Set Of Design Rules Research Articles

Synthetic tetracycline-inducible regulatory networks: computer-aided design of dynamic phenotypes

BackgroundTightly regulated gene networks, precisely controlling the expression of protein molecules, have received considerable interest by the biomedical community due to their promising applications. Among the most well studied inducible transcription systems are the tetracycline regulatory expression systems based on the tetracycline resistance operon of Escherichia coli, Tet-Off (tTA) and Tet-On (rtTA). Despite their initial success and improved designs, limitations still persist, such as low inducer sensitivity. Instead of looking at these networks statically, and simply changing or mutating the promoter and operator regions with trial and error, a systematic investigation of the dynamic behavior of the network can result in rational design of regulatory gene expression systems. Sophisticated algorithms can accurately capture the dynamical behavior of gene networks. With computer aided design, we aim to improve the synthesis of regulatory networks and propose new designs that enable tighter control of expression.ResultsIn this paper we engineer novel networks by recombining existing genes or part of genes. We synthesize four novel regulatory networks based on the Tet-Off and Tet-On systems. We model all the known individual biomolecular interactions involved in transcription, translation, regulation and induction. With multiple time-scale stochastic-discrete and stochastic-continuous models we accurately capture the transient and steady state dynamics of these networks. Important biomolecular interactions are identified and the strength of the interactions engineered to satisfy design criteria. A set of clear design rules is developed and appropriate mutants of regulatory proteins and operator sites are proposed.ConclusionThe complexity of biomolecular interactions is accurately captured through computer simulations. Computer simulations allow us to look into the molecular level, portray the dynamic behavior of gene regulatory networks and rationally engineer novel ones with useful applications. We are able to propose, test and accept or reject design principles for each network. Guided by simulations, we develop a set of design principles for novel tetracycline-inducible networks.

Performance of Optical OFDM in Ultralong-Haul WDM Lightwave Systems

We show, using simulations, that a combination of orthogonal frequency division multiplexing (OFDM) and optical single sideband modulation can be used to compensate for chromatic dispersion in ultralong-haul wavelength-division multiplexed (WDM) systems. OFDM provides a high spectral efficiency, does not require a reverse feedback path for compensation, and has a better sensitivity than nonreturn to zero. This paper provides design rules for 800-4000-km optical-OFDM systems. The effects of WDM channel number and spacing, fiber dispersion, and input power per channel on the received Q are studied using extensive numerical simulations. These effects are summarized as a set of design rules

Integrated siRNA design based on surveying of features associated with high RNAi effectiveness

BackgroundShort interfering RNAs have allowed the development of clean and easily regulated methods for disruption of gene expression. However, while these methods continue to grow in popularity, designing effective siRNA experiments can be challenging. The various existing siRNA design guidelines suffer from two problems: they differ considerably from each other, and they produce high levels of false-positive predictions when tested on data of independent origins.ResultsUsing a distinctly large set of siRNA efficacy data assembled from a vast diversity of origins (the siRecords data, containing records of 3,277 siRNA experiments targeting 1,518 genes, derived from 1,417 independent studies), we conducted extensive analyses of all known features that have been implicated in increasing RNAi effectiveness. A number of features having positive impacts on siRNA efficacy were identified. By performing quantitative analyses on cooperative effects among these features, then applying a disjunctive rule merging (DRM) algorithm, we developed a bundle of siRNA design rule sets with the false positive problem well curbed. A comparison with 15 online siRNA design tools indicated that some of the rule sets we developed surpassed all of these design tools commonly used in siRNA design practice in positive predictive values (PPVs).ConclusionThe availability of the large and diverse siRNA dataset from siRecords and the approach we describe in this report have allowed the development of highly effective and generally applicable siRNA design rule sets. Together with ever improving RNAi lab techniques, these design rule sets are expected to make siRNAs a more useful tool for molecular genetics, functional genomics, and drug discovery studies.

The Liquid/Liquid Sedimentation Process: From Droplet Coalescence to Technologically Enhanced Water/Oil Emulsion Gravity Separators: A Review

Crude oil is nearly always produced along with water in the form of water/crude oil emulsions. Gravity settlers are the most common technology to separate these dispersions. A short description is given of the coalescence mechanism (droplet collision, film drainage, film rupture). Three micromechanical sedimentation models (Hartland, Lobo, Henschke) and one set of design rules (Polderman) are described. IFP experimental data are presented that confirm the difference between sedimentation‐based and coalescence‐based models. Technological enhancements used in order to accelerate and/or increase the separation (heating, chemical demulsifiers, mechanical barriers, electrocoalescence, ultrasound, microwaves) are presented.

