Design, synthesis and spectroscopic characterisation of a focused library based on the polyandrocarpamine natural product scaffold

A focused library based on the marine natural products polyandrocarpamines A (1) and B (2) has been designed and synthesised using parallel solution-phase chemistry. In silico physicochemical property calculations were performed on synthetic candidates in order to optimise the library for drug discovery and chemical biology. A library of ten 2-aminoimidazolone products (3–12) was prepared by coupling glycocyamidine and a variety of aldehydes using a one-step stereoselective aldol condensation reaction under microwave conditions. All analogues were characterised by NMR, UV, IR and MS. The library was evaluated for cytotoxicity towards the prostate cancer cell lines, LNCaP, PC-3 and 22Rv1.

A pseudo-marginal sequential Monte Carlo algorithm for random effects models in Bayesian sequential design

A computationally efficient sequential Monte Carlo algorithm is proposed for the sequential design of experiments for the collection of block data described by mixed effects models. The difficulty in applying a sequential Monte Carlo algorithm in such settings is the need to evaluate the observed data likelihood, which is typically intractable for all but linear Gaussian models. To overcome this difficulty, we propose to unbiasedly estimate the likelihood, and perform inference and make decisions based on an exact-approximate algorithm. Two estimates are proposed: using Quasi Monte Carlo methods and using the Laplace approximation with importance sampling. Both of these approaches can be computationally expensive, so we propose exploiting parallel computational architectures to ensure designs can be derived in a timely manner. We also extend our approach to allow for model uncertainty. This research is motivated by important pharmacological studies related to the treatment of critically ill patients.

Building energy simulation and parallel computing : opportunities and challenges

Increased focus on energy cost savings and carbon footprint reduction efforts improved the visibility of building energy simulation, which became a mandatory requirement of several building rating systems. Despite developments in building energy simulation algorithms and user interfaces, there are some major challenges associated with building energy simulation; an important one is the computational demands and processing time. In this paper, we analyze the opportunities and challenges associated with this topic while executing a set of 275 parametric energy models simultaneously in EnergyPlus using a High Performance Computing (HPC) cluster. Successful parallel computing implementation of building energy simulations will not only improve the time necessary to get the results and enable scenario development for different design considerations, but also might enable Dynamic-Building Information Modeling (BIM) integration and near real-time decision-making. This paper concludes with the discussions on future directions and opportunities associated with building energy modeling simulations.

Design and synthesis of a screening library using the natural product scaffold 3-chloro-4-hydroxyphenylacetic acid

The fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (1) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. A 20-membered amide library (3–22) was generated by first converting 1 to methyl (3-chloro-4-hydroxyphenyl)acetate (2), then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. The structures of the synthetic analogues (3–22) were elucidated by spectroscopic data analysis. The structures of compounds 8, 12, and 22 were confirmed by single X-ray crystallographic analysis. All compounds were evaluated for cytotoxicity against a human prostate cancer cell line (LNCaP) and for antiparasitic activity toward Trypanosoma brucei brucei and Plasmodium falciparum and showed no significant activity at 10 μM. The library was also tested for effects on the lipid content of LNCaP and PC-3 prostate cancer cells, and it was demonstrated that the fluorobenzyl analogues (12–14) significantly reduced cellular phospholipid and neutral lipid levels.

Evolutionary optimization and game strategies for advanced multi-disciplinary design : applications to aeronautics and UAV design

Many complex aeronautical design problems can be formulated with efficient multi-objective evolutionary optimization methods and game strategies. This book describes the role of advanced innovative evolution tools in the solution, or the set of solutions of single or multi disciplinary optimization. These tools use the concept of multi-population, asynchronous parallelization and hierarchical topology which allows different models including precise, intermediate and approximate models with each node belonging to the different hierarchical layer handled by a different Evolutionary Algorithm. The efficiency of evolutionary algorithms for both single and multi-objective optimization problems are significantly improved by the coupling of EAs with games and in particular by a new dynamic methodology named “Hybridized Nash-Pareto games”. Multi objective Optimization techniques and robust design problems taking into account uncertainties are introduced and explained in detail. Several applications dealing with civil aircraft and UAV, UCAV systems are implemented numerically and discussed. Applications of increasing optimization complexity are presented as well as two hands-on test cases problems. These examples focus on aeronautical applications and will be useful to the practitioner in the laboratory or in industrial design environments. The evolutionary methods coupled with games presented in this volume can be applied to other areas including surface and marine transport, structures, biomedical engineering, renewable energy and environmental problems.

