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Sample records for optimizing dvl pdz

  1. Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches

    Science.gov (United States)

    Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

    2018-05-01

    The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

  2. Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches.

    Science.gov (United States)

    Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

    2018-04-07

    The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

  3. Inertial Navigation System/Doppler Velocity Log (INS/DVL Fusion with Partial DVL Measurements

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    Asaf Tal

    2017-02-01

    Full Text Available The Technion autonomous underwater vehicle (TAUV is an ongoing project aiming to develop and produce a small AUV to carry on research missions, including payload dropping, and to demonstrate acoustic communication. Its navigation system is based on an inertial navigation system (INS aided by a Doppler velocity log (DVL, magnetometer, and pressure sensor (PS. In many INSs, such as the one used in TAUV, only the velocity vector (provided by the DVL can be used for aiding the INS, i.e., enabling only a loosely coupled integration approach. In cases of partial DVL measurements, such as failure to maintain bottom lock, the DVL cannot estimate the vehicle velocity. Thus, in partial DVL situations no velocity data can be integrated into the TAUV INS, and as a result its navigation solution will drift in time. To circumvent that problem, we propose a DVL-based vehicle velocity solution using the measured partial raw data of the DVL and additional information, thereby deriving an extended loosely coupled (ELC approach. The implementation of the ELC approach requires only software modification. In addition, we present the TAUV six degrees of freedom (6DOF simulation that includes all functional subsystems. Using this simulation, the proposed approach is evaluated and the benefit of using it is shown.

  4. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  5. Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cong, E-mail: wangcongweihai@126.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Dai, Jinghong, E-mail: daijinghongnew@163.com [Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University (China); Sun, Zhaorui, E-mail: lanseyunduan@163.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Department of Emergency, Jinling Hospital, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Shi, Chaowen, E-mail: willscw@live.cn [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Cao, Honghui, E-mail: caohonghui92@gmail.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); and others

    2015-02-01

    In this study, we determined the effects of transforming growth factor-beta (TGF-β) and Wnt/β-catenin signaling on myofibroblast differentiation of NIH/3T3 fibroblasts in vitro and evaluated the therapeutic efficacy of NSC668036 in bleomycin-induced pulmonary fibrosis murine model. In vitro study, NSC668036, a small organic inhibitor of the PDZ domain in Dvl, suppressed β-catenin-driven gene transcription and abolished TGF-β1-induced migration, expression of collagen I and α-smooth muscle actin (α-SMA) in fibroblasts. In vivo study, we found that NSC668036 significantly suppressed accumulation of collagen I, α-SMA, and TGF-β1 but increased the expression of CK19, Occludin and E-cadherin that can inhibit pulmonary fibrogenesis. Because fibrotic lung exhibit aberrant activation of Wnt/β-catenin signaling, these data collectively suggest that inhibition of Wnt/β-catenin signaling at the Dvl level may be an effective approach to the treatment of fibrotic lung diseases. - Highlights: • NSC668036 inhibited the proliferation and migration of NIH/3T3 fibroblasts. • NSC668036 suppressed the Wnt/β-catenin signaling pathway. • TGF-β-induced stimulation of profibrotic responses were inhibited by NSC668036. • NSC668036 can inhibit the development of bleomycin-induced pulmonary fibrosis.

  6. Structure of the first PDZ domain of human PSD-93

    DEFF Research Database (Denmark)

    Fiorentini, Monica; Nielsen, Ann Kallehauge; Kristensen, Ole

    2009-01-01

    The crystal structure of the PDZ1 domain of human PSD-93 has been determined to 2.0 A resolution. The PDZ1 domain forms a crystallographic trimer that is also predicted to be stable in solution. The main contributions to the stabilization of the trimer seem to arise from interactions involving...... the PDZ1-PDZ2 linker region at the extreme C-terminus of PDZ1, implying that the oligomerization that is observed is not of biological significance in full-length PSD-93. Comparison of the structures of the binding cleft of PSD-93 PDZ1 with the previously reported structures of PSD-93 PDZ2 and PDZ3...

  7. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

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    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  8. An IMM-Aided ZUPT Methodology for an INS/DVL Integrated Navigation System.

    Science.gov (United States)

    Yao, Yiqing; Xu, Xiaosu; Xu, Xiang

    2017-09-05

    Inertial navigation system (INS)/Doppler velocity log (DVL) integration is the most common navigation solution for underwater vehicles. Due to the complex underwater environment, the velocity information provided by DVL always contains some errors. To improve navigation accuracy, zero velocity update (ZUPT) technology is considered, which is an effective algorithm for land vehicles to mitigate the navigation error during the pure INS mode. However, in contrast to ground vehicles, the ZUPT solution cannot be used directly for underwater vehicles because of the existence of the water current. In order to leverage the strengths of the ZUPT method and the INS/DVL solution, an interactive multiple model (IMM)-aided ZUPT methodology for the INS/DVL-integrated underwater navigation system is proposed. Both the INS/DVL and INS/ZUPT models are constructed and operated in parallel, with weights calculated according to their innovations and innovation covariance matrices. Simulations are conducted to evaluate the proposed algorithm. The results indicate that the IMM-aided ZUPT solution outperforms both the INS/DVL solution and the INS/ZUPT solution in the underwater environment, which can properly distinguish between the ZUPT and non-ZUPT conditions. In addition, during DVL outage, the effectiveness of the proposed algorithm is also verified.

  9. Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons

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    Čajánek, Lukáš; Ganji, Ranjani Sri; Henriques-Oliveira, Catarina; Theofilopoulos, Spyridon; Koník, Peter

    2013-01-01

    Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway. PMID:23109420

  10. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

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    Rotem Kadir

    2016-03-01

    Full Text Available Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

  11. DVL Velocity Aiding in the HUGIN 1000 Integrated Inertial Navigation System

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    Bjørn Jalving

    2004-10-01

    Full Text Available The RDI WHN-600 Doppler Velocity Log (DVL is a key navigation sensor for the HUG1N 1000 Autonomous Underwater Vehicle (AUV. HUGIN 1000 is designed for autonomous submerged operation for long periods of time. This is facilitated by a low drift velocity aided Inertial Navigation System (INS. Major factors determining the position error growth are the IMU and DVL error characteristics and the mission plan pattern_ For instance, low frequency DVL errors cause an approximately linear drift in a straight-line trajectory, while these errors tend to be cancelled out by a lawn mower pattern_ The paper focuses on the accuracy offered by the DVL. HUGIN 1000 is a permanent organic mine countermeasure (MCM capacity on the Royal Norwegian Navy MCM vessel KNM Karmoy. HUGIN 1000 will be part of the NATO force MCMFORNORTH in fall 2004.

  12. Significant Overexpression of DVL1 in Taiwanese Colorectal Cancer Patients with Liver Metastasis

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    Shiu-Ru Lin

    2013-10-01

    Full Text Available Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs. Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2 in the cancer patients. We used a weighted enzymatic chip array (WEnCA including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I–III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214 of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588–12.837; p < 0.0001 on univariate analysis; OR: 3.768; 95% CI: 1.469–9.665; p = 0.006 on multivariate analysis. IHC staining of the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of CRC cells. High expression of DVL1 was observed in 55% (33/60 of CRC tumor specimens and was associated significantly with tumor depth, perineural invasion and liver metastasis status (all p < 0.05. Our experimental results demonstrated that DVL1 is significantly overexpressed in CRC patients with liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients.