The institutional economics of sharing biological information

Within the field of the governance of biodiversity, initiatives for sharing knowledge through networking distributed databases have emerged, operating both on a global scale (such as the Global Biodiversity Information Facility connecting worldwide biodiversity resources in a searchable database portal) and in more focused issue networks (such as the European Human Frozen Tumour Tissue Bank). In this article, I analyse the institutional conditions for the development of these initiatives in the particular case of microbiological resources. Two main results come out of this analysis. First, microbiological information has to be considered as a complex good, having both public good and common pool resources aspects. Second, to solve the incentive problems for this complex good, we have to go beyond a static conception of efficiency (favouring economic incentives through the allocation of intellectual property rights) and adopt a dynamic framework (geared towards the enforcement of norms of cooperation in a context of changing social preferences and processes of knowledge acquisition throughout the entire innovation chain). Building on the methodologies of successful research programmes on dynamic efficiency in other fields of new institutional economics, I discuss a framework for defining a robust set of design rules for the governance of the microbiological commons.

Structural behavior of lapped cold-formed steel Z sections with generic bolted configurations

In order to improve the buildability of cold-formed steel structures, a series of research and development projects have been undertaken by the authors to study the structural behavior of bolted moment connections between cold-formed steel sections. As one of the major applications of cold-formed steel sections in building construction is modern roof structures with multi-span purlin systems, an extensive experimental and theoretical investigation on the structural behavior of lapped moment connections between cold-formed steel Z sections was carried out. Both generic configurations with high structural efficiency were adopted, namely, Config. W4 and W6, in which only the webs of the sections were bolted together for easy installation. Moreover, an analysis and design method was proposed to assess both the moment resistance and the effective flexural rigidity of the generic lapped connections. The research work aims to provide understanding on the structural behavior of cold-formed steel Z sections with lapped connections, and hence, to develop a set of rational design rules for multi-span purlin systems with overlaps. In order to verify the applicability of the proposed analysis and design method for other commonly adopted connection configurations, namely, Config. W2F2 and W4F2 where bolts were installed to both section webs and flanges within the lapped connections, an experimental and theoretical investigation on a total of 12 one point load tests on lapped cold-formed steel Z sections were carried out. Among all tests, section failure under combined bending and shear at the ends of lap was found to be critical while twisting of the lapped Z sections was apparent throughout the entire deformation ranges. In general, the structural behavior of lapped connections with Config. W2F2 and W4F2 was found to be similar to those with Config. W4 and W6. Moreover, the formulation of the proposed analysis and design method was modified to accommodate the presence of the flange bolts, and back analysis of the lapped Z sections against combined bending and shear using the proposed method was performed. After careful calibration against test data, the method was shown to be structurally adequate and efficient for lapped connections with Config. W2F2 and W4F2. Moreover, simple design expressions were also proposed for the evaluation of effective flexural rigidities of the lapped connections. Comparison on the structural behavior between the two sets of connection configurations was also presented.

Mass customation of foot orthosis for rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease, which can cause pain, stiffness, and swelling in the joints of hands and feet. The foot is a major site for RA involvement and a major source of disability resulting from this disease. This paper introduces research which aims to create a mass customisation process for customised orthoses for patients with RA. 3D laser scanning, and gait analysis will be used to generate the orthosis geometry and rapid manufacturing, namely the selective laser sintering (SLS) process, will be used to produce the orthoses. The SLS process enables the incorporation of compositional functional elements, such as locally adjusted stiffness or flexibility, into the orthosis design. The process involved two central elements. The first was a literature survey to identify orthotic design rules for foot impairments in RA. This survey will form a platform for the design rule development and will be complemented by data obtained from two patient trials. The second is a virtual three-segment foot model, created in Anybody dynamics modelling software which can be motivated by data measured from patients using 3D motion capture and force plate systems. Once the measured data has been applied to the model, a virtual insole can be used to simulate the effects of various features in the orthosis. Considerable variation was noted in the literature for types of material, design and methods of orthotic construction. Pressure redistribution using cushioning materials was consistently mapped to painful deformed joints. Orthoses with contoured surfaces, either customor mass produced in thermoplastic materials of varying stiffness and density were mapped to joint motion control and deformity prevention. The paper will also describe applying patient gait data to the Anybody model, and then altering the gait pattern by applying the insole model. Future work will also be discussed. Introduction The purpose of this project is to create a process that will produce customised foot orthoses for rheumatoid arthritis sufferers. Currently, the production of foot orthosis is time-consuming, and expensive, with delivery times up to six weeks, during which the disease can alter the foot further. Improved clinical outcomes can be connected to custom foot orthoses, when compared against mass-produced orthosis. The novelty of this project is the application of mass-customisation principles and layermanufacturing technology to existing clinical processes. Currently the design of orthoses is very much a craft and there are only a few standardised procedures when subscribing them. To assist the design, a set of design rules and a virtual gait model will be created.