Design and fabrication of linear pixel arrays for organic photovoltaic modules to achieve scalable power output

We describe a design and fabrication method to enable simpler manufacturing of more efficient organic solar cell modules using a modified flat panel deposition technique. Many mini-cell pixels are individually connected to each other in parallel forming a macro-scale solar cell array. The pixel size of each array is optimized through experimentation to maximize the efficiency of the whole array. We demonstrate that integrated organic solar cell modules with a scalable current output can be fabricated in this fashion and can also be connected in series to generate a scalable voltage output.

Enriching architectural design education through interactive displays and local community engagement

Designers have a social responsibility to deal with the needs, issues, and problems that their clients and communities are confronted with. Students of design require opportunities to reflect on their role as social facilitators to develop an attitude towards community engagement through different phases and aspects of their careers. However, current design courses are challenged by compressed timeframes and fragmented scenarios of different academic requirements that do not actively teach community engagement. This paper outlines a participatory and technological approach that was employed to address these issues within the teaching of Architecture and Urban Design at the Queensland University of Technology, Brisbane, Australia. A multi-phase community based research project with actual stakeholders was implemented over a two-year period. Approximately 150 students in the final year of the Bachelor of Design-Architecture; 10 students in the Master of Architecture and 15 students in the Master of Design-Urban Design have informed and influenced each others’ learning through the teaching and research nexus facilitated by this project. The technical approach was implemented in form of a bespoke digital platform that supported the display and discussion of digital media on a series of interactive touch walls. The platform allowed students to easily upload their final designs onto large interactive surfaces, where visitors could explore the media and provide comments. Through the use of this technical platform and the introduction of neogeography, students have been able to broaden their level of interaction and support their learning experience through external structured and unstructured feedback from the local community. Students have not only been exposed to community representatives, but they also have been working in parallel on a specific case study providing each other, across different years and courses, material for reflection and data to structure their design activities.

SHAMP: An experimental shared memory multimicroprocessor system for performance evaluation of parallel algorithms

In this paper, the design and implementation of a single shared bus, shared memory multiprocessing system using Intel's single board computers is presented. The hardware configuration and the operating system developed to execute the parallel algorithms are discussed. The performance evaluation studies carried out on Image are outlined.

A study on bullock carts. Part 1. Engineering analysis of the two-wheel bullock cart design

An engineering analysis of the design of two-wheel bullock carts has been carried out with the aid of a mathematical model. Non-dimensional expressions for the pull and the neck load have been developed. In the first instance, the cart is assumed to be cruising at constant velocity on a terrain with the effective coefficient of rolling friction varying over a wide range (0.001 to 0.5) and the gradient varying between +0.2 to −0.2. Subsequently, the effect of inertia force due to an acceleration parallel to the ground is studied. In the light of this analysis, two modifications to the design of the cart have been proposed and the relative merits of the current designs and the proposed designs are discussed.

Design and testing of stand-specific bucking instructions for use on modern cut-to-length harvesters

