Functional characterisation of an engineered multidomain human P450 E1 by molecular Lego

The human cytochrome P450s constitute an important family of monooxygenase enzymes that carry out essential roles in the metabolism of endogenous compounds and foreign chemicals. We present here results of a fusion between a human P450 enzyme and a bacterial reductase that for the first time is shown does not require the addition of lipids or detergents to achieve wild-type-like activities. The fusion enzyme, P450 2E1-BMR, contains the N-terminally modified residues 22-493 of the human P450 2E1 fused at the C-terminus to residues 473-1049 of the P450 BM3 reductase (BMR). The P450 2E1-BMR enzyme is active, self-sufficient and presents the typical marker activities of the native human P450 2E1: the hydroxylation of p-nitrophenol (K (M)=1.84 +/- 0.09 mM and k (cat) of 2.98 +/- 0.04 nmol of p-nitrocatechol formed per minute per nanomole of P450) and chlorzoxazone (K (M)=0.65 +/- 0.08 mM and k (cat) of 0.95 +/- 0.10 nmol of 6-hydroxychlorzoxazone formed per minute per nanomole of P450). A 3D model of human P450 2E1 was generated to rationalise the functional data and to allow an analysis of the surface potentials. The distribution of charges on the model of P450 2E1 compared with that of the FMN domain of BMR provides the ground for the understanding of the interaction between the fused domains. The results point the way to successfully engineer a variety of catalytically self-sufficient human P450 enzymes for drug metabolism studies in solution.

Trade marks, registered designs and the monopolisation of functional shapes:a consideration of Lego and Dyson

Legislation: Regulation 6/2002 on Community designs art.3(3)(e) Directive 98/71 on the legal protection of designs art.7(1) Cases: Dyson Ltd v Vax Ltd [2010] EWHC 1923 (Pat); [2011] Bus. L.R. 232 (Ch D (Patents Ct)) Lego Juris A/S v Office for Harmonisation in the Internal Market (Trade Marks and Designs) (OHIM) (C-48/09 P) Unreported September 14, 2010 (ECJ) *E.I.P.R. 60 In Lego, the Court of Justice of the European Union denied registration for an exclusively functional shape mark despite the availability of other shapes capable of fulfilling the same function and in Dyson v Vax Mr Justice Arnold established that a design can not be registered for a purely functional shape even though another shape could fulfil the same required function.

Der Einfluss von Lego Mindstorms Experimenten auf das Interesse von Lernenden und deren Vorstellung zum Energiebegriff

Studien zufolge ist das Schulfach Physik eines der unbeliebtesten Schulfächer. Die Beweggründe für diese Einstellungen sind vielfältig: Kaum ein Schulfach verwendet eine so künstliche Sprache und begibt sich in eine derart abstrakte und nüchterne Gedanken- und Zahlenwelt. Um die Defizite des Physikunterrichts zu überwinden, gab es in den vergangenen Jahren immer wieder Versuche von Lehrmittelherstellern, aktuelle Forschungsergebnisse der Physik-Fachdidaktik in die Entwicklung von Lehrmitteln für den Physikunterricht einfließen zu lassen. Auch der dänische Spielzeughersteller Lego bietet seit 1998 mit seinem Lego Mindstorms System ein Lehrmittel an, das neben dem Einsatz im Informatik- und Mathematikunterricht auch Möglichkeiten zur Anwendung im Physikunterricht zulässt. Die aktuellste Version der Lego Mindstorms bietet zahlreiche Versuche zu verschiedenen Bereichen der Physik an. Lego Mindstorms Experimente ermöglichen so einen spielerischen und positiv belegten Zugang zu Physikexperimenten. Allerdings stellt sich die Frage, inwiefern die Lego Mindstorms Experimente geeignet sind, die eingangs benannten Defizite des Physikunterrichts zu verringern. Kann der Einsatz von Lego Mindstorms Physikexperimenten also dazu beitragen, Lernbarrieren und Hemmnisse abzubauen, das Selbstkonzept der Lernenden sowie deren Interesse am Physikunterricht zu verbessern und gleichzeitig einen kontextorientierten und fachwissenschaftlich fundierten Unterricht zu ermöglichen?