Photonic information processing needs quantum design rules

In the century since Einstein postulated light’s quantum nature—an event celebrated last year, along with SPIE’s 50th birthday—the quantum revolution has progressed from formalizing the mathematical theory of the electron and photon, to a second wave that uses quantum phenomena for new information-processing technologies. These applications are found in fields as diverse as communications, cryptography, computing, and even imaging. Since photons are the de facto information-encoding entity, this means photonic information processing often amounts to quantum information processing, which can be carried out on chips fabricated with very large scale integration (VLSI) techniques, such as the array of single-photon detectors shown in Figure 1, for significantcost reduction.Our experiencewith VLSI has taught us the importance of having good rules that abstract away the underlying physics and allow engineers to design chips. This inspired us to consider an analogous set of quantum design rules (QDRs) for VLSI photonics.2, 3

Active control of the depletion boundary layers in microfluidic electrochemical reactors

In this paper, we describe three methods to improve the performance of pressure-driven laminar flow-based microreactors by manipulating reaction-depletion boundary layers to overcome mass transfer limitations at reactive surfaces on the walls, such as electrodes. The transport rate of the reactants to the reactive surfaces is enhanced by (i) removing the depleted zone through multiple periodically-placed outlets; (ii) adding fresh reactants through multiple periodically-placed inlets along the reactive surface; or (iii) producing a spiraling, transverse flow through the integration of herringbone ridges along the channel walls. For approaches (i) and (ii), the network of microfluidic channels needs to be designed such that under the operating conditions used the right amount of boundary layer at each outlet or inlet is removed or replenished, respectively. Here, we report a set of design rules, derived with the help of a fluidic resistance circuit model, to aid in the design of appropriate microfluidic networks. Also, the actual enhancement of the performance of the electrochemical microreactor, i.e. chemical conversion efficiency, using multiple inlets, multiple outlets, or herringbone ridges is reported.

Design of Peptides with α,β-Dehydro Residues: Synthesis, Crystal Structure and Molecular Conformation of a Peptide N-Boc-Phe-ΔPhe-Ile-OCH3

To develop a complete set of design rules with α,β-dehydro residues, a tripeptide N-Boc-Phe-ΔPhe-Ile-OCH3 was synthesized. The synthesis was carried out in solution phase using azlactone procedure. The three-dimensional structure of the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.085. The structure contains three peptide molecules in the asymmetric unit. In all the three crystallographically independent molecules ΔPhe residue adopts one of the three conformations that have been reported for a ΔPhe residue. The overall conformations of three peptide molecules in the asymmetric unit are not similar. Two out of three crystallographically independent molecules adopt type II β-turn conformations whereas the third molecule is found having the characteristic S-shaped conformation in which the values of dihedral angles φ, ψ have opposite signs alternately. One of these two types of conformations has been observed when a ΔPhe is introduced at (i+2) position of a tetrapeptide. The β-turn conformation is stabilized by a 4→1 hydrogen bond where the hydrophobic side chains of residues at (i+1) and (i+3) positions stabilized the unfolded conformation with van der Waals interactions. The three independent molecules are locked together by three hydrogen bonds between molecules A and B and two hydrogen bonds between molecules B and C.

Analysis of bolted moment connections in cold-formed steel beam–column sub-frames

An extensive experimental investigation on bolted moment connections between cold-formed steel sections was carried out, and a total of 16 internal and external beam–column sub-frames with various connection configurations were tested under lateral loads. It is found that for those six beam–column sub-frames with large bolt pitches and thick gusset plates in the connections, flexural failure of connected sections is always critical. The moment resistances of the connections attain at least 85% of the moment capacities of the connected sections. This paper presents a theoretical investigation for predicting the structural behaviour of bolted moment connections between cold-formed steel sections. An analysis and design method for internal force distribution of the connections is presented, and hence a set of design rules for section failure of connected sections under combined bending and shear is proposed. Moreover, a non-linear finite element model of the beam–column sub-frames incorporating the effect of semi-rigid joints is also presented. On the basis of the measured moment joint rotation curves of the bolted moment connections, the overall lateral load–deflection curves of the sub-frames are predicted, and they are found to follow closely the curves obtained from tests. Furthermore, a semi-empirical formula for flexibility prediction of the bolted moment connections is also proposed after careful calibration against test data. It is demonstrated that the proposed rules are highly effective for predicting the structural performance of cold-formed steel frames with bolted moment connections. Hence, structural engineers are encouraged to design and build cold-formed steel structures with bolted moment connections to achieve practical and efficient construction.

