Pharmacokinetic software for the health sciences - Choosing the right package for teaching purposes

Computer assisted learning has an important role in the teaching of pharmacokinetics to health sciences students because it transfers the emphasis from the purely mathematical domain to an 'experiential' domain in which graphical and symbolic representations of actions and their consequences form the major focus for learning. Basic pharmacokinetic concepts can be taught by experimenting with the interplay between dose and dosage interval with drug absorption (e.g. absorption rate, bioavailability), drug distribution (e.g. volume of distribution, protein binding) and drug elimination (e.g. clearance) on drug concentrations using library ('canned') pharmacokinetic models. Such 'what if' approaches are found in calculator-simulators such as PharmaCalc, Practical Pharmacokinetics and PK Solutions. Others such as SAAM II, ModelMaker, and Stella represent the 'systems dynamics' genre, which requires the user to conceptualise a problem and formulate the model on-screen using symbols, icons, and directional arrows. The choice of software should be determined by the aims of the subject/course, the experience and background of the students in pharmacokinetics, and institutional factors including price and networking capabilities of the package(s). Enhanced learning may result if the computer teaching of pharmacokinetics is supported by tutorials, especially where the techniques are applied to solving problems in which the link with healthcare practices is clearly established.

Pyramidal neurones in macaque visual cortex: Interareal phenotypic variation of dendritic branching patterns

The basal dendritic arbors of over 500-layer III pyramidal neurones of the macaque cortex were compared by fractal analyses, which provides a measure of the space filling (or branching pattern) of dendritic arbors. Fractal values (D) of individual cells were compared between the cytochrome oxidase (CO)-rich blobs and CO-poor interblobs, of middle and upper layer III, and between sublaminae, in the primary visual area (Vi). These data were compared with those in the CO compartments in the second visual area (V2), and seven other extrastriate cortical areas. (V4, MT, LIP, 7a, TEO, TE and STP). There were significant differences in the fractal dimensions, and therefore the dendritic branching patterns, of cells in striate and extrastriate areas. Of the 55 possible pairwise comparisons of fractal dimension of neurones in different cortical areas (or CO compartments), 39 proved to be significantly different. The markedly different morphologies of pyramidal cells in the different cortical areas may be one of the features that determine the functional signatures of these cells by influencing the number of inputs received by, and propagation of potentials through, their dendritic arbors.

A multifunctional polyketide-peptide synthetase essential for albicidin biosynthesis in Xanthomonas albilineans

Albicidins, a family of potent antibiotics and phytotoxins produced by the sugarcane leaf scald pathogen Xanthomonas albilineans, inhibit DNA replication in bacteria and plastids. A gene located by Tn5-tagging was confirmed by complementation to participate in albicidin biosynthesis. The gene (xabB) encodes a large protein (predicted Mr 525695), with a modular architecture indicative of a multifunctional polyketide synthase (PKS) linked to a non-ribosomal peptide synthetase (NRPS). At 4801 amino acids in length, XabB is the largest reported PKS–NRPS. Twelve catalytic domains in this multifunctional enzyme are arranged in the order N terminus–acyl-CoA ligase (AL)–acyl carrier protein (ACP)–ß-ketoacyl synthase (KS)–ß-ketoacyl reductase (KR)–ACP–ACP–KS–peptidyl carrier protein (PCP)–condensation (C)–adenylation–PCP–C. The modular architecture of XabB indicates likely steps in albicidin biosynthesis and approaches to enhance antibiotic yield. The novel pattern of domains, in comparison with known PKS–NRPS enzymes for antibiotic production, also contributes to the knowledge base for rational design of enzymes producing novel antibiotics.

Development of a generic crop model template in the cropping system model APSIM

The Agricultural Production Systems slMulator, APSIM, is a cropping system modelling environment that simulates the dynamics of soil-plant-management interactions within a single crop or a cropping system. Adaptation of previously developed crop models has resulted in multiple crop modules in APSIM, which have low scientific transparency and code efficiency. A generic crop model template (GCROP) has been developed to capture unifying physiological principles across crops (plant types) and to provide modular and efficient code for crop modelling. It comprises a standard crop interface to the APSIM engine, a generic crop model structure, a crop process library, and well-structured crop parameter files. The process library contains the major science underpinning the crop models and incorporates generic routines based on physiological principles for growth and development processes that are common across crops. It allows APSIM to simulate different crops using the same set of computer code. The generic model structure and parameter files provide an easy way to test, modify, exchange and compare modelling approaches at process level without necessitating changes in the code. The standard interface generalises the model inputs and outputs, and utilises a standard protocol to communicate with other APSIM modules through the APSIM engine. The crop template serves as a convenient means to test new insights and compare approaches to component modelling, while maintaining a focus on predictive capability. This paper describes and discusses the scientific basis, the design, implementation and future development of the crop template in APSIM. On this basis, we argue that the combination of good software engineering with sound crop science can enhance the rate of advance in crop modelling. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Simulation of the micro-physics of rocks using LSMearth