AITPM Email Newsletter Volume 0910, October 2009 : Presidents Message

President’s Message Hello fellow AITPM members, Well I can’t believe it’s already October! My office is already organising its end of year function and looking to plan for 2010. Our whole School is moving to a different building next year, with the lovely L block eventually making way for a new shiny one. Those of you who have entered the Brisbane CBD from the south side, across the Captain Cook Bridge, would know L block as the big 9 storey brick and concrete Lego block ode to 1970’s functional architecture, which greets you on the right hand side. Onto traffic matters: an issue that has been tossing around in my mind of late is that of speed. I know I am growing older and may be prematurely becoming a “grumpy old man”, but everyone around me locally seems to be accelerating off from the stop line much faster than I was taught to for economical driving, both here and in the United States (yes they made my wife and me resit our written and practical driving tests when we lived there). People here in Australia also seem to be driving right on top of the posted speed limit, on whichever part of the Road Hierarchy, whether urban or rural. I was also taught on both sides of the planet that the posted speed limit is a maximum legal speed, not the recommended driving speed. This message did seem to sink in to the American drivers around me when we lived in Oregon - where people did appear to drive more cautiously. Further, posted speed limits in Oregon were, and I presume still are, set more conservative by about 5mph or 10km/h than Australian limits, for any given part of the Road Hierarchy. Another excellent speed limit treatment used in Oregon was in school zones, where reduced speed limits applied “when children are present” rather than during prescribed hours on school days. This would be especially useful here in Australia, where a lot of extra-curricular activities take place around schools outside of the prescribed speed limit hours. Before and after hours school care is on the increase (with parents dropping and collecting children near dawn and dusk in the winter), and many childcentred land uses are located adjacent to schools, such as Scouts/Guides halls, swimming pools and parks. Consequentially, I believe there needs to be some consideration towards more public campaigning about economical driving and the real purpose of the speed limit = or perhaps even a rethink of the speed limit concept, if people really are driving on top of it and it’s not just me becoming grumpier (our industrial psychology friends at the research centres may be able to assist us here). The Queensland organising committee is now in full swing organising the 2010 AITPM National Conference, What’s New?, so please keep a lookout for related content. Best regards to all, Jon Bunker PS A Cartoonists view of traffic engineers I thought you might enjoy this. http://xkcd.com/277/

Problem solving in a middle school robotics design classroom

Little research has been conducted on how students work when they are required to plan, build and evaluate artefacts in technology rich learning environments such as those supported by tools including flow charts, Labview programming and Lego construction. In this study, activity theory was used as an analytic tool to examine the social construction of meaning. There was a focus on the effect of teachers’ goals and the rules they enacted upon student use of the flow chart planning tool, and the tools of the programming language Labview and Lego construction. It was found that the articulation of a teacher’s goals via rules and divisions of labour helped to form distinct communities of learning and influenced the development of different problem solving strategies. The use of the planning tool flow charting was associated with continuity of approach, integration of problem solutions including appreciation of the nexus between construction and programming, and greater educational transformation. Students who flow charted defined problems in a more holistic way and demonstrated more methodical, insightful and integrated approaches to their use of tools. The findings have implications for teaching in design dominated learning environments.

Preparing general technology teachers in China for new roles and responsibilities

This paper discusses the conceptualization, implementation and initial findings of a professional learning program (PLP) which used LEGO® robotics as one of the tools for teaching general technology (GT)in China’s secondary schools. The program encouraged teachers to design learning environments that can be realistic, authentic, engaging and fun. 100 general technology teachers from high schools in 30 provinces of China participated. The program aimed to transform teacher classroom practice, change their beliefs and attitudes, allow teachers to reflect deeply on what they do and in turn to provide their students with meaningful learning. Preliminary findings indicate that these teachers had a huge capacity for change. They were open-minded and absorbed new ways of learning and teaching. They became designers who developed innovative models of learning which incorporated learning processes that effectively used LEGO® robotics as one of the more creative tools for teaching GT.