  13. Expression Levels and Localizations of DVL3 and sFRP3 in Glioblastoma

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    Anja Kafka

    2017-01-01

    Full Text Available The expression patterns of critical molecular components of Wnt signaling, sFRP3 and DVL3, were investigated in glioblastoma, the most aggressive form of primary brain tumors, with the aim to offer potential biomarkers. The protein expression levels and localizations in tumor tissue were revealed by immunohistochemistry and evaluated by the semiquantitative method and immunoreactivity score. Majority of glioblastomas had moderate expression levels for both DVL3 (52.4% and sFRP3 (52.3%. Strong expression levels were observed in 23.1% and 36.0% of samples, respectively. DVL3 was localized in cytoplasm in 97% of glioblastomas, of which 44% coexpressed the protein in the nucleus. sFRP3 subcellular distribution showed that it was localized in the cytoplasm in 94% of cases. Colocalization in the cytoplasm and nucleus was observed in 50% of samples. Wilcox test indicated that the domination of the strong signal is in connection with simultaneous localization of DVL3 protein in the cytoplasm and the nucleus. Patients with strong expression of DVL3 will significantly more often have the protein in the nucleus (P=6.33×10−5. No significant correlation between the two proteins was established, nor were their signal strengths correlated with epidemiological parameters. Our study contributes to better understanding of glioblastoma molecular profile.

  14. Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop.

    Science.gov (United States)

    Amacher, Jeanine F; Cushing, Patrick R; Bahl, Christopher D; Beck, Tobias; Madden, Dean R

    2013-02-15

    PDZ (PSD-95/Dlg/ZO-1) binding domains often serve as cellular traffic engineers, controlling the localization and activity of a wide variety of binding partners. As a result, they play important roles in both physiological and pathological processes. However, PDZ binding specificities overlap, allowing multiple PDZ proteins to mediate distinct effects on shared binding partners. For example, several PDZ domains bind the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), an epithelial ion channel mutated in CF. Among these binding partners, the CFTR-associated ligand (CAL) facilitates post-maturational degradation of the channel and is thus a potential therapeutic target. Using iterative optimization, we previously developed a selective CAL inhibitor peptide (iCAL36). Here, we investigate the stereochemical basis of iCAL36 specificity. The crystal structure of iCAL36 in complex with the CAL PDZ domain reveals stereochemical interactions distributed along the peptide-binding cleft, despite the apparent degeneracy of the CAL binding motif. A critical selectivity determinant that distinguishes CAL from other CFTR-binding PDZ domains is the accommodation of an isoleucine residue at the C-terminal position (P(0)), a characteristic shared with the Tax-interacting protein-1. Comparison of the structures of these two PDZ domains in complex with ligands containing P(0) Leu or Ile residues reveals two distinct modes of accommodation for β-branched C-terminal side chains. Access to each mode is controlled by distinct residues in the carboxylate-binding loop. These studies provide new insights into the primary sequence determinants of binding motifs, which in turn control the scope and evolution of PDZ interactomes.

  15. Structure function relations in PDZ-domain-containing proteins ...

    Indian Academy of Sciences (India)

    G P Manjunath

    2017-12-30

    Dec 30, 2017 ... Implications for protein networks in cellular signalling ..... However, surface plasmon resonance .... entiate between conformation changes in the PDZ domain or .... NHERF1, through long-range electrostatic and hydrophobic.

  16. Application of wavelet transform for PDZ domain classification.

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    Khaled Daqrouq

    Full Text Available PDZ domains have been identified as part of an array of signaling proteins that are often unrelated, except for the well-conserved structural PDZ domain they contain. These domains have been linked to many disease processes including common Avian influenza, as well as very rare conditions such as Fraser and Usher syndromes. Historically, based on the interactions and the nature of bonds they form, PDZ domains have most often been classified into one of three classes (class I, class II and others - class III, that is directly dependent on their binding partner. In this study, we report on three unique feature extraction approaches based on the bigram and trigram occurrence and existence rearrangements within the domain's primary amino acid sequences in assisting PDZ domain classification. Wavelet packet transform (WPT and Shannon entropy denoted by wavelet entropy (WE feature extraction methods were proposed. Using 115 unique human and mouse PDZ domains, the existence rearrangement approach yielded a high recognition rate (78.34%, which outperformed our occurrence rearrangements based method. The recognition rate was (81.41% with validation technique. The method reported for PDZ domain classification from primary sequences proved to be an encouraging approach for obtaining consistent classification results. We anticipate that by increasing the database size, we can further improve feature extraction and correct classification.

  17. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1

    DEFF Research Database (Denmark)

    Madsen, Kenneth L; Beuming, Thijs; Niv, Masha Y

    2005-01-01

    PICK1 (protein interacting with C kinase 1) contains a single PDZ domain known to mediate interaction with the C termini of several receptors, transporters, ion channels, and kinases. In contrast to most PDZ domains, the PICK1 PDZ domain interacts with binding sequences classifiable as type I (te...

  18. A Novel Scheme for DVL-Aided SINS In-Motion Alignment Using UKF Techniques

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    Wenqi Wu

    2013-01-01

    Full Text Available In-motion alignment of Strapdown Inertial Navigation Systems (SINS without any geodetic-frame observations is one of the toughest challenges for Autonomous Underwater Vehicles (AUV. This paper presents a novel scheme for Doppler Velocity Log (DVL aided SINS alignment using Unscented Kalman Filter (UKF which allows large initial misalignments. With the proposed mechanism, a nonlinear SINS error model is presented and the measurement model is derived under the assumption that large misalignments may exist. Since a priori knowledge of the measurement noise covariance is of great importance to robustness of the UKF, the covariance-matching methods widely used in the Adaptive KF (AKF are extended for use in Adaptive UKF (AUKF. Experimental results show that the proposed DVL-aided alignment model is effective with any initial heading errors. The performances of the adaptive filtering methods are evaluated with regards to their parameter estimation stability. Furthermore, it is clearly shown that the measurement noise covariance can be estimated reliably by the adaptive UKF methods and hence improve the performance of the alignment.

  19. The Tiam1 PDZ Domain Couples to Syndecan1 and Promotes Cell-Matrix Adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Shepherd, Tyson R; Klaus, Suzi M; Liu, Xu; Ramaswamy, S; DeMali, Kris A; Fuentes, Ernesto J [Iowa

    2010-08-12

    The T-cell lymphoma invasion and metastasis gene 1 (Tiam1) is a guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions. This GEF contains several protein-protein interaction domains, including a PDZ domain. Earlier studies identified a consensus PDZ-binding motif and a synthetic peptide capable of binding to the Tiam1 PDZ domain, but little is known about its ligand specificity and physiological role in cells. Here, we investigated the structure, specificity, and function of the Tiam1 PDZ domain. We determined the crystal structures of the Tiam1 PDZ domain free and in complex with a 'model' peptide, which revealed the structural basis for ligand specificity. Protein database searches using the consensus PDZ-binding motif identified two eukaryotic cell adhesion proteins, Syndecan1 and Caspr4, as potential Tiam1 PDZ domain binding proteins. Equilibrium binding experiments confirmed that C-terminal peptides derived from Syndecan1 and Caspr4 bound the Tiam1 PDZ domain. NMR chemical shift perturbation experiments indicated that the Tiam1 PDZ/Syndecan1 and PDZ/Caspr4 complexes were structurally distinct and identified key residues likely to be responsible for ligand selectivity. Moreover, cell biological analysis established that Syndecan1 is a physiological binding partner of Tiam1 and that the PDZ domain has a function in cell-matrix adhesion and cell migration. Collectively, our data provide insight into the structure, specificity, and function of the Tiam1 PDZ domain. Importantly, our data report on a physiological role for the Tiam1 PDZ domain and establish a novel link between two previously unrelated signal transduction pathways, both of which are implicated in cancer.

