889 resultados para Radial basis function network
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RTKs-mediated signaling systems and the pathways with which they interact (e.g., those initiated by G protein-mediated signaling) involve a highly cooperative network that sense a large number of cellular inputs and then integrate, amplify, and process this information to orchestrate an appropriate set of cellular responses. The responses include virtually all aspects of cell function, from the most fundamental (proliferation, differentiation) to the most specialized (movement, metabolism, chemosensation). The basic tenets of RTK signaling system seem rather well established. Yet, new pathways and even new molecular players continue to be discovered. Although we believe that many of the essential modules of RTK signaling system are rather well understood, we have relatively little knowledge of the extent of interaction among these modules and their overall quantitative importance.
My research has encompassed the study of both positive and negative signaling by RTKs in C. elegans. I identified the C. elegans S0S-1 gene and showed that it is necessary for multiple RAS-mediated developmental signals. In addition, I demonstrated that there is a SOS-1-independent signaling during RAS-mediated vulval differentiation. By assessing signal outputs from various triple mutants, I have concluded that this SOS-1-independent signaling is not mediated by PTP-2/SHP-2 or the removal of inhibition by GAP-1/ RasGAP and it is not under regulation by SLI-1/Cb1. I speculate that there is either another exchange factor for RASor an as yet unidentified signaling pathway operating during RAS-mediated vulval induction in C. elegans.
In an attempt to uncover the molecular mechanisms of negative regulation of EGFR signaling by SLI-1/Cb1, I and two other colleagues codiscovered that RING finger domain of SLI-1 is partially dispensable for activity. This structure-function analysis shows that there is an ubiquitin protein ligase-independent activity for SLI-1 in regulating EGFR signaling. Further, we identified an inhibitory tyrosine of LET-23/ EGFR requiring sli-1(+)for its effects: removal of this tyrosine closely mimics loss of sli-1 but not loss of other negative regulator function.
By comparative analysis of two RTK pathways with similar signaling mechanisms, I have found that clr-1, a previously identified negative regulator of egl-15 mediated FGFR signaling, is also involved in let-23 EGFR signaling. The success of this approach promises a similar reciprocal test and could potentially extend to the study of other signaling pathways with similar signaling logic.
Finally, by correlating the developmental expression of lin-3 EGF to let-23 EGFR signaling activity, I demonstrated the existence of reciprocal EGF signaling in coordinating the morphogenesis of epithelia. This developmental logic of EGF signaling could provide a basis to understand a universal mechanism for organogenesis.
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A neural network is a highly interconnected set of simple processors. The many connections allow information to travel rapidly through the network, and due to their simplicity, many processors in one network are feasible. Together these properties imply that we can build efficient massively parallel machines using neural networks. The primary problem is how do we specify the interconnections in a neural network. The various approaches developed so far such as outer product, learning algorithm, or energy function suffer from the following deficiencies: long training/ specification times; not guaranteed to work on all inputs; requires full connectivity.
Alternatively we discuss methods of using the topology and constraints of the problems themselves to design the topology and connections of the neural solution. We define several useful circuits-generalizations of the Winner-Take-All circuitthat allows us to incorporate constraints using feedback in a controlled manner. These circuits are proven to be stable, and to only converge on valid states. We use the Hopfield electronic model since this is close to an actual implementation. We also discuss methods for incorporating these circuits into larger systems, neural and nonneural. By exploiting regularities in our definition, we can construct efficient networks. To demonstrate the methods, we look to three problems from communications. We first discuss two applications to problems from circuit switching; finding routes in large multistage switches, and the call rearrangement problem. These show both, how we can use many neurons to build massively parallel machines, and how the Winner-Take-All circuits can simplify our designs.
Next we develop a solution to the contention arbitration problem of high-speed packet switches. We define a useful class of switching networks and then design a neural network to solve the contention arbitration problem for this class. Various aspects of the neural network/switch system are analyzed to measure the queueing performance of this method. Using the basic design, a feasible architecture for a large (1024-input) ATM packet switch is presented. Using the massive parallelism of neural networks, we can consider algorithms that were previously computationally unattainable. These now viable algorithms lead us to new perspectives on switch design.