A Synthesis System for Analog Circuits Based on Evolutionary Search and Topological Reuse

We present a method for automated synthesis of analog circuits using evolutionary search and a set of circuit design rules based on topological reuse. The system requires only moderate expert knowledge on part of the user. It allows circuit size, circuit topology, and device values to evolve. The circuit representation scheme employs a topological reuse-based approach-it uses commonly used subcircuits for analog design as inputs and utilizes these to create the final circuit. The connectivity between these blocks is governed by a well-defined set of rules and the scheme is capable of representing most standard analog circuit topologies. The system operation consists of two phases-in the first phase, the circuit size and topology are evolved. A limited amount of device sizing also occurs in this phase. The second phase consists entirely of device value optimization. The design of the evaluation function-which evaluates each generated circuit using SPICE simulations-has also been automated to a great extent. The evaluation function is generated automatically depending on a behavioral description of the circuit. We present several experimental results obtained using this scheme, including two types of comparators, two types of oscillators, and an XOR logic gate. The generated circuits closely resemble hand designed circuits. The computational needs of the system are modest.

Extending aggressive low-k1 design rule requirements for 90 and 65 nm nodes via simultaneous optimization of numerical aperture, illumination and optical proximity correction

It has been a challenge for the lithography process to meet aggressive integrated circuit design rule requirements for 90 nm and upcoming 65 nm technology nodes under low-k1 patterning constraints. The geometric design rules are largely governed by numerical aperture (NA), illumination settings, and optical proximity correction (OPC) for any resolution enhancement technique-applied mask. A set of process feasible design rule criteria is explored based on state-of-the-art microprocessor chip that contains three different types of circuit design-standard library cell (SLC), random logic (RML), and static random access memory (SRAM). The critical design rule criteria to keep higher packing density for SRAM involve: achievable minimum pitch, sufficient area of contact-landing pad, minimum line-end shortening (LES) to ensure poly end-cap and preferably optimum pitch for placement of Scattering BarTM (SB). The goal is to achieve printing of ever-smaller critical dimension (CD) with greater CD uniformity control for RML. SLC should be designed with comparable criteria to both RML and SRAM devices. Hence, the design rule constraints for CD, space, line-end, minimum pitch and SB placement for SLC cell are critically confined. Unlike traditional method of assuming a linear scaling for the design rule set, achievable design rule criteria is explored for very low k1-imaging by simultaneously optimizing NA, illumination settings and OPC (for optimum placement of SB) for a calibrated process. This is done by analyzing CD uniformity control and maximum overlapped process window for critical lines, spaces and line-ends with the respective k1 factor for three types of circuits. A feasible set of design rules for 90 nm node with k1 as low as 0.36 can be obtained using 6% attenuated phase shift mask (attPSM) with 6% exposure latitude at 400 nm of overlapped depth of focus.

Analysis and design of lapped connections between cold-formed steel Z sections

This paper presents an analysis and design method for lapped connections between cold-formed steel Z sections after careful calibration against test data obtained from a total of 26 one point-load tests on lapped connections. Based on the experimental observations on the lapped connection tests where combined bending and shear is always critical in the cross-sections at the end of laps, an analysis method is proposed to evaluate all the internal forces within the lapped connections. Once the co-existing moments and shear forces in the lapped connections are evaluated, the critical sections are readily checked against combined bending and shear using codified design rules. Moreover, design expressions are also proposed for the evaluation of effective flexural rigidities of lapped connections with various bolt configurations against practical lap length to section depth ratios. Consequently, the structural behaviour of lapped sections between cold-formed steel Z sections in terms of strength and stiffness is quantified rationally for general design. The research project aims to provide understanding to the structural performance of lapped connections between cold-formed steel Z sections, and hence, to develop a set of rational design rules for multi-span purlin systems with overlaps in modern roof construction.