  20. Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Marina E.; Fletcher, Georgina C.; O’Reilly, Nicola; Purkiss, Andrew G.; Thompson, Barry J. [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); McDonald, Neil Q., E-mail: neil.mcdonald@cancer.org.uk [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); Birkbeck College, University of London, Malet Street, London WC1E 7HX (United Kingdom)

    2015-03-01

    This study characterizes the interaction between the carboxy-terminal (ERLI) motif of the essential polarity protein Crb and the Pals1/Stardust PDZ-domain protein. Structures of human Pals1 PDZ with and without a Crb peptide are described, explaining the highly conserved nature of the ERLI motif and revealing a sterically blocked peptide-binding groove in the absence of ligand. Many components of epithelial polarity protein complexes possess PDZ domains that are required for protein interaction and recruitment to the apical plasma membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust, MPP5), a member of the p55 family of membrane-associated guanylate kinases (MAGUKs). This study describes the molecular interaction between the Crb carboxy-terminal motif (ERLI), which is required for Drosophila cell polarity, and the Pals1 PDZ domain using crystallography and fluorescence polarization. Only the last four Crb residues contribute to Pals1 PDZ-domain binding affinity, with specificity contributed by conserved charged interactions. Comparison of the Crb-bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe side chain that gates access to the PDZ peptide-binding groove. Removal of this side chain enhances the binding affinity by more than fivefold, suggesting that access of Crb to Pals1 may be regulated by intradomain contacts or by protein–protein interaction.

  1. Canonical and Noncanonical Sites Determine NPT2A Binding Selectivity to NHERF1 PDZ1.

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    Tatyana Mamonova

    Full Text Available Na+/H+ Exchanger Regulatory Factor-1 (NHERF1 is a scaffolding protein containing 2 PDZ domains that coordinates the assembly and trafficking of transmembrane receptors and ion channels. Most target proteins harboring a C-terminus recognition motif bind more-or-less equivalently to the either PDZ domain, which contain identical core-binding motifs. However some substrates such as the type II sodium-dependent phosphate co-transporter (NPT2A, uniquely bind only one PDZ domain. We sought to define the structural determinants responsible for the specificity of interaction between NHERF1 PDZ domains and NPT2A. By performing all-atom/explicit-solvent molecular dynamics (MD simulations in combination with biological mutagenesis, fluorescent polarization (FP binding assays, and isothermal titration calorimetry (ITC, we found that in addition to canonical interactions of residues at 0 and -2 positions, Arg at the -1 position of NPT2A plays a critical role in association with Glu43 and His27 of PDZ1 that are absent in PDZ2. Experimentally introduced mutation in PDZ1 (Glu43Asp and His27Asn decreased binding to NPT2A. Conversely, introduction of Asp183Glu and Asn167His mutations in PDZ2 promoted the formation of favorable interactions yielding micromolar KDs. The results describe novel determinants within both the PDZ domain and outside the canonical PDZ-recognition motif that are responsible for discrimination of NPT2A between two PDZ domains. The results challenge general paradigms for PDZ recognition and suggest new targets for drug development.

  2. Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif

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    Launey Thomas

    2011-06-01

    Full Text Available Abstract Background The interactions between PDZ (PSD-95, Dlg, ZO-1 domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C- terminal ends of their binding partners. However, it remains little explored whether PDZ-binding motifs show any preferential location at the C-terminal ends of proteins, at genome-level. Results Here, we examined the distribution of the type-I (x-x-S/T-x-I/L/V or type-II (x-x-V-x-I/V PDZ-binding motifs in proteins encoded in the genomes of five different species (human, mouse, zebrafish, fruit fly and nematode. We first established that these PDZ-binding motifs are indeed preferentially present at their C-terminal ends. Moreover, we found specific amino acid (AA bias for the 'x' positions in the motifs at the C-terminal ends. In general, hydrophilic AAs were favored. Our genomics-based findings confirm and largely extend the results of previous interaction-based studies, allowing us to propose refined consensus sequences for all of the examined PDZ-binding motifs. An ontological analysis revealed that the refined motifs are functionally relevant since a large fraction of the proteins bearing the motif appear to be involved in signal transduction. Furthermore, co-precipitation experiments confirmed two new protein interactions predicted by our genomics-based approach. Finally, we show that influenza virus pathogenicity can be correlated with PDZ-binding motif, with high-virulence viral proteins bearing a refined PDZ-binding motif. Conclusions Our refined definition of PDZ-binding motifs should provide important clues for identifying functional PDZ-binding motifs and proteins involved in signal transduction.

  3. INVESTIGATING THE ROLE OF PDZ-DOMAIN INTERACTIONS FOR DOPAMINE TRANSPORTER FUNCTION

    DEFF Research Database (Denmark)

    Fog, Jacob; Vægter, Christian Bjerggaard; Gether, Ulrik

    canonical PDZ domain interactions with proteins such as PICK1. To clarify the actual role of PDZ domain interactions for DAT function we have expressed the wild type DAT and a number of C-terminal mutants either alone or together with PICK1 in HEK293, N2A neuroblastoma and PC12 cells. Data obtained from...

  4. Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?

    Science.gov (United States)

    James, Claire D; Roberts, Sally

    2016-01-18

    Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.

  5. Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait?

    Directory of Open Access Journals (Sweden)

    Claire D. James

    2016-01-01

    Full Text Available Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9, encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ interaction modules. In many cases (but not always, the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.

  6. Importance of a Conserved Lys/Arg Residue for Ligand/PDZ Domain Interactions as Examined by Protein Semisynthesis

    DEFF Research Database (Denmark)

    Pedersen, Søren W; Moran, Griffin E; Sereikaité, Vita

    2016-01-01

    PDZ domains are ubiquitous small protein domains that are mediators of numerous protein-protein interactions, and play a pivotal role in protein trafficking, synaptic transmission, and the assembly of signaling-transduction complexes. In recent years, PDZ domains have emerged as novel and exciting...... drug targets for diseases (in the brain in particular), so understanding the molecular details of PDZ domain interactions is of fundamental importance. PDZ domains bind to a protein partner at either a C-terminal peptide or internal peptide motifs. Here, we examined the importance of a conserved Lys...

  7. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    Science.gov (United States)

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  8. Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) scaffold multi-PDZ domain protein 1.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2009-12-01

    The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30% of olfactory receptors possess a classical post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) domain binding motif in their C-termini. PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 (MUPP1) is expressed in the apical compartment of olfactory sensory neurons. Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 + 2 of MUPP1 with the C-terminus of olfactory receptors in vitro. Moreover, the odorant-elicited calcium response of OR2AG1 showed a prolonged decay in MUPP1 small interfering RNA-treated cells. We have therefore elucidated the first building blocks of the putative \\'olfactosome\\

  9. Cooperative phosphoinositide and peptide binding by PSD-95/discs large/ZO-1 (PDZ) domain of polychaetoid, Drosophila zonulin.