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Questões climáticas, atmosféricas e de poluição ambiental têm tornado o uso final da energia assunto de interesse mundial. Sistemas com tração elétrica oferecem a oportunidade de redução de emissões. O mix de energia caracterizado pela matriz energética brasileira viabiliza o desenvolvimento desta tecnologia. É desenvolvida aqui uma metodologia para conversão de veículos equipados com motores a combustão interna para tração elétrica. A metodologia considera fatores como o peso e tamanho, o torque de partida, transmissão e potência, entre outros. Ferramentas matemáticas e a prática corrente fornecem a base para a elaboração deste trabalho, que descreve a análise de desempenho de veículos elétricos, os componentes utilizados, as equações mecânicas e os critérios para escolha do veículo ideal para conversão. É apresentada a execução de um projeto de conversão de uma Kombi para tração elétrica, cujo objetivo tem caráter educativo, buscando assim promover os benefícios da tecnologia veicular elétrica. Para viabilização do experimento, o trabalho conclui que é necessário ampliar a demanda por nacionalização de tecnologia, o que tornaria o projeto uma realidade comercialmente viável. Além disto, há necessidade de políticas públicas para o incentivo da tecnologia veicular elétrica no Brasil. Este trabalho apresenta uma contribuição para converter veículos para tração elétrica, visto que sistematiza as etapas de projeto, a partir das quais outros poderão seguir, utilizando componentes encontrados no mercado nacional.
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The current power grid is on the cusp of modernization due to the emergence of distributed generation and controllable loads, as well as renewable energy. On one hand, distributed and renewable generation is volatile and difficult to dispatch. On the other hand, controllable loads provide significant potential for compensating for the uncertainties. In a future grid where there are thousands or millions of controllable loads and a large portion of the generation comes from volatile sources like wind and solar, distributed control that shifts or reduces the power consumption of electric loads in a reliable and economic way would be highly valuable.
Load control needs to be conducted with network awareness. Otherwise, voltage violations and overloading of circuit devices are likely. To model these effects, network power flows and voltages have to be considered explicitly. However, the physical laws that determine power flows and voltages are nonlinear. Furthermore, while distributed generation and controllable loads are mostly located in distribution networks that are multiphase and radial, most of the power flow studies focus on single-phase networks.
This thesis focuses on distributed load control in multiphase radial distribution networks. In particular, we first study distributed load control without considering network constraints, and then consider network-aware distributed load control.
Distributed implementation of load control is the main challenge if network constraints can be ignored. In this case, we first ignore the uncertainties in renewable generation and load arrivals, and propose a distributed load control algorithm, Algorithm 1, that optimally schedules the deferrable loads to shape the net electricity demand. Deferrable loads refer to loads whose total energy consumption is fixed, but energy usage can be shifted over time in response to network conditions. Algorithm 1 is a distributed gradient decent algorithm, and empirically converges to optimal deferrable load schedules within 15 iterations.
We then extend Algorithm 1 to a real-time setup where deferrable loads arrive over time, and only imprecise predictions about future renewable generation and load are available at the time of decision making. The real-time algorithm Algorithm 2 is based on model-predictive control: Algorithm 2 uses updated predictions on renewable generation as the true values, and computes a pseudo load to simulate future deferrable load. The pseudo load consumes 0 power at the current time step, and its total energy consumption equals the expectation of future deferrable load total energy request.
Network constraints, e.g., transformer loading constraints and voltage regulation constraints, bring significant challenge to the load control problem since power flows and voltages are governed by nonlinear physical laws. Remarkably, distribution networks are usually multiphase and radial. Two approaches are explored to overcome this challenge: one based on convex relaxation and the other that seeks a locally optimal load schedule.
To explore the convex relaxation approach, a novel but equivalent power flow model, the branch flow model, is developed, and a semidefinite programming relaxation, called BFM-SDP, is obtained using the branch flow model. BFM-SDP is mathematically equivalent to a standard convex relaxation proposed in the literature, but numerically is much more stable. Empirical studies show that BFM-SDP is numerically exact for the IEEE 13-, 34-, 37-, 123-bus networks and a real-world 2065-bus network, while the standard convex relaxation is numerically exact for only two of these networks.