Dielectrophoretic Traps for Single-Particle Patterning

We present a novel microfabricated dielectrophoretic trap designed to pattern large arrays of single cells. Because flowing away untrapped cells is often the rate-limiting step during cell patterning, we designed the trap to be strong enough to hold particles against practical flow rates. We experimentally validated the trap strength by measuring the maximum flow rate that polystyrene beads could withstand while remaining trapped. These bead experiments have shown excellent agreement with our model predictions, without the use of fitting parameters. The model was able to provide us with a fundamental understanding of how the traps work, and additionally allowed us to establish a set of design rules for optimizing the traps for a wide range of cell sizes. We provide the foundations for an enabling technology that can be used to pattern cells in unique ways, allowing us to do novel cell biology experiments at the microscale.

A generic analytical model for micro-diaphragm pumps with active valves

We present a fully analytical model for micro-diaphragm pumps with active valves, based on the peristaltic working principle. Our model is suited for very fast as well as for very slow actuation mechanisms. Therefore it can be applied to a variety of actuation principles, e.g. piezoelectric, pneumatic, thermo-pneumatic or pre-stressed shape memory actuation. We show that the dynamics of this kind of micropump can be fully described by a lumped element approach taking only the mechanical behaviour of the diaphragms and the viscous losses at the valves into account. The full flow versus frequency and backpressure characteristic is derived. Our model is capable of predicting the maximum achievable flow rate and the maximum sustainable backpressure of micro-diaphragm pumps with active valves. Different modes of operation, which are distinguished by the speed of the actuation mechanism, the pressure history inside the pump and the applied driving scheme, are identified. We show that micro-diaphragm pumps with active valves generally suffer from a linear dependence of the flow rate on the applied backpressure. This fact, which is already known from micropumps with passive valves, is remarkable, because it is in contradiction to the characteristics of macroscopic peristaltic pumps. A set of design rules for the dimensioning of the valves in dependence on the actuation force and the desired hydrodynamic characteristics (maximum flow rate and maximum sustainable backpressure) are derived. Our theoretical results are proven by experimental results of our piezoelectrically actuated micropump. A maximum flow rate of 1.4 ml min−1 and a maximum sustainable backpressure of 40 kPa were achieved.

Novel Experimental Design for Steady-state Processes: A Systematic Bayesian Approach for Enzymes, Drug Transport, Receptor Binding, Continuous Culture and Cell Transport Kinetics

We demonstrate that a Bayesian approach (the use of prior knowledge) to the design of steady-state experiments 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 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. It is equally applicable to enzymes, drug transport, receptor binding, microbial culture and cell transport kinetics.

Design rules for slanted-angle polarization rotators

A simple and general set of design rules for slanted-angle polarization-rotating waveguides is presented in this paper. These design rules are employed to construct single-mode SOI polarization rotators that offer significant advantages in conversion efficiency, optical loss, fabrication tolerance, spectral response and spatial dimensions relative to III-V components.

Substituent effects on the stability of extended benzylic carbocations: a computational study of conjugation

A set of design rules for the prediction of relative stabilities of methoxy substituted naphthyl methyl carbocations are presented based on a series of DFT calculations. The peri-effect, over-crowding, substitutions on the ring carrying the CH(2)(+) group and substitution on the opposite ring are the principal factors that influence the stability of the carbocations. All of these factors have to be taken simultaneously into account. The most pronounced destabilization occurs when the methyl part of the methoxy substituent lies out of the plane of the aromatic core because this causes the resonance stabilization of the carbocation to become hindered. The performance of the DFT-calculations was assessed on the results of a G3(MP2)//B3LYP calculation-a method that is known to predict energies to within chemical accuracy. These values were found to compare well with those obtained at the B3LYP/6-31G(d) level. Thus, a computationally inexpensive method such as the B3LYP/6-31G(d) might prove to be a powerful tool in the design of future complex extended aromatic systems.

A rough set approach to design concept analysis in a design chain

The inherent dynamic relationships among design tasks performed concurrently at different organizations characterize the complexities of a design chain where designers with diverse expertise need to collaborate across organizational boundaries. To ensure timely completion of inter-related design tasks, metrics to facilitate the early evaluation of design concepts are crucial. The ability to evaluate and select suitable design concepts at an early stage will ensure better solutions and greater savings in time and effort further downstream. This paper proposes a new approach based on the rough set theory to design concept analysis. The approach aims at early detection of design inadequacy. A so-called information system is constructed using the information gleaned from design concepts and design capabilities, and analyzed using the rough set theory to derive a set of design rules for design concept analysis. The approach embodies a technique for handling attributes with unavailable information, which is a frequent occurrence in design. This paper presents details of the proposed approach, the novel technique, and a case study.