The particle-based Lattice Solid Model (LSM) was developed to provide a basis to study the physics of rocks and the nonlinear dynamics of earthquakes (MORA and PLACE, 1994; PLACE and MORA, 1999). A new modular and flexible LSM approach has been developed that allows different microphysics to be easily included in or removed from the model. The approach provides a virtual laboratory where numerical experiments can easily be set up and all measurable quantities visualised. The proposed approach provides a means to simulate complex phenomena such as fracturing or localisation processes, and enables the effect of different micro-physics on macroscopic behaviour to be studied. The initial 2-D model is extended to allow three-dimensional simulations to be performed and particles of different sizes to be specified. Numerical bi-axial compression experiments under different confining pressure are used to calibrate the model. By tuning the different microscopic parameters (such as coefficient of friction, microscopic strength and distribution of grain sizes), the macroscopic strength of the material and can be adjusted to be in agreement with laboratory experiments, and the orientation of fractures is consistent with the theoretical value predicted based on Mohr-Coulomb diagram. Simulations indicate that 3-D numerical models have different macroscopic properties than in 2-D and, hence, the model must be recalibrated for 3-D simulations. These numerical experiments illustrate that the new approach is capable of simulating typical rock fracture behaviour. The new model provides a basis to investigate nucleation, rupture and slip pulse propagation in complex fault zones without the previous model limitations of a regular low-level surface geometry and being restricted to two-dimensions.

An overview of APSIM, a model designed for farming systems simulation

The Agricultural Production Systems Simulator (APSIM) is a modular modelling framework that has been developed by the Agricultural Production Systems Research Unit in Australia. APSIM was developed to simulate biophysical process in farming systems, in particular where there is interest in the economic and ecological outcomes of management practice in the face of climatic risk. The paper outlines APSIM's structure and provides details of the concepts behind the different plant, soil and management modules. These modules include a diverse range of crops, pastures and trees, soil processes including water balance, N and P transformations, soil pH, erosion and a full range of management controls. Reports of APSIM testing in a diverse range of systems and environments are summarised. An example of model performance in a long-term cropping systems trial is provided. APSIM has been used in a broad range of applications, including support for on-farm decision making, farming systems design for production or resource management objectives, assessment of the value of seasonal climate forecasting, analysis of supply chain issues in agribusiness activities, development of waste management guidelines, risk assessment for government policy making and as a guide to research and education activity. An extensive citation list for these model testing and application studies is provided. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Direct visualization of Ras proteins in spatially distinct cell surface microdomains

Localization of signaling complexes to specific micro-domains coordinates signal transduction at the plasma membrane. Using immunogold electron microscopy of plasma membrane sheets coupled with spatial point pattern analysis, we have visualized morphologically featureless microdomains including lipid rafts, in situ and at high resolution. We find that an inner-plasma membrane lipid raft marker displays cholesterol-dependent clustering in microdomains with a mean diameter of 44 nm that occupy 35% of the cell surface. Cross-linking an outer-leaflet raft protein results in the redistribution of inner leaflet rafts, but they retain their modular structure. Analysis of Ras microlocalization shows that inactive H-ras is distributed between lipid rafts and a cholesterol-independent micro-domain. Conversely, activated H-ras and K-ras reside predominantly in nonoverlapping, cholesterol-independent microdomains. Galectin-1 stabilizes the association of activated H-ras with these nonraft microdomains, whereas K-ras clustering is supported by farnesylation, but not geranylgeranylation. These results illustrate that the inner plasma membrane comprises a complex mosaic of discrete microdomains. Differential spatial localization within this framework can likely account for the distinct signal outputs from the highly homologous Ras proteins.

