The 'parallel bridge' and its relevance to biotechnology new ventures

A firm's competitive strategy and innovation processes are strongly influenced by, and must be responsive to, its competitive environment. This is nowhere more strongly evident than in the high technology industries. In the present work, case studies of biotechnology new ventures are presented. These studies illustrate how an initial market entry strategy of parallel competition (through creative imitation) has enabled several biotechnology start-ups to reduce their mortality risk. We coin the term ''parallel bridge'' to describe this strategy. The parallel bridge provides early cash flows which support research and development and provide time for new ventures to develop core competencies, including a capacity to produce second and third horizon products that will sustain longer term competitiveness.

A plasmonic 'ac Wheatstone bridge' circuit for high-sensitivity phase measurement and single-molecule detection

In this paper, a plasmonic “ac Wheatstone bridge” circuit is proposed and theoretically modeled for the first time. The bridge circuit consists of three metallic nanoparticles, shaped as rectangular prisms, with two nanoparticles acting as parallel arms of a resonant circuit and the third bridging nanoparticle acting as an optical antenna providing an output signal. Polarized light excites localized surface plasmon resonances in the two arms of the circuit, which generate an optical signal dependent on the phase-sensitive excitations of surface plasmons in the antenna. The circuit is analyzed using a plasmonic coupling theory and numerical simulations. The analyses show that the plasmonic circuit is sensitive to phase shifts between the arms of the bridge and has the potential to detect the presence of single molecules.

Integrated health prediction of bridge systems using dynamic object oriented Bayesian networks (DOOBNS)

The serviceability and safety of bridges are crucial to people’s daily lives and to the national economy. Every effort should be taken to make sure that bridges function safely and properly as any damage or fault during the service life can lead to transport paralysis, catastrophic loss of property or even casualties. Nonetheless, aggressive environmental conditions, ever-increasing and changing traffic loads and aging can all contribute to bridge deterioration. With often constrained budget, it is of significance to identify bridges and bridge elements that should be given higher priority for maintenance, rehabilitation or replacement, and to select optimal strategy. Bridge health prediction is an essential underpinning science to bridge maintenance optimization, since the effectiveness of optimal maintenance decision is largely dependent on the forecasting accuracy of bridge health performance. The current approaches for bridge health prediction can be categorised into two groups: condition ratings based and structural reliability based. A comprehensive literature review has revealed the following limitations of the current modelling approaches: (1) it is not evident in literature to date that any integrated approaches exist for modelling both serviceability and safety aspects so that both performance criteria can be evaluated coherently; (2) complex system modelling approaches have not been successfully applied to bridge deterioration modelling though a bridge is a complex system composed of many inter-related bridge elements; (3) multiple bridge deterioration factors, such as deterioration dependencies among different bridge elements, observed information, maintenance actions and environmental effects have not been considered jointly; (4) the existing approaches are lacking in Bayesian updating ability to incorporate a variety of event information; (5) the assumption of series and/or parallel relationship for bridge level reliability is always held in all structural reliability estimation of bridge systems. To address the deficiencies listed above, this research proposes three novel models based on the Dynamic Object Oriented Bayesian Networks (DOOBNs) approach. Model I aims to address bridge deterioration in serviceability using condition ratings as the health index. The bridge deterioration is represented in a hierarchical relationship, in accordance with the physical structure, so that the contribution of each bridge element to bridge deterioration can be tracked. A discrete-time Markov process is employed to model deterioration of bridge elements over time. In Model II, bridge deterioration in terms of safety is addressed. The structural reliability of bridge systems is estimated from bridge elements to the entire bridge. By means of conditional probability tables (CPTs), not only series-parallel relationship but also complex probabilistic relationship in bridge systems can be effectively modelled. The structural reliability of each bridge element is evaluated from its limit state functions, considering the probability distributions of resistance and applied load. Both Models I and II are designed in three steps: modelling consideration, DOOBN development and parameters estimation. Model III integrates Models I and II to address bridge health performance in both serviceability and safety aspects jointly. The modelling of bridge ratings is modified so that every basic modelling unit denotes one physical bridge element. According to the specific materials used, the integration of condition ratings and structural reliability is implemented through critical failure modes. Three case studies have been conducted to validate the proposed models, respectively. Carefully selected data and knowledge from bridge experts, the National Bridge Inventory (NBI) and existing literature were utilised for model validation. In addition, event information was generated using simulation to demonstrate the Bayesian updating ability of the proposed models. The prediction results of condition ratings and structural reliability were presented and interpreted for basic bridge elements and the whole bridge system. The results obtained from Model II were compared with the ones obtained from traditional structural reliability methods. Overall, the prediction results demonstrate the feasibility of the proposed modelling approach for bridge health prediction and underpin the assertion that the three models can be used separately or integrated and are more effective than the current bridge deterioration modelling approaches. The primary contribution of this work is to enhance the knowledge in the field of bridge health prediction, where more comprehensive health performance in both serviceability and safety aspects are addressed jointly. The proposed models, characterised by probabilistic representation of bridge deterioration in hierarchical ways, demonstrated the effectiveness and pledge of DOOBNs approach to bridge health management. Additionally, the proposed models have significant potential for bridge maintenance optimization. Working together with advanced monitoring and inspection techniques, and a comprehensive bridge inventory, the proposed models can be used by bridge practitioners to achieve increased serviceability and safety as well as maintenance cost effectiveness.