    Science.gov (United States)

    Ivarsson, Ylva; Wawrzyniak, Anna Maria; Wuytens, Gunther; Kosloff, Mickey; Vermeiren, Elke; Raport, Marie; Zimmermann, Pascale

    2011-12-30

    PDZ domains are well known protein-protein interaction modules that, as part of multidomain proteins, assemble molecular complexes. Some PDZ domains have been reported to interact with membrane lipids, in particular phosphatidylinositol phosphates, but few studies have been aimed at elucidating the prevalence or the molecular details of such interactions. We screened 46 Drosophila PDZ domains for phosphoinositide-dependent cellular localization and discovered that the second PDZ domain of polychaetoid (Pyd PDZ2) interacts with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) at the plasma membrane. Surface plasmon resonance binding experiments with recombinant protein established that Pyd PDZ2 interacts with phosphatidylinositol phosphates with apparent affinities in the micromolar range. Electrostatic interactions involving an extended positively charged surface of Pyd PDZ2 are crucial for the PtdIns(4,5)P(2)-dependent membrane interactions as shown by a combination of three-dimensional modeling, mutagenesis, binding, and localization studies. In vivo localization studies further suggested that both lipid and peptide binding contribute to membrane localization. We identified the transmembrane protein Crumbs as a Pyd PDZ2 ligand and probed the relation between peptide and PtdIns(4,5)P(2) binding. Contrary to the prevalent view on PDZ/peptide/lipid binding, we did not find competition between peptide and lipid ligands. Instead, preloading the protein with the 10-mer Crb3 peptide increased the apparent affinity of Pyd PDZ2 for PtdIns(4,5)P(2) 6-fold. Our results suggest that membrane localization of Pyd PDZ2 may be driven by a combination of peptide and PtdIns(4,5)P(2) binding, which raises the intriguing possibility that the domain may coordinate protein- and phospholipid-mediated signals.

  10. Characterization of diverse internal binding specificities of PDZ domains by yeast two-hybrid screening of a special peptide library.

    Science.gov (United States)

    Mu, Yi; Cai, Pengfei; Hu, Siqi; Ma, Sucan; Gao, Youhe

    2014-01-01

    Protein-protein interactions (PPIs) are essential events to play important roles in a series of biological processes. There are probably more ways of PPIs than we currently realized. Structural and functional investigations of weak PPIs have lagged behind those of strong PPIs due to technical difficulties. Weak PPIs are often short-lived, which may result in more dynamic signals with important biological roles within and/or between cells. For example, the characteristics of PSD-95/Dlg/ZO-1 (PDZ) domain binding to internal sequences, which are primarily weak interactions, have not yet been systematically explored. In the present study, we constructed a nearly random octapeptide yeast two-hybrid library. A total of 24 PDZ domains were used as baits for screening the library. Fourteen of these domains were able to bind internal PDZ-domain binding motifs (PBMs), and PBMs screened for nine PDZ domains exhibited strong preferences. Among 11 PDZ domains that have not been reported their internal PBM binding ability, six were confirmed to bind internal PBMs. The first PDZ domain of LNX2, which has not been reported to bind C-terminal PBMs, was found to bind internal PBMs. These results suggest that the internal PBMs binding ability of PDZ domains may have been underestimated. The data provided diverse internal binding properties for several PDZ domains that may help identify their novel binding partners.

  11. A fluorescence polarization based screening assay for identification of small molecule inhibitors of the PICK1 PDZ domain

    DEFF Research Database (Denmark)

    Thorsen, Thor S; Madsen, Kenneth L; Dyhring, Tino

    2011-01-01

    PDZ (PSD-95/Discs-large/ZO-1 homology) domains represent putative targets in several diseases including cancer, stroke, addiction and neuropathic pain. Here we describe the application of a simple and fast screening assay based on fluorescence polarization (FP) to identify inhibitors of the PDZ...

  12. Computational design of selective peptides to discriminate between similar PDZ domains in an oncogenic pathway.

    Science.gov (United States)

    Zheng, Fan; Jewell, Heather; Fitzpatrick, Jeremy; Zhang, Jian; Mierke, Dale F; Grigoryan, Gevorg

    2015-01-30

    Reagents that target protein-protein interactions to rewire signaling are of great relevance in biological research. Computational protein design may offer a means of creating such reagents on demand, but methods for encoding targeting selectivity are sorely needed. This is especially challenging when targeting interactions with ubiquitous recognition modules--for example, PDZ domains, which bind C-terminal sequences of partner proteins. Here we consider the problem of designing selective PDZ inhibitor peptides in the context of an oncogenic signaling pathway, in which two PDZ domains (NHERF-2 PDZ2-N2P2 and MAGI-3 PDZ6-M3P6) compete for a receptor C-terminus to differentially modulate oncogenic activities. Because N2P2 has been shown to increase tumorigenicity and M3P6 to decreases it, we sought to design peptides that inhibit N2P2 without affecting M3P6. We developed a structure-based computational design framework that models peptide flexibility in binding yet is efficient enough to rapidly analyze tradeoffs between affinity and selectivity. Designed peptides showed low-micromolar inhibition constants for N2P2 and no detectable M3P6 binding. Peptides designed for reverse discrimination bound M3P6 tighter than N2P2, further testing our technology. Experimental and computational analysis of selectivity determinants revealed significant indirect energetic coupling in the binding site. Successful discrimination between N2P2 and M3P6, despite their overlapping binding preferences, is highly encouraging for computational approaches to selective PDZ targeting, especially because design relied on a homology model of M3P6. Still, we demonstrate specific deficiencies of structural modeling that must be addressed to enable truly robust design. The presented framework is general and can be applied in many scenarios to engineer selective targeting. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. An expanded view of the protein folding landscape of PDZ domains

    DEFF Research Database (Denmark)

    Hultqvist, Greta; Pedersen, Søren W; Chi, Celestine N.

    2012-01-01

    state. In light of these results, we have re-analyzed previous folding data on PDZ domains and present a unified folding mechanism with three distinct transition states separated by two high-energy intermediates. Our data show that sequence composition tunes the relative stabilities of folding...

  14. PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95

    DEFF Research Database (Denmark)

    Møller, Thor C; Wirth, Volker F; Roberts, Nina Ingerslev

    2013-01-01

    G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present...

  15. An in silico analysis of the binding modes and binding affinities of small molecule modulators of PDZ-peptide interactions.

    Directory of Open Access Journals (Sweden)

    Garima Tiwari

    Full Text Available Inhibitors of PDZ-peptide interactions have important implications in a variety of biological processes including treatment of cancer and Parkinson's disease. Even though experimental studies have reported characterization of peptidomimetic inhibitors of PDZ-peptide interactions, the binding modes for most of them have not been characterized by structural studies. In this study we have attempted to understand the structural basis of the small molecule-PDZ interactions by in silico analysis of the binding modes and binding affinities of a set of 38 small molecules with known K(i or K(d values for PDZ2 and PDZ3 domains of PSD-95 protein. These two PDZ domains show differential selectivity for these compounds despite having a high degree of sequence similarity and almost identical peptide binding pockets. Optimum binding modes for these ligands for PDZ2 and PDZ3 domains were identified by using a novel combination of semi-flexible docking and explicit solvent molecular dynamics (MD simulations. Analysis of the binding modes revealed most of the peptidomimectic ligands which had high K(i or K(d moved away from the peptide binding pocket, while ligands with high binding affinities remained in the peptide binding pocket. The differential specificities of the PDZ2 and PDZ3 domains primarily arise from differences in the conformation of the loop connecting βB and βC strands, because this loop interacts with the N-terminal chemical moieties of the ligands. We have also computed the MM/PBSA binding free energy values for these 38 compounds with both the PDZ domains from multiple 5 ns MD trajectories on each complex i.e. a total of 228 MD trajectories of 5 ns length each. Interestingly, computational binding free energies show good agreement with experimental binding free energies with a correlation coefficient of approximately 0.6. Thus our study demonstrates that combined use of docking and MD simulations can help in identification of potent inhibitors

  16. The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

    Science.gov (United States)

    Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

    2000-01-01

    Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

  17. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

    Science.gov (United States)

    Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H; Burk, Robert D

    2015-06-01

    In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

  18. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche

    Science.gov (United States)

    Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H.; Burk, Robert D.

