Computational design of self-assembling proteins and protein-DNA nanowires

Computational protein design (CPD) is a burgeoning field that uses a physical-chemical or knowledge-based scoring function to create protein variants with new or improved properties. This exciting approach has recently been used to generate proteins with entirely new functions, ones that are not observed in naturally occurring proteins. For example, several enzymes were designed to catalyze reactions that are not in the repertoire of any known natural enzyme. In these designs, novel catalytic activity was built de novo (from scratch) into a previously inert protein scaffold. In addition to de novo enzyme design, the computational design of protein-protein interactions can also be used to create novel functionality, such as neutralization of influenza. Our goal here was to design a protein that can self-assemble with DNA into nanowires. We used computational tools to homodimerize a transcription factor that binds a specific sequence of double-stranded DNA. We arranged the protein-protein and protein-DNA binding sites so that the self-assembly could occur in a linear fashion to generate nanowires. Upon mixing our designed protein homodimer with the double-stranded DNA, the molecules immediately self-assembled into nanowires. This nanowire topology was confirmed using atomic force microscopy. Co-crystal structure showed that the nanowire is assembled via the desired interactions. To the best of our knowledge, this is the first example of a protein-DNA self-assembly that does not rely on covalent interactions. We anticipate that this new material will stimulate further interest in the development of advanced biomaterials.

Topology optimization of silicon anode structures for lithium-ion battery applications

This thesis presents a topology optimization methodology for the systematic design of optimal multifunctional silicon anode structures in lithium-ion batteries. In order to develop next generation high performance lithium-ion batteries, key design challenges relating to the silicon anode structure must be addressed, namely the lithiation-induced mechanical degradation and the low intrinsic electrical conductivity of silicon. As such, this work considers two design objectives of minimum compliance under design dependent volume expansion, and maximum electrical conduction through the structure, both of which are subject to a constraint on material volume. Density-based topology optimization methods are employed in conjunction with regularization techniques, a continuation scheme, and mathematical programming methods. The objectives are first considered individually, during which the iteration history, mesh independence, and influence of prescribed volume fraction and minimum length scale are investigated. The methodology is subsequently extended to a bi-objective formulation to simultaneously address both the compliance and conduction design criteria. A weighting method is used to derive the Pareto fronts, which demonstrate a clear trade-off between the competing design objectives. Furthermore, a systematic parameter study is undertaken to determine the influence of the prescribed volume fraction and minimum length scale on the optimal combined topologies. The developments presented in this work provide a foundation for the informed design and development of silicon anode structures for high performance lithium-ion batteries.

A new low-power highly linear mixer design using differential derivative superposition

This paper presents the analysis and design of a new low power and highly linear mixer topology based on a newly reported differential derivative superposition method. Volterra series and harmonic balance are employed to investigate its linearisation mechanism and to optimise the design. A prototype mixer has been designed and is being implemented in 0.18μm CMOS technology. Simulation shows this mixer achieves 19.7dBm IIP3 with 10.5dB conversion gain, 13.2dB noise figure at 2.4GHz and only 3.8mW power consumption. This performance is competitive with already reported mixers.

Towards topology-free optimization - An application to turbine internal cooling geometries

The application of automated design optimization to real-world, complex geometry problems is a significant challenge - especially if the topology is not known a priori like in turbine internal cooling. The long term goal of our work is to focus on an end-to-end integration of the whole CFD Process, from solid model through meshing, solving and post-processing to enable this type of design optimization to become viable & practical. In recent papers we have reported the integration of a Level Set based geometry kernel with an octree-based cut- Cartesian mesh generator, RANS flow solver, post-processing & geometry editing all within a single piece of software - and all implemented in parallel with commodity PC clusters as the target. The cut-cells which characterize the approach are eliminated by exporting a body-conformal mesh guided by the underpinning Level Set. This paper extends this work still further with a simple scoping study showing how the basic functionality can be scripted & automated and then used as the basis for automated optimization of a generic gas turbine cooling geometry. Copyright © 2008 by W.N.Dawes.

