Efficient and accurate experimental design for enzyme kinetics: Bayesian studies reveal a systematic approach

In areas such as drug development, clinical diagnosis and biotechnology research, acquiring details about the kinetic parameters of enzymes is crucial. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. We demonstrate that a Bayesian approach (the use of prior knowledge) can produce major gains quantifiable in terms of information, productivity and accuracy of each experiment. Developing the use of Bayesian Utility functions, we have used a systematic method to identify the optimum experimental designs for a number of kinetic model data sets. This has enabled the identification of trends between kinetic model types, sets of design rules and the key conclusion that such designs should be based on some prior knowledge of K-M and/or the kinetic model. We suggest an optimal and iterative method for selecting features of the design such as the substrate range, number of measurements and choice of intermediate points. The final design collects data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. (C) 2003 Elsevier Science B.V. All rights reserved.

The design of probiotic studies to substantiate health claims

The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials.

Studies of Design and Assembly Defects on Integrated and Modular Architectures

It is known that despite companies’ efforts to improve the quality of their products, design and assembly defects results in large repair costs both in terms of repair and providing feedback to the origin of the defect. The purpose of this paper is to study these types of defects and the defect rates in design and assembly. The paper presents a web based questionnaire answered by 29 companies. The result shows that the defect rate (defects per product) spanned from 0.01 to 10. Also, design and assembly defects covered 46%, 23% respectively, of all occurred defects. A case study is also presented, performed at a company who recently implemented a modular architecture. In this company, defects from 5 700 integrated product architectures are compared with defects from 431 modular architectures. The average defect rate increased by 21.5% – from 0.65 to 0.79 – when a more modular architecture has been implemented. Furthermore, the study showed that the assembly defects have decreased while the design defects increased. The results presented in this paper will also support the development of the MPV (Module Property Verification) method which is briefly described.

Contributions of school design to adolescent identity formation : case studies of four Australian secondary schools

The paper presents a summary of the study that examined the relationship between school design and adolescent identity formation. Reviewing theories and empirical studies of identity development, three major processes involved in adolescent identity formation were identified: (1) separation or individuation process, (2) social integration or relational connectedness, and (3) developmental exploration. Two key characteristics of schools that support these identity formation processes were proposed: (1) having a supportive environment addressing needs for individuation and social integration, and (2) providing opportunities for developmental exploration. Implications of these characteristics for school design were studied through a review of research and practices of learning space design. Four secondary schools in Australia which represented an innovative approach to learning space design were then examined to provide insights into these design-related implications and better understand issues and challenges associated with them. The paper concludes with proposing five design principles which supports adolescent identity development through contributing to processes involved in identity formation.

Evaluating And Optimizing Sustainable Drainage Design To Maximize Multiple Benefits: Case Studies In China

In the past, the focus of drainage design was on sizing pipes and storages in order to provide sufficient network capacity. This traditional approach, together with computer software and technical guidance, had been successful for many years. However, due to rapid population growth and urbanisation, the requirements of a “good” drainage design have also changed significantly. In addition to water management, other aspects such as environmental impacts, amenity values and carbon footprint have to be considered during the design process. Going forward, we need to address the key sustainability issues carefully and practically. The key challenge of moving from simple objectives (e.g. capacity and costs) to complicated objectives (e.g. capacity, flood risk, environment, amenity etc) is the difficulty to strike a balance between various objectives and to justify potential benefits and compromises. In order to assist decision makers, we developed a new decision support system for drainage design. The system consists of two main components – a multi-criteria evaluation framework for drainage systems and a multi-objective optimisation tool. The evaluation framework is used for the quantification of performance, life-cycle costs and benefits of different drainage systems. The optimisation tool can search for feasible combinations of design parameters such as the sizes, order and type of drainage components that maximise multiple benefits. In this paper, we will discuss real-world application of the decision support system. A number of case studies have been developed based on recent drainage projects in China. We will use the case studies to illustrate how the evaluation framework highlights and compares the pros and cons of various design options. We will also discuss how the design parameters can be optimised based on the preferences of decision makers. The work described here is the output of an EngD project funded by EPSRC and XP Solutions.

Foundation Studies: Three Dimensional Design Project

Display of work accomplished by Section 10 and 18 of the 2004 Foundation students. Index to student work filed with the poster.

Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL-lactide-co-glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies

Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide-type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. in this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL-lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 2(3-1) factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration-centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 +/- 2.6 nm and the zeta potential -2.93 +/- 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded-PLGA-NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC-loaded PLGA-NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.