    2015-01-01

    In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution. PMID:26086730

  19. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

    Directory of Open Access Journals (Sweden)

    Koenraad Van Doorslaer

    2015-06-01

    Full Text Available In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

  20. Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

  1. Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions

    DEFF Research Database (Denmark)

    Bach, Anders

    2015-01-01

    ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. Here, we investigate the proposed mechanism of action of ZL006 and IC87201 using biochemical...... by interacting with the β-finger of nNOS-PDZ. Our findings have implications for further medicinal chemistry efforts of ZL006, IC87201 and analogues, and challenge the general and widespread view on their mechanism of action....

  2. Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments.

    Directory of Open Access Journals (Sweden)

    Ylva Ivarsson

    Full Text Available BACKGROUND: PDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs, important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited. METHODOLOGY/PRINCIPAL FINDINGS: We screened the human proteome for PtdInsPs interacting PDZ domains by a combination of in vivo cell-localization studies and in vitro dot blot and Surface Plasmon Resonance (SPR experiments using synthetic lipids and recombinant proteins. We found that PtdInsPs interactions contribute to the cellular distribution of some PDZ domains, intriguingly also in nuclear organelles, and that a significant subgroup of PDZ domains interacts with PtdInsPs with affinities in the low-to-mid micromolar range. In vitro specificity for the head group is low, but with a trend of higher affinities for more phosphorylated PtdInsPs species. Other membrane lipids can assist PtdInsPs-interactions. PtdInsPs-interacting PDZ domains have generally high pI values and contain characteristic clusters of basic residues, hallmarks that may be used to predict additional PtdInsPs interacting PDZ domains. In tripartite binding experiments we established that peptide binding can either compete or cooperate with PtdInsPs binding depending on the combination of ligands. CONCLUSIONS/SIGNIFICANCE: Our screen substantially expands the set of PtdInsPs interacting PDZ domains, and shows that a full understanding of the biology of PDZ proteins will require a comprehensive insight into the intricate relationships between PDZ domains and their peptide and lipid ligands.

  3. The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy

    Directory of Open Access Journals (Sweden)

    Ketaki Ganti

    2015-07-01

    Full Text Available Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.

  4. Contribution of buried aspartic acid to the stability of the PDZ2 protein

    International Nuclear Information System (INIS)

    Jayasimha, Pruthvi; Shanmuganathan, Aranganathan; Suladze, Saba; Makhatadze, George I.

    2012-01-01

    Highlights: ► Buried Asp residues on average form 2.5 to 3 hydrogen bonds and/or 0.8 salt bridges. ► Contribution of buried Asp to stability was estimated using model protein PDZ2. ► The energetic contribution of Asp56 to PDZ2 stability estimated to be 18 kJ · mol −1 . ► Findings are discussed in terms of contribution of Asp residues to protein stability. - Abstract: Statistical analysis of protein structures shows that buried aspartic acid residues on average form 2.5 to 3 hydrogen bonds and/or 0.8 potential ionic interactions with other protein groups. To estimate the energetic contribution of such buried groups to the Gibbs free energy of proteins, we measured the effects of amino acid substitutions of D56 in a model protein PDZ2 on its stability. We used temperature-induced unfolding monitored by DSC and denaturant-induced unfolding monitored by the changes in fluorescence intensity. We find that all substitutions of D56 lead to protein unfolding, thus suggesting that this buried hydrogen bonded aspartic acid has a significant contribution to the stability. To quantify the changes in the Gibbs free energy, one of the variants, D56N was stabilized by addition of the protective osmolyte TMAO. Comparison of the stability of the D56N variant with the wild-type PDZ2 in the presence and absence of TMAO allowed us to estimate the contribution of D56 to the protein stability to be 18 kJ · mol −1 . These findings are discussed in terms of contribution of buried ionizable groups to protein stability.

  5. Change in Allosteric Network Affects Binding Affinities of PDZ Domains: Analysis through Perturbation Response Scanning

    Science.gov (United States)

    Gerek, Z. Nevin; Ozkan, S. Banu

    2011-01-01

    The allosteric mechanism plays a key role in cellular functions of several PDZ domain proteins (PDZs) and is directly linked to pharmaceutical applications; however, it is a challenge to elaborate the nature and extent of these allosteric interactions. One solution to this problem is to explore the dynamics of PDZs, which may provide insights about how intramolecular communication occurs within a single domain. Here, we develop an advancement of perturbation response scanning (PRS) that couples elastic network models with linear response theory (LRT) to predict key residues in allosteric transitions of the two most studied PDZs (PSD-95 PDZ3 domain and hPTP1E PDZ2 domain). With PRS, we first identify the residues that give the highest mean square fluctuation response upon perturbing the binding sites. Strikingly, we observe that the residues with the highest mean square fluctuation response agree with experimentally determined residues involved in allosteric transitions. Second, we construct the allosteric pathways by linking the residues giving the same directional response upon perturbation of the binding sites. The predicted intramolecular communication pathways reveal that PSD-95 and hPTP1E have different pathways through the dynamic coupling of different residue pairs. Moreover, our analysis provides a molecular understanding of experimentally observed hidden allostery of PSD-95. We show that removing the distal third alpha helix from the binding site alters the allosteric pathway and decreases the binding affinity. Overall, these results indicate that (i) dynamics plays a key role in allosteric regulations of PDZs, (ii) the local changes in the residue interactions can lead to significant changes in the dynamics of allosteric regulations, and (iii) this might be the mechanism that each PDZ uses to tailor their binding specificities regulation. PMID:21998559

  6. Oracle, a novel PDZ-LIM domain protein expressed in heart and skeletal muscle.

    Science.gov (United States)

    Passier, R; Richardson, J A; Olson, E N

    2000-04-01

    In order to identify novel genes enriched in adult heart, we performed a subtractive hybridization for genes expressed in mouse heart but not in skeletal muscle. We identified two alternative splicing variants of a novel PDZ-LIM domain protein, which we named Oracle. Both variants contain a PDZ domain at the amino-terminus and three LIM domains at the carboxy-terminus. Highest homology of Oracle was found with the human and rat enigma proteins in the PDZ domain (62 and 61%, respectively) and in the LIM domains (60 and 69%, respectively). By Northern hybridization analysis, we showed that expression is highest in adult mouse heart, low in skeletal muscle and undetectable in other adult mouse tissues. In situ hybridization in mouse embryos confirmed and extended these data by showing high expression of Oracle mRNA in atrial and ventricular myocardial cells from E8.5. From E9.5 low expression of Oracle mRNA was detectable in myotomes. These data suggest a role for Oracle in the early development and function of heart and skeletal muscle.