Towards a fast electro-thermo-mechanical IGBT/Diode simulation framework for design of reliable power electronic converters

This paper describes a methodology that enables fast and reasonably accurate prediction of the reliability of power electronic modules featuring IGBTs and p-i-n diodes, by taking into account thermo-mechanical failure mechanisms of the devices and their associated packaging. In brief, the proposed simulation framework performs two main tasks which are tightly linked together: (i) the generation of the power devices' transient thermal response for realistic long load cycles and (ii) the prediction of the power modules' lifetime based on the obtained temperature profiles. In doing so the first task employs compact, physics-based device models, power losses lookup tables and polynomials and combined material-failure and thermal modelling, while the second task uses advanced reliability tests for failure mode and time-to-failure estimation. The proposed technique is intended to be utilised as a design/optimisation tool for reliable power electronic converters, since it allows easy and fast investigation of the effects that changes in circuit topology or devices' characteristics and packaging have on the reliability of the employed power electronic modules. © 2012 IEEE.

Tailored seeding geometries for the multi-fidelity design of compression systems

Design optimisation of compressor systems is a computationally expensive problem due to the large number of variables, complicated design space and expense of the analysis tools. One approach to reduce the expense of the process and make it achievable in industrial timescales is to employ multi-fidelity techniques, which utilise more rapid tools in conjunction with the highest fidelity analyses. The complexity of the compressor design landscape is such that the starting point for these optimisations can influence the achievable results; these starting points are often existing (optimised) compressor designs, which form a limited set in terms of both quantity and diversity of the design. To facilitate the multi-fidelity optimisation procedure, a compressor synthesis code was developed which allowed the performance attributes (e.g. stage loadings, inlet conditions) to be stipulated, enabling the generation of a variety of compressors covering a range of both design topology and quality to act as seeding geometries for the optimisation procedures. Analysis of the performance of the multi-fidelity optimisation system when restricting its exploration space to topologically different areas of the design space indicated little advantage over allowing the system to search the design space itself. However, comparing results from optimisations started from seed designs with different aerodynamic qualites indicated an improved performance could be achieved by starting an optimisation from a higher quality point, and thus that the choice of starting point did affect the final outcome of the optimisations. Both investigations indicated that the performance gains through the optimisation were largely defined by the early exploration of the design space where the multi-fidelity speedup could be exploited, thus extending this region is likely to have the greatest effect on performance of the optimisation system. © 2013 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

Tailored seeding geometries for the multi-fidelity design of compression systems

Design optimisation of compressor systems is a computationally expensive problem due to the large number of variables, complicated design space and expense of the analysis tools. One approach to reduce the expense of the process and make it achievable in industrial timescales is to employ multi-fidelity techniques, which utilise more rapid tools in conjunction with the highest fidelity analyses. The complexity of the compressor design landscape is such that the starting point for these optimisations can influence the achievable results; these starting points are often existing (optimised) compressor designs, which form a limited set in terms of both quantity and diversity of the design. To facilitate the multi-fidelity optimisation procedure, a compressor synthesis code was developed which allowed the performance attributes (e.g. stage loadings, inlet conditions) to be stipulated, enabling the generation of a variety of compressors covering a range of both design topology and quality to act as seeding geometries for the optimisation procedures. Analysis of the performance of the multi-fidelity optimisation system when restricting its exploration space to topologically different areas of the design space indicated little advantage over allowing the system to search the design space itself. However, comparing results from optimisations started from seed designs with different aerodynamic qualites indicated an improved performance could be achieved by starting an optimisation from a higher quality point, and thus that the choice of starting point did affect the final outcome of the optimisations. Both investigations indicated that the performance gains through the optimisation were largely defined by the early exploration of the design space where the multi-fidelity speedup could be exploited, thus extending this region is likely to have the greatest effect on performance of the optimisation system. © 2012 AIAA.