Digitally-implemented naturally sampled PWM suitable for multilevel converter control

For dynamic closed loop control of a multilevel converter with a low pulse number (ratio of switching frequency to synthesized fundamental), natural sampled pulse-width modulation (PWM) is the best form of modulation. Natural sampling does not introduce distortion or a delayed response to the modulating signal. However previous natural sampled PWM implementations have generally been analog. For a modular multilevel converter, a digital implementation has advantages of accuracy and flexibility. Re-sampled uniform PWM is a novel digital modulation technique which approaches the performance of natural PWM. Both hardware and software implementations for a five level multilevel converter phase are presented, demonstrating the improvement over uniform PWM.

Efeito da mitomicina C tópica na cicatrização de prega vocal em modelo suíno

Várias terapias adjuvantes à cirurgia vêm sendo usadas para modular o processo cicatricial nas pregas vocais, entre elas a Mitomicina tópica (MTC). OBJETIVOS: Avaliar os efeitos da MTC no processo de cicatrização de pregas vocais de suínos 30 dias após exérese de fragmento de mucosa com laser de CO2 mediante a mensuração da deposição de colágeno. FORMA DE ESTUDO: Experimental em suínos. MATERIAIS E MÉTODOS: Dois grupos de 6 suínos cada foram avaliados após exérese de fragmento de mucosa de prega vocal a laser de CO2 (grupo controle sem uso e grupo experimento com uso de MTC tópica). Após 30 dias os animais foram submetidos à eutanásia, sendo coletadas amostras das pregas vocais para análise histológica, a fim de quantificar a deposição de colágeno mediante coloração de Picrosirius Red. RESULTADOS: A média da área do colágeno total das pregas vocais do grupo controle foi de 2648,03 µm2, enquanto a média do colágeno total das pregas vocais do grupo experimento foi de 2200,30 µm2 (p = 0,0043). CONCLUSÃO: A MTC usada topicamente após a exérese de fragmento de mucosa da prega vocal a laser de CO2 em suínos, diminui, significativamente, a deposição do colágeno total.

REENGINEERING THE CONCEPT OF URBAN CARS: A CASE STUDY

Based on a previously developed mathematical model for fuel consumption of a modular car, here we discuss the cross impacts of engineering scenarios vs. flexibility in use for modular vehicle architectures to achieve the reduction of CO2 emissions targeted by the European Union, in 2009. A systems perspective is adopted in conceptualizing a modular architecture of vehicles. From a theoretical viewpoint, we found modular architecture of vehicles a potential design strategy to minimize fuel inefficiencies and, thus, a strategy for design for environment.

A laparoscopic surgery training interface

Laparoscopy is a surgical procedure on which operations in the abdomen are performed through small incisions using several specialized instruments. The laparoscopic surgery success greatly depends on surgeon skills and training. To achieve these technical high-standards, different apprenticeship methods have been developed, many based on in vivo training, an approach that involves high costs and complex setup procedures. This paper explores Virtual Reality (VR) simulation as an alternative for novice surgeons training. Even though several simulators are available on the market claiming successful training experiences, their use is extremely limited due to the economic costs involved. In this work, we present a low-cost laparoscopy simulator able to monitor and assist the trainee’s surgical movements. The developed prototype consists of a set of inexpensive sensors, namely an accelerometer, a gyroscope, a magnetometer and a flex sensor, attached to specific laparoscopic instruments. Our approach allows repeated assisted training of an exercise, without time constraints or additional costs, since no human artificial model is needed. A case study of our simulator applied to instrument manipulation practice (hand-eye coordination) is also presented.