Theoretical guarantees on the exactness of convex relaxations are provided for two types of networks: single-phase radial alternative-current (AC) networks, and single-phase mesh direct-current (DC) networks. In particular, for single-phase radial AC networks, we prove that a second-order cone program (SOCP) relaxation is exact if voltage upper bounds are not binding; we also modify the optimal load control problem so that its SOCP relaxation is always exact. For single-phase mesh DC networks, we prove that an SOCP relaxation is exact if 1) voltage upper bounds are not binding, or 2) voltage upper bounds are uniform and power injection lower bounds are strictly negative; we also modify the optimal load control problem so that its SOCP relaxation is always exact.
To seek a locally optimal load schedule, a distributed gradient-decent algorithm, Algorithm 9, is proposed. The suboptimality gap of the algorithm is rigorously characterized and close to 0 for practical networks. Furthermore, unlike the convex relaxation approach, Algorithm 9 ensures a feasible solution. The gradients used in Algorithm 9 are estimated based on a linear approximation of the power flow, which is derived with the following assumptions: 1) line losses are negligible; and 2) voltages are reasonably balanced. Both assumptions are satisfied in practical distribution networks. Empirical results show that Algorithm 9 obtains 70+ times speed up over the convex relaxation approach, at the cost of a suboptimality within numerical precision.
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This dissertation primarily describes chemical-scale studies of nicotinic acetylcholine receptors (nAChRs) in order to better understand ligand-receptor selectivity and allosteric modulation influences during receptor activation. Electrophysiology coupled with canonical and non-canonical amino acids mutagenesis is used to probe subtle changes in receptor function.
The first half of this dissertation focuses on differential agonist selectivity of α4β2-containing nAChRs. The α4β2 nAChR can assemble in alternative stoichiometries as well as assemble with other accessory subunits. Chapter 2 identifies key structural residues that dictate binding and activation of three stoichiometry-dependent α4β2 receptor ligands: sazetidine-A, cytisine, and NS9283. These do not follow previously suggested hydrogen-bonding patterns of selectivity. Instead, three residues on the complementary subunit strongly influence binding ability of a ligand and receptor activation. Chapter 3 involves isolation of a α5α4β2 receptor-enriched population to test for a potential alternative agonist binding location at the α5 α4 interface. Results strongly suggest that agonist occupation of this site is not necessary for receptor activation and that the α5 subunit only incorporates at the accessory subunit location.
The second half of this dissertation seeks to identify residue interactions with positive allosteric modulators (PAMs) of the α7 nAChR. Chapter 4 focuses on methods development to study loss of potentiation of Type I PAMs, which indicate residues vital to propagation of PAM effects and/or binding. Chapter 5 investigates α7 receptor modulation by a Type II PAM (PNU 120596). These results show that PNU 120596 does not alter the agonist binding site, thus is relegated to influencing only the gating component of activation. From this, we were able to map a potential network of residues from the agonist binding site to the proposed PNU 120596 binding site that are essential for receptor potentiation.
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A grating-lens combination unit is developed to form a scaling self-transform function that can self-image on scale. Then an array of many such grating-lens units is used for the optical interconnection of a two-dimensional neural network, and experiments are carried out. We find that our idea is feasible, the optical interconnection system is simple, and optical adjustment is easy. (C) 1998 Optical Society of America.