Computational engineering design for micro-scale combustion devices: A thermally improved configuration

A multi-objective design optimisation study has been carried out with the objectives to improve the overall efficiency of the device and to reduce the fuel consumption for the proposed micro-scale combustor design configuration. In a previous study we identified the topology of the combustion chamber that produced improved behaviour of the device in terms of the above design criteria. We now extend our design approach, and we propose a new configuration by the addition of a micro-cooling channel that will improve the thermal behaviour of the design as previously suggested in literature. Our initial numerical results revealed an improvement of 2.6% in the combustion efficiency when we applied the micro-cooling channel to an optimum design configuration we identified from our earlier multi-objective optimisation study, and under the same operating conditions. The computational modelling of the combustion process is implemented in the commercial computational fluid dynamics package ANSYS-CFX using Finite Rate Chemistry and a single step hydrogen-air reaction. With this model we try to balance good accuracy of the combustion solution and at the same time practicality within the context of an optimisation process. The whole design system comprises also the ANSYS-ICEM CFD package for the automatic geometry and mesh generation and the Multi-Objective Tabu Search algorithm for the design space exploration. We model the design problem with 5 geometrical parameters and 3 operational parameters subject to 5 design constraints that secure practicality and feasibility of the new optimum design configurations. The final results demonstrate the reliability and efficiency of the developed computational design system and most importantly we assess the practicality and manufacturability of the revealed optimum design configurations of micro-combustor devices. Copyright © 2013 by ASME.

BRITE: Universal Topology Generation from a User's Perspective

Effective engineering of the Internet is predicated upon a detailed understanding of issues such as the large-scale structure of its underlying physical topology, the manner in which it evolves over time, and the way in which its constituent components contribute to its overall function. Unfortunately, developing a deep understanding of these issues has proven to be a challenging task, since it in turn involves solving difficult problems such as mapping the actual topology, characterizing it, and developing models that capture its emergent behavior. Consequently, even though there are a number of topology models, it is an open question as to how representative the topologies they generate are of the actual Internet. Our goal is to produce a topology generation framework which improves the state of the art and is based on design principles which include representativeness, inclusiveness, and interoperability. Representativeness leads to synthetic topologies that accurately reflect many aspects of the actual Internet topology (e.g. hierarchical structure, degree distribution, etc.). Inclusiveness combines the strengths of as many generation models as possible in a single generation tool. Interoperability provides interfaces to widely-used simulation and visualization applications such as ns and SSF. We call such a tool a universal topology generator. In this paper we discuss the design, implementation and usage of the BRITE universal topology generation tool that we have built. We also describe the BRITE Analysis Engine, BRIANA, which is an independent piece of software designed and built upon BRITE design goals of flexibility and extensibility. The purpose of BRIANA is to act as a repository of analysis routines along with a user–friendly interface that allows its use on different topology formats.

THEORY AND DESIGN OF A TUNABLE QUASI-LUMPED QUADRATURE COUPLER

In this article, we present the theory and a design methodology for a unable Quasi-Lumped Quadrature Coupler (QLQC). Because of its topology, the coupler is simply reconfigured by switching the bias of two varactor diodes via a very simple DC bias circuitry. No additional capacitors or inductors are required. A prototype at 3.5 GHz is etched on a 0.130-mm-thick layer substrate with a dielectric material of relative permittivity of 2.22. The simulated and measured scattering parameters are, presented. (c) 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 2219-2222 2009: Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24526

Allometric analysis of Sitka spruce branches:Mechanical versus hydraulic design principles