This study addresses three important issues in tree bucking optimization in the context of cut-to-length harvesting. (1) Would the fit between the log demand and log output distributions be better if the price and/or demand matrices controlling the bucking decisions on modern cut-to-length harvesters were adjusted to the unique conditions of each individual stand? (2) In what ways can we generate stand and product specific price and demand matrices? (3) What alternatives do we have to measure the fit between the log demand and log output distributions, and what would be an ideal goodness-of-fit measure? Three iterative search systems were developed for seeking stand-specific price and demand matrix sets: (1) A fuzzy logic control system for calibrating the price matrix of one log product for one stand at a time (the stand-level one-product approach); (2) a genetic algorithm system for adjusting the price matrices of one log product in parallel for several stands (the forest-level one-product approach); and (3) a genetic algorithm system for dividing the overall demand matrix of each of the several log products into stand-specific sub-demands simultaneously for several stands and products (the forest-level multi-product approach). The stem material used for testing the performance of the stand-specific price and demand matrices against that of the reference matrices was comprised of 9 155 Norway spruce (Picea abies (L.) Karst.) sawlog stems gathered by harvesters from 15 mature spruce-dominated stands in southern Finland. The reference price and demand matrices were either direct copies or slightly modified versions of those used by two Finnish sawmilling companies. Two types of stand-specific bucking matrices were compiled for each log product. One was from the harvester-collected stem profiles and the other was from the pre-harvest inventory data. Four goodness-of-fit measures were analyzed for their appropriateness in determining the similarity between the log demand and log output distributions: (1) the apportionment degree (index), (2) the chi-square statistic, (3) Laspeyres quantity index, and (4) the price-weighted apportionment degree. The study confirmed that any improvement in the fit between the log demand and log output distributions can only be realized at the expense of log volumes produced. Stand-level pre-control of price matrices was found to be advantageous, provided the control is done with perfect stem data. Forest-level pre-control of price matrices resulted in no improvement in the cumulative apportionment degree. Cutting stands under the control of stand-specific demand matrices yielded a better total fit between the demand and output matrices at the forest level than was obtained by cutting each stand with non-stand-specific reference matrices. The theoretical and experimental analyses suggest that none of the three alternative goodness-of-fit measures clearly outperforms the traditional apportionment degree measure. Keywords: harvesting, tree bucking optimization, simulation, fuzzy control, genetic algorithms, goodness-of-fit

Design of a synchronous decade down counter

Digital positioning systems often require a down counter for their operation. Due to the necessity of particular logic sequences and control of individual terminals, the design of down counters for particular use is very essential. In this paper the design procedure and logic diagram for a synchronous decade down counter with parallel carry are presented.

An algebraic formulation of static isotropy and design of statically isotropic 6-6 Stewart platform manipulators

In this paper, we present an algebraic method to study and design spatial parallel manipulators that demonstrate isotropy in the force and moment distributions. We use the force and moment transformation matrices separately, and derive conditions for their isotropy individually as well as in combination. The isotropy conditions are derived in closed-form in terms of the invariants of the quadratic forms associated with these matrices. The formulation is applied to a class of Stewart platform manipulator, and a multi-parameter family of isotropic manipulators is identified analytically. We show that it is impossible to obtain a spatially isotropic configuration within this family. We also compute the isotropic configurations of an existing manipulator and demonstrate a procedure for designing the manipulator for isotropy at a given configuration. (C) 2008 Elsevier Ltd. All rights reserved.

Optimum design of cantilever sheet pile walls in sandy soils using inverse reliability approach

In this paper an approach for obtaining depth and section modulus of the cantilever sheet pile wall using inverse reliability method is described. The proposed procedure employs inverse first order reliability method to obtain the design penetration depth and section modulus of the steel sheet pile wall in order that the reliability of the wall against failure modes must meet a desired level of safety. Sensitivity analysis is conducted to assess the effect of uncertainties in design parameters on the reliability of cantilever sheet pile walls. The analysis is performed by treating back fill soil properties, depth of the water table from the top of the sheet pile wall, yield strength of steel and section modulus of steel pile as random variables. Two limit states, viz., rotational and flexural failure of sheet pile wall are considered. The results using this approach are used to develop a set of reliability based design charts for different coefficients of variation of friction angle of the backfill (5%, 10% and 15%). System reliability considerations in terms of series and parallel systems are also studied.

Parallel implementation of AutoDock

Computational docking of ligands to protein structures is a key step in structure-based drug design. Currently, the time required for each docking run is high and thus limits the use of docking in a high-throughput manner, warranting parallelization of docking algorithms. AutoDock, a widely used tool, has been chosen for parallelization. Near-linear increases in speed were observed with 96 processors, reducing the time required for docking ligands to HIV-protease from 81 min, as an example, on a single IBM Power-5 processor ( 1.65 GHz), to about 1 min on an IBM cluster, with 96 such processors. This implementation would make it feasible to perform virtual ligand screening using AutoDock.