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Acetyltransferases and deacetylases catalyze the addition and removal, respectively, of acetyl groups to the epsilon-amino group of protein lysine residues. This modification can affect the function of a protein through several means, including the recruitment of specific binding partners called acetyl-lysine readers. Acetyltransferases, deacetylases, and acetyl-lysine readers have emerged as crucial regulators of biological processes and prominent targets for the treatment of human disease. This work describes a combination of structural, biochemical, biophysical, cell-biological, and organismal studies undertaken on a set of proteins that cumulatively include all steps of the acetylation process: the acetyltransferase MEC-17, the deacetylase SIRT1, and the acetyl-lysine reader DPF2. Tubulin acetylation by MEC-17 is associated with stable, long-lived microtubule structures. We determined the crystal structure of the catalytic domain of human MEC-17 in complex with the cofactor acetyl-CoA. The structure in combination with an extensive enzymatic analysis of MEC-17 mutants identified residues for cofactor and substrate recognition and activity. A large, evolutionarily conserved hydrophobic surface patch distal to the active site was shown to be necessary for catalysis, suggesting that specificity is achieved by interactions with the alpha-tubulin substrate that extend outside of the modified surface loop. Experiments in C. elegans showed that while MEC-17 is required for touch sensitivity, MEC-17 enzymatic activity is dispensible for this behavior. SIRT1 deacetylates a wide range of substrates, including p53, NF-kappaB, FOXO transcription factors, and PGC-1-alpha, with roles in cellular processes ranging from energy metabolism to cell survival. SIRT1 activity is uniquely controlled by a C-terminal regulatory segment (CTR). Here we present crystal structures of the catalytic domain of human SIRT1 in complex with the CTR in an apo form and in complex with a cofactor and a pseudo-substrate peptide. The catalytic domain adopts the canonical sirtuin fold. The CTR forms a beta-hairpin structure that complements the beta-sheet of the NAD^+-binding domain, covering an essentially invariant, hydrophobic surface. A comparison of the apo and cofactor bound structures revealed conformational changes throughout catalysis, including a rotation of a smaller subdomain with respect to the larger NAD^+-binding subdomain. A biochemical analysis identified key residues in the active site, an inhibitory role for the CTR, and distinct structural features of the CTR that mediate binding and inhibition of the SIRT1 catalytic domain. DPF2 represses myeloid differentiation in acute myelogenous leukemia. Finally, we solved the crystal structure of the tandem PHD domain of human DPF2. We showed that DPF2 preferentially binds H3 tail peptides acetylated at Lys14, and binds H4 tail peptides with no preference for acetylation state. Through a structural and mutational analysis we identify the molecular basis of histone recognition. We propose a model for the role of DPF2 in AML and identify the DPF2 tandem PHD finger domain as a promising novel target for anti-leukemia therapeutics.
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Part I
The latent heat of vaporization of n-decane is measured calorimetrically at temperatures between 160° and 340°F. The internal energy change upon vaporization, and the specific volume of the vapor at its dew point are calculated from these data and are included in this work. The measurements are in excellent agreement with available data at 77° and also at 345°F, and are presented in graphical and tabular form.
Part II
Simultaneous material and energy transport from a one-inch adiabatic porous cylinder is studied as a function of free stream Reynolds Number and turbulence level. Experimental data is presented for Reynolds Numbers between 1600 and 15,000 based on the cylinder diameter, and for apparent turbulence levels between 1.3 and 25.0 per cent. n-heptane and n-octane are the evaporating fluids used in this investigation.
Gross Sherwood Numbers are calculated from the data and are in substantial agreement with existing correlations of the results of other workers. The Sherwood Numbers, characterizing mass transfer rates, increase approximately as the 0.55 power of the Reynolds Number. At a free stream Reynolds Number of 3700 the Sherwood Number showed a 40% increase as the apparent turbulence level of the free stream was raised from 1.3 to 25 per cent.
Within the uncertainties involved in the diffusion coefficients used for n-heptane and n-octane, the Sherwood Numbers are comparable for both materials. A dimensionless Frössling Number is computed which characterizes either heat or mass transfer rates for cylinders on a comparable basis. The calculated Frössling Numbers based on mass transfer measurements are in substantial agreement with Frössling Numbers calculated from the data of other workers in heat transfer.
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Hair cells from the bull frog's sacculus, a vestibular organ responding to substrate-borne vibration, possess electrically resonant membrane properties which maximize the sensitivity of each cell to a particular frequency of mechanical input. The electrical resonance of these cells and its underlying ionic basis were studied by applying gigohm-seal recording techniques to solitary hair cells enzymatically dissociated from the sacculus. The contribution of electrical resonance to frequency selectivity was assessed from microelectrode recordings from hair cells in an excised preparation of the sacculus.
Electrical resonance in the hair cell is demonstrated by damped membrane-potential oscillations in response to extrinsic current pulses applied through the recording pipette. This response is analyzed as that of a damped harmonic oscillator. Oscillation frequency rises with membrane depolarization, from 80-160 Hz at resting potential to asymptotic values of 200-250 Hz. The sharpness of electrical tuning, denoted by the electrical quality factor, Qe, is a bell-shaped function of membrane voltage, reaching a maximum value around eight at a membrane potential slightly positive to the resting potential.