A high frequency, low voltage stackable full bridge module for modular multilevel cascade converter (MMCC) research

A new small full bridge module for MMCC research is presented. Each full bridge converter cell is a single small (65 × 30 mm) multilayer PCB with two low voltage high current (22 V, 40 A) integrated half bridge ICs and the necessary isolated control signals and auxiliary power supply (2500 V isolation). All devices are surface mount, minimising cell height (4 mm) and parasitic inductance. Each converter cell can be physically stacked with PCB connectors propagating the control signals and inter-cell power connections. Many cells can be trivially stacked to create a large multilevel converter leg with isolated auxiliary power and control signals. Any of the MMCC family members is then easily formed. With a change in placement of stacking connector, a parallel connection of bridges is also possible. Operation of a nine level parallel full bridge is demonstrated at 12 V and 384 kHz switching frequency delivering a 30 W 2 kHz sinewave into a resistive load. A number of new applications for this novel module aside from MMCC development are listed.

Structural identification of a laboratory-based steel through truss cantilevered bridge with suspended span using a layered genetic algorithm with patternsearch step (GAPS)

Structural identification (St-Id) can be considered as the process of updating a finite element (FE) model of a structural system to match the measured response of the structure. This paper presents the St-Id of a laboratory-based steel through-truss cantilevered bridge with suspended span. There are a total of 600 degrees of freedom (DOFs) in the superstructure plus additional DOFs in the substructure. The St-Id of the bridge model used the modal parameters from a preliminary modal test in the objective function of a global optimisation technique using a layered genetic algorithm with patternsearch step (GAPS). Each layer of the St-Id process involved grouping of the structural parameters into a number of updating parameters and running parallel optimisations. The number of updating parameters was increased at each layer of the process. In order to accelerate the optimisation and ensure improved diversity within the population, a patternsearch step was applied to the fittest individuals at the end of each generation of the GA. The GAPS process was able to replicate the mode shapes for the first two lateral sway modes and the first vertical bending mode to a high degree of accuracy and, to a lesser degree, the mode shape of the first lateral bending mode. The mode shape and frequency of the torsional mode did not match very well. The frequencies of the first lateral bending mode, the first longitudinal mode and the first vertical mode matched very well. The frequency of the first sway mode was lower and that of the second sway mode was higher than the true values, indicating a possible problem with the FE model. Improvements to the model and the St-Id process will be presented at the upcoming conference and compared to the results presented in this paper. These improvements will include the use of multiple FE models in a multi-layered, multi-solution, GAPS St-Id approach.

Cyclic Peptide Disulfides - Solution And Solid-State Conformation Of Boc-Cys-Pro-Aib-Cys-S-S-Bridge-Nhme,A Disulfide-Bridged Peptide Helix

The solution and solid-state conformations of the peptide disulfide Boc-Cys-Pro-Aib-Cys-NHMe have been determined by NMR spectroscopy and X-ray diffraction. The Cys(4) and methylamide NH groups are solvent shielded in CDCI3 and (CD,),SO, suggesting their involvement in intramolecular hydrogen bonding. On the basis of known stereochemical preferences of Pro and Aib residues, a consecutive @-turn structure is favored in solution. X-ray diffraction analysis reveals a highly folded 310 helical conformation for the peptide, with the S-S bridge lying approximately parallel to the helix axis, linking residues 1 and 4. The backbone conformational angles are Cys(1) 4 = -121.1', $ = 65.6"; Pro(2) 4 = -58.9', 4 = -34.0'; Aib(3) 4 = -61.8', $ = -17.9'; Cys(4) 4 = -70.5', $ = -18.6'. Two intramolecular hydrogen bonds are observed between Cys(1) CO--HN Cys(4) and Pro(2) CO--HNMe. The disulfide bond has a right-handed chirality, with a dihedral angle (xss) of 82'.

Conductive junctions with parallel graphene sheets.

The establishment of conductive graphene-molecule-graphene junction is investigated through first-principles electronic structure calculations and quantum transport calculations. The junction consists of a conjugated molecule connecting two parallel graphene sheets. The effects of molecular electronic states, structure relaxation, and molecule-graphene contact on the conductance of the junction are explored. A conductance as large as 0.38 conductance quantum is found achievable with an appropriately oriented dithiophene bridge. This work elucidates the designing principles of promising nanoelectronic devices based on conductive graphene-molecule-graphene junctions.