The geometry of tree branches can have considerable effect on their efficiency in terms of carbon export per unit carbon investment in structure. The purpose of this study was to evaluate different design criteria using data describing the form of Picea sitchensis branches. Allometric analysis of the data suggests that resources are distributed to favour shoots with the greatest opportunity for extension into new space, with priority to the extension of the leader. The distribution of allometric relations of links (branch elements) was tested against two models: the pipe model, based on hydraulic transport requirements, and a static load model based on the requirement of shoots to provide mechanical resistance to static loads. Static load resistance required the load parameter to be proportional to the link radius raised to the power of 4. This was shown to be true within a 95% statistical confidence limit. The pipe model would require total distal length to be proportional to link radius squared but the measured branches did not conform well to this model. The comparison suggests that the diameters of branch elements were more related to the requirements for mechanical load. The cost of following a hydraulic design principle (the pipe model) in terms of mechanical efficiency was estimated and suggested that the pipe model branch would not be mechanically compromised but would use structural resources inefficiently. Resource allocation among branch elements was found to be consistent with mechanical stability criteria but also indicated the possibility of allocation based on other criteria, such as potential light interception by shoots. The evidence suggests that whilst branch topology increments by reiteration of units of morphogenesis, the geometry follows a functional design pattern.

Design technique for mm-wave IC realization of the load network of switched-mode class-EF power amplifier

Analysis and synthesis of the new Class-EF power amplifier (PA) are presented in this paper. The proposed circuit offers means to alleviate some of the major issues faced by existing Class-EF and Class-EF PAs, such as (1) substantial power losses due to parasitic resistance of the large inductor in the Class-EF load network, (2) unpredictable behaviour of practical lumped inductors and capacitors at harmonic frequencies, and (3) deviation from ideal Class-EF operation mode due to detrimental effects of device output inductance at high frequencies. The transmission-line load network of the Class-EF PA topology elaborated in this paper simultaneously satisfies the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Furthermore, an elegant solution using an open and short-circuit stub arrangement is suggested to overcome the problem encountered in the mm-wave IC realizations of the Class-EF PA load network due to lossy quarter-wave line. © 2010 IEICE Institute of Electronics Informati.

Managing Equivalent Representations of Design and Analysis Models

There is a requirement for better integration between design and analysis tools, which is difficult due to their different objectives, separate data representations and workflows. Currently, substantial effort is required to produce a suitable analysis model from design geometry. Robust links are required between these different representations to enable analysis attributes to be transferred between different design and analysis packages for models at various levels of fidelity.

This paper describes a novel approach for integrating design and analysis models by identifying and managing the relationships between the different representations. Three key technologies, Cellular Modeling, Virtual Topology and Equivalencing, have been employed to achieve effective simulation model management. These technologies and their implementation are discussed in detail. Prototype automated tools are introduced demonstrating how multiple simulation models can be linked and maintained to facilitate seamless integration throughout the design cycle.

Controlling Surface Topology and Functionality of Electrospun Fibers on the Nanoscale using Amphiphilic Block Copolymers To Direct Mesenchymal Progenitor Cell Adhesion

Surface patterning in three dimensions is of great importance in biomaterials design for controlling cell behavior. A facile one-step functionalization of biodegradable PDLLA fibers using amphiphilic diblock copolymers is demonstrated here to systematically vary the fiber surface composition. The copolymers comprise a hydrophilic poly[oligo(ethylene glycol) methacrylate] (POEGMA), poly[(2-methacryloyloxy)ethyl phosphorylcholine] (PMPC), or poly[2-(dimethylamino)ethyl methacrylate)] (PDMAEMA) block and a hydrophobic poly(l-lactide) (PLA) block. The block copolymer-modified fibers have increased surface hydrophilicity compared to that of PDLLA fibers. Mixtures of PLAPMPC and PLAPOEGMA copolymers are utilized to exploit microphase separation of the incompatible hydrophilic PMPC and POEGMA blocks at the fiber surface. Conjugation of an RGD cell-adhesive peptide to one hydrophilic block (POEGMA) using thiol-ene chemistry produces fibers with domains of cell-adhesive (POEGMA) and cell-inert (PMPC) sites, mimicking the adhesive properties of the extracellular matrix (ECM). Human mesenchymal progenitor cells (hES-MPs) showed much better adhesion to the fibers with surface-adhesive heterogeneity compared to that to fibers with only adhesive or only inert surface chemistries.