In whole cells, three time-variant ionic currents are activated at voltages more positive than -60 to -50 mV; these are identified as a voltage-dependent, non-inactivating Ca current (Ica), a voltage-dependent, transient K current (Ia), and a Ca-dependent K current (Ic). The C channel is identified in excised, inside-out membrane patches on the basis of its large conductance (130-200 pS), its selective permeability to Kover Na or Cl, and its activation by internal Ca ions and membrane depolarization. Analysis of open- and closed-lifetime distributions suggests that the C channel can assume at least two open and three closed kinetic states.
Exposing hair cells to external solutions that inhibit the Ca or C conductances degrades the electrical resonance properties measured under current-clamp conditions, while blocking the A conductance has no significant effect, providing evidence that only the Ca and C conductances participate in the resonance mechanism. To test the sufficiency of these two conductances to account for electrical resonance, a mathematical model is developed that describes Ica, Ic, and intracellular Ca concentration during voltage-clamp steps. Ica activation is approximated by a third-order Hodgkin-Huxley kinetic scheme. Ca entering the cell is assumed to be confined to a small submembrane compartment which contains an excess of Ca buffer; Ca leaves this space with first-order kinetics. The Ca- and voltage-dependent activation of C channels is described by a five-state kinetic scheme suggested by the results of single-channel observations. Parameter values in the model are adjusted to fit the waveforms of Ica and Ic evoked by a series of voltage-clamp steps in a single cell. Having been thus constrained, the model correctly predicts the character of voltage oscillations produced by current-clamp steps, including the dependencies of oscillation frequency and Qe on membrane voltage. The model shows quantitatively how the Ca and C conductances interact, via changes in intracellular Ca concentration, to produce electrical resonance in a vertebrate hair cell.
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On the basis of the space-time Wigner distribution function (STWDF), we use the matrix formalism to study the propagation laws for the intensity moments of quasi-monochromatic and polychromatic pulsed paraxial beams. The advantages of this approach are reviewed. Also, a least-squares fitting method for interpreting the physical meaning of the effective curvature matrix is described by means of the STWDF. Then the concept is extended to the higher-order situation, and what me believe is a novel technique for characterizing the beam phase is presented. (C) 1999 Optical Society of America [S0740-3232(99)001009-1].
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Nos dias de hoje, podemos constatar o crescimento das formas de linguagem mediadas pelas tecnologias da informação e comunicação. É em torno dessa constatação e nesse contexto que esta dissertação se insere. Seu tema é a caracterização do par post/comentário à luz da noção de gêneros textuais. Nosso objetivo é refletir sobre o referido, a fim de responder os seguintes questionamentos: (a) se post e comentário são dois gêneros textuais ou partes de um mesmo fenômeno de comunicação/gênero; (b) se são gêneros, como caracterizá-los e diferenciá-los; (c) não sendo o post um novo gênero textual, que especificidades podem caracterizá-lo como ferramenta e quais os aspectos que o vinculam ao gênero comentário. A fim de respondê-los, nossa opção metodológica foi por um estudo documental de cunho qualitativo. Este consistiu na coleta de publicações feitas no perfil da pesquisadora na rede social Facebook por diferentes sujeitos, no período pré e pós eleições brasileiras de 2014, especificamente no mês de outubro. Os posts e comentários selecionados referem-se exclusivamente à temática das eleições presidenciais. Entendemos que as redes sociais têm sido grandes incentivadoras à produção escrita e, consequentemente, promotoras de atividades de compreensão leitora. E, no que concerne em particular ao tema escolhido, acolheram e fomentaram intensos debates. As reflexões sobre leitura, portanto, perpassam este trabalho porque, ao pensarmos no nascimento e uso de um gênero, pensamos, também, em sua recepção, logo, nos processos leitores envolvidos. Para analisar os dados, utilizamos a proposta de Donato (2014), discutindo os quatro pilares constituintes do gênero função comunicativa, forma, conteúdo e suporte, e também pensando em três níveis: o da produção, recepção e contextualização. Como base teórico-metodológica seguimos a perspectiva da sociocognição, calcada especialmente nos estudos de Marcuschi (2005, 2008, 2010), Koch (1996, 2003) e Koch e Elias (2008, 2013), assim como fundamentos de Bakhtin (1997) sobre o caráter sócio-histórico dos gêneros. A título de conclusão, segundo nossas análises, salientamos a interdependência dos elementos do par estudado. No entanto, defendemos a delimitação do post enquanto gênero textual eminentemente digital e não apenas uma ferramenta ou parte do gênero comentário
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The measured toughness J(C) of adipose and dermal porcine tissues are 4.1 and 17 kJ m(-2), respectively, via a trouser tear test. An assessment is made of the contribution to overall toughness from the microstructural elements. The analysis suggests that the toughness of adipose tissue is determined by the collagen network that surrounds the adipocytes. The volume fraction of the interlobular septa is sufficiently low for it to make a negligible contribution to the macroscopic toughness.