The agonism and synergistic potentiation of weak partial agonists by triethylamine in alpha(1)-adrenergic receptor activation: Evidence for a salt bridge as the initiating process

alpha(1)-adrenergic receptor (AR) activation is thought to be initiated by disruption of a constraining interhelical salt bridge (Porter et al., 1996). Disruption of this salt bridge is achieved through a competition for the aspartic acid residue in transmembrane domain three by the protonated amine of the endogenous ligand norepinephrine and a lysine residue in transmembrane domain seven. To further test this hypothesis, we investigated the possibility that a simple amine could mimic an important functional group of the endogenous ligand and break this alpha(1)-AR ionic constraint leading to agonism. Triethylamine (TEA) was able to generate concentration-dependent increases of soluble inositol phosphates in COS-1 cells transiently transfected with the hamster alpha(1b)-AR and in Rat-1 fibroblasts stably transfected with the human alpha(1a)-AR subtype. TEA was also able to synergistically potentiate the second messenger production by weak partial alpha(1)-AR agonists and this effect was fully inhibited by the alpha(1)-AR antagonist prazosin. However, this synergistic potentiation was not observed for full alpha(1)-AR agonists. Instead, TEA caused a parallel rightward shift of the dose-response curve, consistent with the properties of competitive antagonism. TEA specifically bound to a single population of alpha(1)-ARs with a K-i of 28.7 +/- 4.7 mM. In addition, the site of binding by TEA to the alpha(1)-AR is at the conserved aspartic acid residue in transmembrane domain three, which is part of the constraining salt bridge. These results indicate a direct interaction of TEA in the receptor agonist binding pocket that leads to a disruption of the constraining salt bridge, thereby initiating alpha(1)-AR activation.

Design of highly parallel architecture with Alpha and Handel

We propose a bridge between two important parallel programming paradigms: data parallelism and communicating sequential processes (CSP). Data parallel pipelined architectures obtained with the Alpha language can be embedded in a control intensive application expressed in CSP-based Handel formalism. The interface is formally defined from the semantics of the languages Alpha and Handel. This work will ease the design of compute intensive applications on FPGAs.

Damage analysis of bridge structures using vibrational techniques

Much research is currently centred on the detection of damage in structures using vibrational data. The work presented here examined several areas of interest in support of a practical technique for identifying and locating damage within bridge structures using apparent changes in their vibrational response to known excitation. The proposed goals of such a technique included the need for the measurement system to be operated on site by a minimum number of staff and that the procedure should be as non-invasive to the bridge traffic-flow as possible. Initially the research investigated changes in the vibrational bending characteristics of two series of large-scale model bridge-beams in the laboratory and these included ordinary-reinforced and post-tensioned, prestressed designs. Each beam was progressively damaged at predetermined positions and its vibrational response to impact excitation was analysed. For the load-regime utilised the results suggested that the infuced damage manifested itself as a function of the span of a beam rather than a localised area. A power-law relating apparent damage with the applied loading and prestress levels was then proposed, together with a qualitative vibrational measure of structural damage. In parallel with the laboratory experiments a series of tests were undertaken at the sites of a number of highway bridges. The bridges selected had differing types of construction and geometric design including composite-concrete, concrete slab-and-beam, concrete-slab with supporting steel-troughing constructions together with regular-rectangular, skewed and heavily-skewed geometries. Initial investigations were made of the feasibility and reliability of various methods of structure excitation including traffic and impulse methods. It was found that localised impact using a sledge-hammer was ideal for the purposes of this work and that a cartridge `bolt-gun' could be used in some specific cases.

Parallel Problem Solving from Nature – PPSN XIV:14th International Conference, Edinburgh, UK, September 17-21, 2016, Proceedings

This book constitutes the refereed proceedings of the 14th International Conference on Parallel Problem Solving from Nature, PPSN 2016, held in Edinburgh, UK, in September 2016. The total of 93 revised full papers were carefully reviewed and selected from 224 submissions. The meeting began with four workshops which offered an ideal opportunity to explore specific topics in intelligent transportation Workshop, landscape-aware heuristic search, natural computing in scheduling and timetabling, and advances in multi-modal optimization. PPSN XIV also included sixteen free tutorials to give us all the opportunity to learn about new aspects: gray box optimization in theory; theory of evolutionary computation; graph-based and cartesian genetic programming; theory of parallel evolutionary algorithms; promoting diversity in evolutionary optimization: why and how; evolutionary multi-objective optimization; intelligent systems for smart cities; advances on multi-modal optimization; evolutionary computation in cryptography; evolutionary robotics - a practical guide to experiment with real hardware; evolutionary algorithms and hyper-heuristics; a bridge between optimization over manifolds and evolutionary computation; implementing evolutionary algorithms in the cloud; the attainment function approach to performance evaluation in EMO; runtime analysis of evolutionary algorithms: basic introduction; meta-model assisted (evolutionary) optimization. The papers are organized in topical sections on adaption, self-adaption and parameter tuning; differential evolution and swarm intelligence; dynamic, uncertain and constrained environments; genetic programming; multi-objective, many-objective and multi-level optimization; parallel algorithms and hardware issues; real-word applications and modeling; theory; diversity and landscape analysis.