Produto Aquaoli: projeto de design industrial em aquariofilia

Esta dissertação de mestrado, apresenta a elaboração de um projeto de design industrial em aquariofilia - Aquaoli. Pretende-se criar uma nova tipologia de aquários inovadora e distinta, projetando o produto com o intuito deste cumprir com todos os parâmetros exigidos pelo mercado e produção do mesmo. Definiu-se a criança entre os 7 e os 11 anos como público-alvo deste projeto. Assim, pretende-se um resultando promissor para a empresa AQUATLANTIS apostar e lucrar com o seu desenvolvimento. Para que este projeto obtivesse bons resultados, foi realizada uma pesquisa aprofundada, desde a aquariofilia (a sua história, biologia e mercado), do aquariófilo atual (psicologia do consumidor e as suas responsabilidades), até ao estado da arte (da AQUATLANTIS e dos produtos existentes no mercado). Este projeto foi desenvolvido em várias vertentes de design, procurando ser o mais completo possível. Isso foi viável com o desenvolvimento do produto e de todos os seus componentes em três dimensões, o desenvolvimento de maquetes e de protótipos do produto, o desenvolvimento do packaging e campanha promocional, a definição de preço custo e métodos de produção dos objetos, entre outros parâmetros. Obteve-se um projeto de design industrial bastante completo e com potencial para ser implementado no mercado, cativando a atenção do público-alvo e obtendo vendas elevadas. O aquário apresenta-se distinto dos existentes, principalmente no facto de ser modular, muito interativo, pedagógico e incorporar uma estrutura invulgar e particularmente cativante para as crianças. Este produto subdivide-se em dois conjuntos vendidos separadamente (Aquarium Pack e Kit-1 Pack), apresentando assim uma estratégia de marketing que pretende que a criança que o adquira pela primeira vez, venha a desejar adquirir mais produtos desta gama, procurando aumentar a sua estante e/ou o número de aquários e animais que incorpora na mesma.

Cristalização de Biomateriais Vitrocerâmicos e Mineralização em Meio Fisiológico Simulado

We propose new theoretical models, which generalize the classical Avrami-Nakamura models. These models are suitable to describe the kinetics of nucleation and growth in transient regime, and/or with overlapping of nucleation and growth. Simulations and predictions were performed for lithium disilicate based on data reported in the literature. One re-examined the limitations of the models currently used to interpret DTA or DSC results, and to extract the relevant kinetic parameters. Glasses and glass-ceramics with molar formulation 0.45SiO2? (0.45-x)MgO?xK2O?0.1(3CaO.P2O5) (0?x?0.090) were prepared, crystallized and studied as potential materials for biomedical applications. Substitution of K+ for Mg2+ were used to prevent devritification on cooling, to adjust the kinetics of crystallization and to modify the in vitro behaviour of resulting biomaterials. The crystallization of the glass frits was studied by DTA, XRD and SEM. Exothermic peaks were detected corresponding to bulk crystallization of whitlockite-type phosphate, Ca9MgK(PO4)7, at approximately 900ºC, and surface crystallization of a predominant forsterite phase (Mg2SiO4) at higher temperatures. XRD also revealed the presence of diopside (CaMgSi2O6 in some samples. The predominant microstructure of the phosphate phase is of the plate-type, seemingly crystallizing by a 2-dimensional growth mechanism. Impedance spectroscopy revealed significant changes in electrical behaviour, associated to crystallization of the phosphate phase. This showed that electrical measurements can be used to study the kinetics of crystallization for cases when DTA or DSC experiments reveal limitations, and to extract estimates of relevant parameters from the dependence of crystallization peak temperature, and its width at half height. In vitro studies of glasses and glass-ceramics in acelular SBF media showed bioactivity and the development of apatite layers The morphology, composition and adhesion of the apatite layer could be changed by substitution of Mg2+ by K+. Apatite layers were deposited on the surface of glass-ceramics of the nominal compositions with x=0 and 0.09, in contact with SBF at 37ºC. The adhesion of the apatite layer was quantified by the scratch test technique, having been related with SBF?s immersion time, with composition and structure of the glass phase, and with the morphology of the crystalline phase of the glass-ceramics. The structure of three glasses (x=0, 0.045 and 0.090) were investigated by MAS-NMR ( 29Si and 31P), showing that the fraction of Q3 structural units increases with the contents of Mg, and that the structure of these glasses includes orthophosphate groups (PO43-) preferentially connected to Ca2+ ions. Mg2+ ions show preference towards the silicate network. Substitution of Mg2+ by K+ allowed one to change the bioactivity. FTIR data revealed octacalcium phosphate precipitation (Ca8H2(PO4)6.5H2O) in the glass without K, while the morphology of the layer acquires the shape of partially superimposed hemispheres, spread over the surface. The glasses with K present a layer of acicular hidroxyapatite, whose crystallinity and needles thickness tend to increase along with K content.

