issues.

Evaluation of the improvements on pharmacy technicians' work practices after implementation of operational procedures

Several antineoplasic drugs have been demonstrated to be carcinogenic or to have mutagenic and teratogenic effects. The greatest protection is achieved with the implementation of administrative and engineering controls and safety procedures. Objective: to evaluate the improvements on pharmacy technicians' work practices, after the implementation of operational procedures related to individual protection, biologic safety cabinet disinfection and cytotoxic drug preparation. Method: case-study in a hospital pharmacy undergoing a certification process. Six pharmacy technicians were observed during their daily activities. Characterization of the work practices was made using a checklist based on ISOPP and PIC guidelines. The variables studied concerning cleaning/disinfection procedures, personal protective equipment and procedures for preparing cytotoxic drugs. The same work practices were evaluated after four months of operational procedures implementation. Concordance between work practices and guidelines was considered to be a quality indicator (guidelines concordance practices number/total number of practices x 100). Results: improvements were observed after operational procedures implementation. An improvement of 6,25% in personal protective equipment practice was achieved by changing second pair of gloves every thirty minutes. The major progress, 10%, was obtained in disinfection procedure, where 80% of tasks are now realized according to guidelines.By now, we hot an improvement of only 1% at drug preparation procedure by placing one cytotoxic drug at a time inside the biological safety cabinet. Then, 85% of practices are according to guidelines. Conclusion: before operational procedures implementation 80,3% of practices were according to the guidelines, while now is 84,4%. This indicates that is necessary to review the procedures frequently in the benefit to reduce the risks associated with handling cytotoxic drugs and maintenance of drug specifications.

Work in progress: representar o «outro» segundo o pensamento antropofágico casos de estudo - Hans Staden e Les Maîtres Fous

O presente artigo analisa o filme de Luis Alberto Pereira «Hans Staden» (1999), baseado no livro de Hans Staden «Duas Viagens ao Brasil» (1557), e o documentário/filme «Les Maîtres Fous» (1955) de Jean Rouch, tendo em consideração o pensamento antropofágico. Estas obras focalizam o choque cultural entre “civilizado” e “selvagem”, entre ritual canibal e ritual antropofágico, entre o «Nós» e os «Outros», encontros que permitem uma análise mais concreta à concepção de alteridade. A representação cinematográfica permite uma aproximação ao conceito antropofágico de apropriação da cultura externa, para posteriormente a reproduzir numa interpretação segundo a concepção ocidental do que figuram os rituais em questão. O Movimento Antropófago, pelo seu carácter vanguardista, concilia a matriz fundadora brasileira e ao mesmo tempo enaltece a irreverência de análise, e neste artigo serve de fundamento teórico e prático à decomposição dos exemplos. O pensamento antropófago e a sua aplicabilidade aos exemplos seleccionados permitem também aprofundar o estudo sobre o imaginário europeu enquanto recriação de relatos datados de viajantes ou colonizadores, pois a manutenção de um acervo estereotipado historicamente serve como forma de “legitimar” concepções. As duas obras focalizam a representação indígena e africana - o “selvagem” - na construção do imaginário ocidental - “civilizado” - dicotomia que nos permite desmistificar relações interculturais.

Complex question answering on semi-structured repositories: a user centric process enhanced with context