  7. Insights into the molecular evolution of the PDZ/LIM family and identification of a novel conserved protein motif.

    Directory of Open Access Journals (Sweden)

    Aartjan J W Te Velthuis

    Full Text Available The PDZ and LIM domain-containing protein family is encoded by a diverse group of genes whose phylogeny has currently not been analyzed. In mammals, ten genes are found that encode both a PDZ- and one or several LIM-domains. These genes are: ALP, RIL, Elfin (CLP36, Mystique, Enigma (LMP-1, Enigma homologue (ENH, ZASP (Cypher, Oracle, LMO7 and the two LIM domain kinases (LIMK1 and LIMK2. As conventional alignment and phylogenetic procedures of full-length sequences fell short of elucidating the evolutionary history of these genes, we started to analyze the PDZ and LIM domain sequences themselves. Using information from most sequenced eukaryotic lineages, our phylogenetic analysis is based on full-length cDNA-, EST-derived- and genomic- PDZ and LIM domain sequences of over 25 species, ranging from yeast to humans. Plant and protozoan homologs were not found. Our phylogenetic analysis identifies a number of domain duplication and rearrangement events, and shows a single convergent event during evolution of the PDZ/LIM family. Further, we describe the separation of the ALP and Enigma subfamilies in lower vertebrates and identify a novel consensus motif, which we call 'ALP-like motif' (AM. This motif is highly-conserved between ALP subfamily proteins of diverse organisms. We used here a combinatorial approach to define the relation of the PDZ and LIM domain encoding genes and to reconstruct their phylogeny. This analysis allowed us to classify the PDZ/LIM family and to suggest a meaningful model for the molecular evolution of the diverse gene architectures found in this multi-domain family.

  8. ER EXPORT AND SURFACE TARGETING OF THE DOPAMINE TRANSPORTER ARE DEPENDENT ON THE DISTAL C-TERMINUS BUT OCCURS INDEPENDENTLY OF PDZ DOMAIN INTERACTIONS

    DEFF Research Database (Denmark)

    Bjerggaard(Vægter), Christian; Loland, Claus; Hastrup, Hanne

    . Neuron 2001, 30:121-34). As expected, we find that deletion of the PDZ binding sequence (LKV) or substitution with three histidines resulted in retention of hDAT in the ER in both HEK293 and N2A neuroblastoma cells. However, substitution of LKV with the type 2 PDZ binding sequence SLL of the beta2...

  9. The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation.

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    Sarah V Consonni

    Full Text Available PDZGEF is a guanine nucleotide exchange factor for the small G protein Rap. It was recently found that PDZGEF contributes to establishment of intestinal epithelial polarity downstream of the kinase Lkb1. By binding to phosphatidic acid enriched at the apical membrane, PDZGEF locally activates Rap2a resulting in induction of brush border formation via a pathway that includes the polarity players TNIK, Mst4 and Ezrin. Here we show that the PDZ domain of PDZGEF is essential and sufficient for targeting PDZGEF to the apical membrane of polarized intestinal epithelial cells. Inhibition of PLD and consequently production of phosphatidic acid inhibitis targeting of PDZGEF to the plasma membrane. Furthermore, localization requires specific positively charged residues within the PDZ domain. We conclude that local accumulation of PDZGEF at the apical membrane during establishment of epithelial polarity is mediated by electrostatic interactions between positively charged side chains in the PDZ domain and negatively charged phosphatidic acid.

  10. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    International Nuclear Information System (INIS)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun; Nishina, Hiroshi

    2014-01-01

    Highlights: •Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. •The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. •Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription

  11. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    Energy Technology Data Exchange (ETDEWEB)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun, E-mail: hirayama.dbio@mri.tmd.ac.jp; Nishina, Hiroshi, E-mail: nishina.dbio@mri.tmd.ac.jp

    2014-01-17

    Highlights: •Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. •The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. •Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.

  12. PDZ-containing proteins: alternative splicing as a source of functional diversity.

    Science.gov (United States)

    Sierralta, Jimena; Mendoza, Carolina

    2004-12-01

    Scaffold proteins allow specific protein complexes to be assembled in particular regions of the cell at which they organize subcellular structures and signal transduction complexes. This characteristic is especially important for neurons, which are highly polarized cells. Among the domains contained by scaffold proteins, the PSD-95, Discs-large, ZO-1 (PDZ) domains are of particular relevance in signal transduction processes and maintenance of neuronal and epithelial polarity. These domains are specialized in the binding of the carboxyl termini of proteins allowing membrane proteins to be localized by the anchoring to the cytoskeleton mediated by PDZ-containing scaffold proteins. In vivo studies carried out in Drosophila have taught that the role of many scaffold proteins is not limited to a single process; thus, in many cases the same genes are expressed in different tissues and participate in apparently very diverse processes. In addition to the differential expression of interactors of scaffold proteins, the expression of variants of these molecular scaffolds as the result of the alternative processing of the genes that encode them is proving to be a very important source of variability and complexity on a main theme. Alternative splicing in the nervous system is well documented, where specific isoforms play roles in neurotransmission, ion channel function, neuronal cell recognition, and are developmentally regulated making it a major mechanism of functional diversity. Here we review the current state of knowledge about the diversity and the known function of PDZ-containing proteins in Drosophila with emphasis in the role played by alternatively processed forms in the diversity of functions attributed to this family of proteins.

  13. Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins

    Directory of Open Access Journals (Sweden)

    Nagasaka Kazunori

    2011-01-01

    Full Text Available Abstract The Influenza A virus non-structural protein 1 (NS1 is a multifunctional virulence factor with several protein-protein interaction domains, involved in preventing apoptosis of the infected cell and in evading the interferon response. In addition, the majority of influenza A virus NS1 proteins have a class I PDZ-binding motif at the C-terminus, and this itself has been shown to be a virulence determinant. In the majority of human influenza NS1 proteins the consensus motif is RSxV: in avian NS1 it is ESxV. Of the few human strains that have the avian motif, all were from very high mortality outbreaks of the disease. Previous work has shown that minor differences in PDZ-binding motifs can have major effects on the spectrum of cellular proteins targeted. In this study we analyse the effect of these differences upon the binding of Influenza A virus NS1 protein to a range of cellular proteins involved in polarity and signal transduction.

  14. Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions

    DEFF Research Database (Denmark)

    Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E

    2017-01-01

    The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effec...

  15. Computational design of a PDZ domain peptide inhibitor that rescues CFTR activity.

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    Kyle E Roberts

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR is an epithelial chloride channel mutated in patients with cystic fibrosis (CF. The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators ("potentiators" and "correctors", but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL, which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called "stabilizers" that rescue ΔF508-CFTR activity. To design the "stabilizers", we extended our structural ensemble-based computational protein redesign algorithm K* to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01 binds six-fold more tightly than the previous best hexamer (iCAL35, and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods.

  16. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions.