Integração de informação geográfica

A integração de informação geográfica disponível em diferentes formatos levanta a necessidade de criar mecanismos de resolução de incompatibilidades, tendo em vista facilitar a partilha e reutilização de informação. No âmbito desta dissertação, propõe-se uma arquitectura que efectue a integração de informação geográfica. A arquitectura processa diferentes fontes de informação geográfica com diferentes formatos. A informação geográfica apresentada nas entradas é transformada atendendo a um formato de representação interno e, após ser realizada a sua integração, é disponibilizada em múltiplos formatos de saída. A arquitectura proposta é modular e inclui o módulo de leitura das entradas, o módulo que associa as fontes de informação aos respectivos formatos, o módulo de conversão dos dados de entrada no formato de representação interno e o módulo de integração que gera os dados nos diferentes formatos de saída. Com o objectivo de avaliar experimentalmente a arquitectura, foi desenvolvido um protótipo. Foram processados exemplos de informação geográfica relativos a cenários de integração que cobrem as funcionalidades da arquitectura, nomeadamente a inclusão de novos formatos de informação geográfica e a integração de fontes de informação homogéneas ou heterogéneas. Os resultados obtidos confirmam que a arquitectura proposta é adequada à integração de fontes de informação geográfica e que é uma contribuição válida para a resolução de problemas de interoperabilidade em sistemas de informação geográfica.

Consumo energético e eficiência da marcha com dois modelos de joelhos protésicos: estudo de caso

Introdução – Os componentes protésicos têm um papel fundamental na eficiência energética da marcha dos indivíduos amputados. Esta é uma área de conhecimento ainda em desenvolvimento, onde a investigação desempenha um papel central. Objectivos – Comparar e analisar o efeito de dois joelhos protésicos, 3R34, monocêntrico modular, de fricção constante, com auxiliar de extensão incorporado (A) e 3R92, monocêntrico modular, com travão de fricção e controlo pneumático da fase de balanço (B) no consumo energético e eficiência da marcha. Metodologia – Um indivíduo do sexo masculino de 27 anos, com amputação transfemural longa, foi sujeito a um protocolo submáximo de avaliação da resposta ao exercício em passadeira rolante (H/P/Cosmos(R) Mercury), através de um sistema de análise de gases breath‑by‑breath (Cosmed Quark PFT Ergo). Foi efetuado o mesmo protocolo com intervalo de dois dias, primeiro utilizando o joelho A e depois o B. As variáveis analisadas foram o consumo de O2 (VO2), o equivalente metabólico (MET) e a eficiência energética da marcha (Quociente de VO2 esperado de um individuo saudável e o VO2 do individuo em estudo). O esforço percecionado foi medido com a escala RPE de Borg. Resultados – O consumo energético com o joelho A (24,2 ml O2/kg/min; 6,9 MET) foi inferior ao obtido com o joelho B (28,68 ml O2/kg/min; 8,2 MET). A eficiência energética da marcha foi mais elevada para o joelho A (43%) do que para o joelho B (39%). Conclusão – A utilização do joelho A na prótese do indivíduo em estudo resulta numa marcha de menor consumo energético e maior eficiência. No entanto, este valor poderá estar influenciado pelo curto período de adaptação ao joelho B, sendo necessários mais estudos para confirmar os resultados do estudo e a influência deste fator. ABSTRACT - Background – Prosthetic components have a crucial role in the energy efficiency of amputee’s gait. This is an area of knowledge still in development, where research plays a central role. Objective – The purpose of this case study is to compare the impact in energy consumption of two prosthetic knees, titanium single‑axis constant friction knee joint with internal extension assist, 3R34 (A) and a single‑axis pneumatic swing phase control, 3R92 (B). Methodology – The participant was a transtibial amputee, male, with 27 years old, with no other clinical or functional impairments. To measure the energy expenditure a submaximal treadmill (H/P/Cosmos(R) Mercury) exercise stress test combined with a breath‑by‑breath analysis system (Cosmed Quark PFT Ergo) was used. The same test was applied to both knees, separated by two days. The analyzed variables were O2 consumption (VO2), metabolic equivalent (MET) and gait efficiency (VO2 ratio expected from a healthy individual and the studied individual). A rate of perceived exertion (Borg’s Scale) was used. Results – The results were favorable to knee A (24.2 ml O2/kg/min; 6.9 MET, 43% efficiency) compared with knee B (28.68 ml O2/kg/min; 8.2 MET, 39% efficiency). Conclusion – In this case, a less energy consumption gait corresponds to the prosthesis with knee A. These values may be influenced by the short adaptation period with knee B, so it’s necessary to perform more studies to confirm the previous results and to understand the truly impact of correct adaptation factor to the best prosthetics components for different patients.