A Teia Mundial (Web) foi prevista como uma rede de documentos de hipertexto interligados de forma a criar uma espaço de informação onde humanos e máquinas poderiam comunicar. No entanto, a informação contida na Web tradicional foi/é armazenada de forma não estruturada o que leva a que apenas os humanos a possam consumir convenientemente. Consequentemente, a procura de informações na Web sintáctica é uma tarefa principalmente executada pelos humanos e nesse sentido nem sempre é fácil de concretizar. Neste contexto, tornou-se essencial a evolução para uma Web mais estruturada e mais significativa onde é dado significado bem definido à informação de forma a permitir a cooperação entre humanos e máquinas. Esta Web é usualmente referida como Web Semântica. Além disso, a Web Semântica é totalmente alcançável apenas se os dados de diferentes fontes forem ligados criando assim um repositório de Dados Abertos Ligados (LOD). Com o aparecimento de uma nova Web de Dados (Abertos) Ligados (i.e. a Web Semântica), novas oportunidades e desafios surgiram. Pergunta Resposta (QA) sobre informação semântica é actualmente uma área de investigação activa que tenta tirar vantagens do uso das tecnologias ligadas à Web Semântica para melhorar a tarefa de responder a questões. O principal objectivo do projecto World Search passa por explorar a Web Semântica para criar mecanismos que suportem os utilizadores de domínios de aplicação específicos a responder a questões complexas com base em dados oriundos de diferentes repositórios. No entanto, a avaliação feita ao estado da arte permite concluir que as aplicações existentes não suportam os utilizadores na resposta a questões complexas. Nesse sentido, o trabalho desenvolvido neste documento foca-se em estudar/desenvolver metodologias/processos que permitam ajudar os utilizadores a encontrar respostas exactas/corretas para questões complexas que não podem ser respondidas fazendo uso dos sistemas tradicionais. Tal inclui: (i) Ultrapassar a dificuldade dos utilizadores visionarem o esquema subjacente aos repositórios de conhecimento; (ii) Fazer a ponte entre a linguagem natural expressa pelos utilizadores e a linguagem (formal) entendível pelos repositórios; (iii) Processar e retornar informações relevantes que respondem apropriadamente às questões dos utilizadores. Para esse efeito, são identificadas um conjunto de funcionalidades que são consideradas necessárias para suportar o utilizador na resposta a questões complexas. É também fornecida uma descrição formal dessas funcionalidades. A proposta é materializada num protótipo que implementa as funcionalidades previamente descritas. As experiências realizadas com o protótipo desenvolvido demonstram que os utilizadores efectivamente beneficiam das funcionalidades apresentadas: ▪ Pois estas permitem que os utilizadores naveguem eficientemente sobre os repositórios de informação; ▪ O fosso entre as conceptualizações dos diferentes intervenientes é minimizado; ▪ Os utilizadores conseguem responder a questões complexas que não conseguiam responder com os sistemas tradicionais. Em suma, este documento apresenta uma proposta que comprovadamente permite, de forma orientada pelo utilizador, responder a questões complexas em repositórios semiestruturados.

Economic, environmental and mixed objective functions in non-linear process optimization using simulated annealing and tabu search

Screening of topologies developed by hierarchical heuristic procedures can be carried out by comparing their optimal performance. In this work we will be exploiting mono-objective process optimization using two algorithms, simulated annealing and tabu search, and four different objective functions: two of the net present value type, one of them including environmental costs and two of the global potential impact type. The hydrodealkylation of toluene to produce benzene was used as case study, considering five topologies with different complexities mainly obtained by including or not liquid recycling and heat integration. The performance of the algorithms together with the objective functions was observed, analyzed and discussed from various perspectives: average deviation of results for each algorithm, capacity for producing high purity product, screening of topologies, objective functions robustness in screening of topologies, trade-offs between economic and environmental type objective functions and variability of optimum solutions.

Work in progress - learning through role play games

It is commonly accepted that the educational environment has been undergoing considerable change due to the use of the Information and Communication tools. But learning depends upon actions such as experimenting, visualizing and demonstrating through which the learner succeeds in constructing his own knowledge. Although it is not easy to achieve these actions through current ICT supported learning approaches, Role Playing Games (RPG) may well develop such capacities. The creation of an interactive computer game with RPG characteristics, about the 500th anniversary of the city of Funchal, the capital of Madeira Island, is invested with compelling educational/pedagogical implications, aiming clearly at teaching history and social relations through playing. Players interpret different characters in different settings/scenarios, experiencing adventures, meeting challenges and trying to reach multiple and simultaneous goals in the areas of education, entertainment and social integration along the first 150 years of the history of Funchal. Through this process they will live and understand all the social and historical factors of that epoch.