Less but more : weaving disparate disciplines together for learners to construct their own knowledge

This paper reports on a Professional Learning Program conducted in China with 140 general technology teachers. It aimed to integrate robotics technology across and within the disciplines of science, technology, engineering and mathematics. With the help of university facilitators teachers developed General Technology lessons that seamlessly integrated with rich learning content across disciplines. Teachers engaged in seminars and workshops, which provided the opportunities for them to actively couch sound principles of learning in their daily work. They gained first-hand experience in applying an aligned system of assessments, standards and quality learning experiences geared to the needs of each student. Teachers worked collaboratively in teams to create inquiry, design and collaborative learning activities that aligned with their curriculum and which dealt with real world problems, issues and challenges. They continually discussed and reflected deeply on the activities and shared the newly developed resources online with teachers across the entire country. It is evident from the preliminary analysis of data that teachers are beginning to apply rich pedagogical practices and are becoming ‘adaptive’ in their approach when using LEGO® robotic tools to design, redesign, create and re-create learning activities for their students.

Visual route recognition with a handful of bits

In this paper we use a sequence-based visual localization algorithm to reveal surprising answers to the question, how much visual information is actually needed to conduct effective navigation? The algorithm actively searches for the best local image matches within a sliding window of short route segments or 'sub-routes', and matches sub-routes by searching for coherent sequences of local image matches. In contract to many existing techniques, the technique requires no pre-training or camera parameter calibration. We compare the algorithm's performance to the state-of-the-art FAB-MAP 2.0 algorithm on a 70 km benchmark dataset. Performance matches or exceeds the state of the art feature-based localization technique using images as small as 4 pixels, fields of view reduced by a factor of 250, and pixel bit depths reduced to 2 bits. We present further results demonstrating the system localizing in an office environment with near 100% precision using two 7 bit Lego light sensors, as well as using 16 and 32 pixel images from a motorbike race and a mountain rally car stage. By demonstrating how little image information is required to achieve localization along a route, we hope to stimulate future 'low fidelity' approaches to visual navigation that complement probabilistic feature-based techniques.

Introducing ICT to a primary school in a developing country : a Fijian experience

One aspect of quality education in the 21st century is the availability of digital resources in schools. Many developing countries need to build this capability – not just in terms of technology but teacher capability as well. One of the ways to achieve such capacity is through knowledge sharing between teachers and educators in developed and developing countries. Over time such collaboration can have a lasting impact on all participants on both sides of the digital divide. This paper reports on how such collaboration can occur. It focuses on the initial stages of a long-term initiative where our primary objective is to develop models, which demonstrate how we (in developed countries) can engage productively and meaningfully with schools in developing countries to build their ICT capacity. As part of this initiative, we introduced laptops and LEGO robotics tool kits to a rural primary school in Fiji. We developed ICT activities that aligned with the curriculum in a number of subjects. In addition, we worked with the teachers over two weeks to build their expertise.

The architecture of children’s use of language and tools when problem solving collaboratively with robotics

This paper demonstrates, following Vygotsky, that language and tool use has a critical role in the collaborative problem-solving behaviour of school-age children. It reports original ethnographic classroom research examining the convergence of speech and practical activity in children’s collaborative problem solving with robotics programming tasks. The researchers analysed children’s interactions during a series of problem solving experiments in which Lego Mindstorms toolsets were used by teachers to create robotics design challenges among 24 students in a Year 4 Australian classroom (students aged 8.5–9.5 years). The design challenges were incrementally difficult, beginning with basic programming of straight line movement, and progressing to more complex challenges involving programming of the robots to raise Lego figures from conduit pipes using robots as pulleys with string and recycled materials. Data collection involved micro-genetic analysis of students’ speech interactions with tools, peers, and other experts, teacher interviews, and student focus group data. Coding the repeated patterns in the transcripts, the authors outline the structure of the children’s social speech in joint problem solving, demonstrating the patterns of speech and interaction that play an important role in the socialisation of the school-age child’s practical intellect.