    Science.gov (United States)

    Bjerggaard, Christian; Fog, Jacob U; Hastrup, Hanne; Madsen, Kenneth; Loland, Claus J; Javitch, Jonathan A; Gether, Ulrik

    2004-08-04

    The human dopamine transporter (hDAT) contains a C-terminal type 2 PDZ (postsynaptic density 95/Discs large/zona occludens 1) domain-binding motif (LKV) known to interact with PDZ domain proteins such as PICK1 (protein interacting with C-kinase 1). As reported previously, we found that, after deletion of this motif, hDAT was retained in the endoplasmic reticulum (ER) of human embryonic kidney (HEK) 293 and Neuro2A cells, suggesting that PDZ domain interactions might be critical for hDAT targeting. Nonetheless, substitution of LKV with SLL, the type 1 PDZ-binding sequence from the beta2-adrenergic receptor, did not disrupt plasma membrane targeting. Moreover, the addition of an alanine to the hDAT C terminus (+Ala), resulting in an LKVA termination sequence, or substitution of LKV with alanines (3xAla_618-620) prevented neither plasma membrane targeting nor targeting into sprouting neurites of differentiated N2A cells. The inability of +Ala and 3xAla_618-620 to bind PDZ domains was confirmed by lack of colocalization with PICK1 in cotransfected HEK293 cells and by the inability of corresponding C-terminal fusion proteins to pull down purified PICK1. Thus, although residues in the hDAT C terminus are indispensable for proper targeting, PDZ domain interactions are not required. By progressive substitutions with beta2-adrenergic receptor sequence, and by triple-alanine substitutions in the hDAT C terminus, we examined the importance of epitopes preceding the LKV motif. Substitution of RHW(615-617) with alanines caused retention of the transporter in the ER despite preserved ability of this mutant to bind PICK1. We propose dual roles of the hDAT C terminus: a role independent of PDZ interactions for ER export and surface targeting, and a not fully clarified role involving PDZ interactions with proteins such as PICK1.

  17. Common features in the unfolding and misfolding of PDZ domains and beyond: the modulatory effect of domain swapping and extra-elements.

    Science.gov (United States)

    Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C

    2016-01-12

    PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.

  18. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Hansen, Freja Herborg; Sørensen, Gunnar

    2013-01-01

    believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine......The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence...... transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization...

  19. A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding Specificity of the Tiam1 PDZ Domain.

    Science.gov (United States)

    Panel, Nicolas; Sun, Young Joo; Fuentes, Ernesto J; Simonson, Thomas

    2017-01-01

    PDZ domains generally bind short amino acid sequences at the C-terminus of target proteins, and short peptides can be used as inhibitors or model ligands. Here, we used experimental binding assays and molecular dynamics simulations to characterize 51 complexes involving the Tiam1 PDZ domain and to test the performance of a semi-empirical free energy function. The free energy function combined a Poisson-Boltzmann (PB) continuum electrostatic term, a van der Waals interaction energy, and a surface area term. Each term was empirically weighted, giving a Linear Interaction Energy or "PB/LIE" free energy. The model yielded a mean unsigned deviation of 0.43 kcal/mol and a Pearson correlation of 0.64 between experimental and computed free energies, which was superior to a Null model that assumes all complexes have the same affinity. Analyses of the models support several experimental observations that indicate the orientation of the α 2 helix is a critical determinant for peptide specificity. The models were also used to predict binding free energies for nine new variants, corresponding to point mutants of the Syndecan1 and Caspr4 peptides. The predictions did not reveal improved binding; however, they suggest that an unnatural amino acid could be used to increase protease resistance and peptide lifetimes in vivo . The overall performance of the model should allow its use in the design of new PDZ ligands in the future.

  20. The Role of Backbone Hydrogen Bonds in the Transition State for Protein Folding of a PDZ Domain.

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    Søren W. Pedersen

    Full Text Available Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.

  1. A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding Specificity of the Tiam1 PDZ Domain

    Directory of Open Access Journals (Sweden)

    Nicolas Panel

    2017-09-01

    Full Text Available PDZ domains generally bind short amino acid sequences at the C-terminus of target proteins, and short peptides can be used as inhibitors or model ligands. Here, we used experimental binding assays and molecular dynamics simulations to characterize 51 complexes involving the Tiam1 PDZ domain and to test the performance of a semi-empirical free energy function. The free energy function combined a Poisson-Boltzmann (PB continuum electrostatic term, a van der Waals interaction energy, and a surface area term. Each term was empirically weighted, giving a Linear Interaction Energy or “PB/LIE” free energy. The model yielded a mean unsigned deviation of 0.43 kcal/mol and a Pearson correlation of 0.64 between experimental and computed free energies, which was superior to a Null model that assumes all complexes have the same affinity. Analyses of the models support several experimental observations that indicate the orientation of the α2 helix is a critical determinant for peptide specificity. The models were also used to predict binding free energies for nine new variants, corresponding to point mutants of the Syndecan1 and Caspr4 peptides. The predictions did not reveal improved binding; however, they suggest that an unnatural amino acid could be used to increase protease resistance and peptide lifetimes in vivo. The overall performance of the model should allow its use in the design of new PDZ ligands in the future.

  2. Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1 Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif.

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    Julia Bender

    Full Text Available The corticotropin-releasing hormone receptor type 1 (CRHR1 plays an important role in orchestrating neuroendocrine, behavioral, and autonomic responses to stress. To identify molecules capable of directly modulating CRHR1 signaling, we performed a yeast-two-hybrid screen using the C-terminal intracellular tail of the receptor as bait. We identified several members of the membrane-associated guanylate kinase (MAGUK family: postsynaptic density protein 95 (PSD95, synapse-associated protein 97 (SAP97, SAP102 and membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2. CRHR1 is co-expressed with the identified MAGUKs and with the additionally investigated PSD93 in neurons of the adult mouse brain and in primary hippocampal neurons, supporting the probability of a physiological interaction in vivo. The C-terminal PDZ (PSD-95, discs large, zona occludens 1 binding motif of CRHR1 is essential for its physical interaction with MAGUKs, as revealed by the CRHR1-STAVA mutant, which harbors a functionally impaired PDZ binding motif. The imitation of a phosphorylation at Thr413 within the PDZ binding motif also disrupted the interaction with MAGUKs. In contrast, distinct PDZ domains within the identified MAGUKs are involved in the interactions. Expression of CRHR1 in primary neurons demonstrated its localization throughout the neuronal plasma membrane, including the excitatory post synapse, where the receptor co-localized with PSD95 and SAP97. The co-expression of CRHR1 and respective interacting MAGUKs in HEK293 cells resulted in a clustered subcellular co-localization which required an intact PDZ binding motif. In conclusion, our study characterized the PDZ binding motif-mediated interaction of CRHR1 with multiple MAGUKs, which directly affects receptor function.

  3. A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.

    Science.gov (United States)

    Kalay, E; de Brouwer, A P M; Caylan, R; Nabuurs, S B; Wollnik, B; Karaguzel, A; Heister, J G A M; Erdol, H; Cremers, F P M; Cremers, C W R J; Brunner, H G; Kremer, H

    2005-12-01

    Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.

  4. δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions*

    Science.gov (United States)

    Yuan, Li; Seong, Eunju; Beuscher, James L.; Arikkath, Jyothi

    2015-01-01

    The ability of neurons to maintain spine architecture and modulate it in response to synaptic activity is a crucial component of the cellular machinery that underlies information storage in pyramidal neurons of the hippocampus. Here we show a critical role for δ-catenin, a component of the cadherin-catenin cell adhesion complex, in regulating spine head width and length in pyramidal neurons of the hippocampus. The loss of Ctnnd2, the gene encoding δ-catenin, has been associated with the intellectual disability observed in the cri du chat syndrome, suggesting that the functional roles of δ-catenin are vital for neuronal integrity and higher order functions. We demonstrate that loss of δ-catenin in a mouse model or knockdown of δ-catenin in pyramidal neurons compromises spine head width and length, without altering spine dynamics. This is accompanied by a reduction in the levels of synaptic N-cadherin. The ability of δ-catenin to modulate spine architecture is critically dependent on its ability to interact with cadherin and PDZ domain-containing proteins. We propose that loss of δ-catenin during development perturbs synaptic architecture leading to developmental aberrations in neural circuit formation that contribute to the learning disabilities in a mouse model and humans with cri du chat syndrome. PMID:25724647

  5. δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions.