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An analysis of the factor-product relationship in the semi-intensive shrimp farming system of Kerala, farm basis and hectare basis, we are attempted and the results reported in this paper. The Cobb-Douglas model, in which the physical relationship between input and output is estimated, and the marginal analysis then employed to evaluate the producer behaviour, was used for the analysis. The study was based on empirical data collected during November 1994 to May 1996, covering three seasons, from 21 farms spread over Alappuzha, Ernakulam and Kasaragod districts of the state. The sample covered a total area of 61.06 ha. Of the 11 explanatory variables considered in the model, the size of the farm, casual labour and chemical fertilizers were found statistically significant. It was also observed that the factors such as age of pond, experience of the farmer, feed, miscellaneous costs, number of seed stocked and skilled labour contributed positively to the output. The estimated industry production function exhibited unitary economies of scale. The estimated mean output was 3937 kg/ha. The test of multi-co-linearity showed that there is no problem of dominant variable. On the basis of the marginal product and the given input-output prices, the optimum amounts of seed, feed and casual labour were estimated. They were about 97139 seed, 959 kg of feed and 585 man-days of casual labour per farm. This indicated the need for reducing the stocking density and amount of feed from the present levels, in order to maximise profit. Based on the finding of the study, suggestions for improving the industry production function are proposed.
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Purpose - The purpose of this paper is to explore the impact of configuration on supply network capability. It was believed that a configuration perspective might provide new insights on the capability and performance of supply networks, a gap in the literature, and provide a basis for the development of tools to aid their analysis and design. Design/methodology/ approach - The methodology involved the development of a configuration definition and mapping approach extending established strategic and firm level constructs to the network operational level. The resulting tools were tested and refined in a series of case studies across a range of sectors and value chain models. Supply network capability assessments, from the perspective of the focal firm, were then compared with their configuration profiles. Findings - The configuration mapping tools were found to give new insights into the structure of supply networks and allow comparisons to be made across sectors and business models through the use of consistent and quantitative methods and common presentation. They provide the foundations for linking configuration to capability and performance, and contribute to supply network design and development by highlighting the intrinsic capabilities associated with different configurations. Research limitations/implications - Although multiple case networks have been investigated, the configuration exemplars remain suggestive models. The research suggests that a re-evaluation of operational process excellence models is needed, where the link between process maturity and performance may require a configuration context. Practical implications - Advantages of particular configurations have been identified with implications for supply network development and industrial policy. Originality/value - The paper seeks to develop established strategic management configuration concepts to the analysis and design of supply networks by providing a robust operational definition of supply network configuration and novel tools for their mapping and assessment. © Emerald Group Publishing Limited.
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It is essential to monitor deteriorated civil engineering structures cautiously to detect symptoms of their serious disruptions. A wireless sensor network can be an effective system for monitoring civil engineering structures. It is fast to deploy sensors especially in difficult-to-access areas, and it is extendable without any cable extensions. Since our target is to monitor deteriorations of civil engineering structures such as cracks at tunnel linings, most of the locations of sensors are known, and sensors are not required to move dynamically. Therefore, we focus on developing a deployment plan of a static network in order to reduce the value of a cost function such as initial installation cost and summation of communication distances of the network. The key issue of the deployment is the location of relays that forward sensing data from sensors to a data collection device called a gateway. In this paper, we propose a relay deployment-planning tool that can be used to design a wireless sensor network for monitoring civil engineering structures. For the planning tool, we formalize the model and implement a local search based algorithm to find a quasi-optimal solution. Our solution guarantees two routings from a sensor to a gateway, which can provide higher reliability of the network. We also show the application of our experimental tool to the actual environment in the London Underground.