Interacción corporal con el ordenador para niños con restricciones motoras

Para los niños el juego es la manera más natural de aprender. Mediante el juego los niños interactúan con su entorno. Cuando se trata de niños con graves restricciones motoras esta interacción se ve limitada. Es por esta razón por la que intentamos poner los medios existentes a su disposición. Este proyecto muestra una interfaz persona-computador para manejar un robot Lego Mindstorm RCX en un entorno virtual proyectado sobre una superficie. En todo momento el sistema es capaz de determinar la posición del robot mediante un sensor Microsoft Kinect. Pretende ser el primer paso en la creación de una interfaz persona-computador para niños con restricciones motoras que ayude en su rehabilitación.

Programación de un robot planar para que dibuje

Duración (en horas): De 41 a 50 horas. Destinatario: Estudiante y Docente

Sistemas inteligentes adaptativos aplicados a um robô auto-equilibrante de duas rodas.

Com o avanço no desenvolvimento e utilização de veículos e robôs autoequilibrantes, faz-se necessário a investigação de controladores capazes de atender os diversos desafios relacionados à utilização desses sistemas. Neste trabalho foi estudado o controle de equilíbrio e posição de um robô auto-equilibrante de duas rodas. O interesse particular nesta aplicação vem da sua estrutura e da riqueza de sua dinâmica física. Por ser um problema complexo e não trivial há grande interesse em avaliar os controladores inteligentes. A primeira parte da dissertação aborda o desenvolvimento de um controle clássico do tipo PID, para em seguida ser comparado com a implementação de dois tipos de controladores inteligentes: On-line Neuro Fuzzy Control (ONFC) e Proportional-Integral-Derivative Neural-Network (PIDNN). Também é apresentada a implementação dos controladores em uma plataforma de hardware, utilizando o kit LEGO Mindstorm, e numa plataforma de simulação utilizando o MATLAB-Simulink. Em seguida, dois estudos de casos são desenvolvidos visando comparar o desempenho dos controladores. O primeiro caso avalia o controle de equilíbrio e posição do robô auto-equilibrante de duas rodas sobre um terreno plano tendo como interesse observar o desempenho intrínseco do sistema sob ausência de fatores externos. O segundo caso estuda o controle de equilíbrio e posição do robô em terrenos irregulares visando investigar a resposta do sistema sob influência de condições adversas em seu ambiente. Finalmente, o desempenho de cada um dos controladores desenvolvidos é discutido, verificando-se resultados competitivos no controle do robô auto-equilibrante de duas rodas.

Do persistent organic pollutants interact with the stress response? Individual compounds, and their mixtures, interaction with the glucocorticoid receptor

Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential (UNEP 2001). The majority of studies on endocrine disruption have focused on interferences on the sexual steroid hormones and so have overlooked disruption to glucocorticoid hormones. Here the endocrine disrupting potential of individual POPs and their mixtures has been investigated in vitro to identify any disruption to glucocorticoid nuclear receptor transcriptional activity. POP mixtures were screened for glucocorticoid receptor (GR) translocation using a GR redistribution assay (RA) on a CellInsight(TM) NXT High Content Screening (HCS) platform. A mammalian reporter gene assay (RGA) was then used to assess the individual POPs, and their mixtures, for effects on glucocorticoid nuclear receptor transactivation. POP mixtures did not induce GR translocation in the GR RA or produce an agonist response in the GR RGA. However, in the antagonist test, in the presence of cortisol, an individual POP, p,p'-dichlorodiphenyldichloroethylene (DDE), was found to decrease glucocorticoid nuclear receptor transcriptional activity to 72.5% (in comparison to the positive cortisol control). Enhanced nuclear transcriptional activity, in the presence of cortisol, was evident for the two lowest concentrations of perfluorodecanoic acid (PFOS) potassium salt (0.0147mg/ml and 0.0294mg/ml), the two highest concentrations of perfluorodecanoic acid (PFDA) (0.0025mg/ml and 0.005mg/ml) and the highest concentration of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) (0.0000858mg/ml). It is important to gain a better understanding of how POPs can interact with GRs as the disruption of glucocorticoid action is thought to contribute to complex diseases.