    Science.gov (United States)

    Yuan, Li; Seong, Eunju; Beuscher, James L; Arikkath, Jyothi

    2015-04-24

    The ability of neurons to maintain spine architecture and modulate it in response to synaptic activity is a crucial component of the cellular machinery that underlies information storage in pyramidal neurons of the hippocampus. Here we show a critical role for δ-catenin, a component of the cadherin-catenin cell adhesion complex, in regulating spine head width and length in pyramidal neurons of the hippocampus. The loss of Ctnnd2, the gene encoding δ-catenin, has been associated with the intellectual disability observed in the cri du chat syndrome, suggesting that the functional roles of δ-catenin are vital for neuronal integrity and higher order functions. We demonstrate that loss of δ-catenin in a mouse model or knockdown of δ-catenin in pyramidal neurons compromises spine head width and length, without altering spine dynamics. This is accompanied by a reduction in the levels of synaptic N-cadherin. The ability of δ-catenin to modulate spine architecture is critically dependent on its ability to interact with cadherin and PDZ domain-containing proteins. We propose that loss of δ-catenin during development perturbs synaptic architecture leading to developmental aberrations in neural circuit formation that contribute to the learning disabilities in a mouse model and humans with cri du chat syndrome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

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    Nikhil Sangith

    2014-01-01

    Full Text Available PSMD9 (Proteasome Macropain non-ATPase subunit 9, a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a proteins with conserved C-termini may share common functions and (b PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein, S14 (a ribosomal protein, CSH1 (a growth hormone, E12 (a transcription factor and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions.

  7. The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo

    Science.gov (United States)

    Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.

    2003-01-01

    Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014

  8. G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms.

    Science.gov (United States)

    Gonzalez de Valdivia, Ernesto; Broselid, Stefan; Kahn, Robin; Olde, Björn; Leeb-Lundberg, L M Fredrik

    2017-06-16

    G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of G i/o Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin as well as by wortmannin but not by AG1478, indicating that G i/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two G i/o -mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and a PDZ-independent G-1-stimulated mechanism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.

    Science.gov (United States)

    Pérès, Eléonore; Blin, Juliana; Ricci, Emiliano P; Artesi, Maria; Hahaut, Vincent; Van den Broeke, Anne; Corbin, Antoine; Gazzolo, Louis; Ratner, Lee; Jalinot, Pierre; Duc Dodon, Madeleine

    2018-03-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization.

  10. Crystallization and Preliminary Diffraction Analysis of the CAL PDZ Domain in Complex with a Selective Peptide Inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    J Amacher; P Cushing; J Weiner; D Madden

    2011-12-31

    Cystic fibrosis (CF) is associated with loss-of-function mutations in the CF transmembrane conductance regulator (CFTR), which regulates epithelial fluid and ion homeostasis. The CFTR cytoplasmic C-terminus interacts with a number of PDZ (PSD-95/Dlg/ZO-1) proteins that modulate its intracellular trafficking and chloride-channel activity. Among these, the CFTR-associated ligand (CAL) has a negative effect on apical-membrane expression levels of the most common disease-associated mutant {Delta}F508-CFTR, making CAL a candidate target for the treatment of CF. A selective peptide inhibitor of the CAL PDZ domain (iCAL36) has recently been developed and shown to stabilize apical expression of {Delta}F508-CFTR, enhancing net chloride-channel activity, both alone and in combination with the folding corrector corr-4a. As a basis for structural studies of the CAL-iCAL36 interaction, a purification protocol has been developed that increases the oligomeric homogeneity of the protein. Here, the cocrystallization of the complex in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 35.9, b = 47.7, c = 97.3 {angstrom}, is reported. The crystals diffracted to 1.4 {angstrom} resolution. Based on the calculated Matthews coefficient (1.96 {angstrom}{sup 3} Da{sup -1}), it appears that the asymmetric unit contains two complexes.

  11. An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets.

    Science.gov (United States)

    Nisar, Shaista; Daly, Martina E; Federici, Augusto B; Artoni, Andrea; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2011-11-17

    The platelet P2Y(12) purinoceptor (P2Y(12)R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y(12)R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)-binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y(12)R (P341A) that is associated with reduced expression of the P2Y(12)R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y(12)R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic.

  12. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, K.; Pfeiferová, L.; Boušová, Kristýna; Bednárová, L.; Obšilová, Veronika; Vondrášek, J.

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:67985823 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins * molecular dynamics simulation * circular dichroism Subject RIV: BO - Biophysics Impact factor: 2.289, year: 2016

  13. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, Kirubakaran; Pfeiferová, Lucie; Boušová, Kristýna; Bednárová, Lucie; Obšilová, V.; Vondrášek, Jiří

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  14. A PDZ-Like Motif in the Biliary Transporter ABCB4 Interacts with the Scaffold Protein EBP50 and Regulates ABCB4 Cell Surface Expression.

    Directory of Open Access Journals (Sweden)

    Quitterie Venot

    Full Text Available ABCB4/MDR3, a member of the ABC superfamily, is an ATP-dependent phosphatidylcholine translocator expressed at the canalicular membrane of hepatocytes. Defects in the ABCB4 gene are associated with rare biliary diseases. It is essential to understand the mechanisms of its canalicular membrane expression in particular for the development of new therapies. The stability of several ABC transporters is regulated through their binding to PDZ (PSD95/DglA/ZO-1 domain-containing proteins. ABCB4 protein ends by the sequence glutamine-asparagine-leucine (QNL, which shows some similarity to PDZ-binding motifs. The aim of our study was to assess the potential role of the QNL motif on the surface expression of ABCB4 and to determine if PDZ domain-containing proteins are involved. We found that truncation of the QNL motif decreased the stability of ABCB4 in HepG2-transfected cells. The deleted mutant ABCB4-ΔQNL also displayed accelerated endocytosis. EBP50, a PDZ protein highly expressed in the liver, strongly colocalized and coimmunoprecipitated with ABCB4, and this interaction required the QNL motif. Down-regulation of EBP50 by siRNA or by expression of an EBP50 dominant-negative mutant caused a significant decrease in the level of ABCB4 protein expression, and in the amount of ABCB4 localized at the canalicular membrane. Interaction of ABCB4 with EBP50 through its PDZ-like motif plays a critical role in the regulation of ABCB4 expression and stability at the canalicular plasma membrane.

  15. PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice

    Science.gov (United States)

    Artesi, Maria; Jalinot, Pierre

    2018-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization. PMID:29566098

  16. Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains

    DEFF Research Database (Denmark)

    Haq, S Raza; Chi, Celestine N; Bach, Anders

    2012-01-01

    Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. We have here...... used short peptides as a model system for intrinsically disordered proteins. Linear free-energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate......-limiting barrier for binding, in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins towards their targets are generally...

  17. Machine learning approaches to evaluate correlation patterns in allosteric signaling: A case study of the PDZ2 domain

    Science.gov (United States)

    Botlani, Mohsen; Siddiqui, Ahnaf; Varma, Sameer

    2018-06-01

    Many proteins are regulated by dynamic allostery wherein regulator-induced changes in structure are comparable with thermal fluctuations. Consequently, understanding their mechanisms requires assessment of relationships between and within conformational ensembles of different states. Here we show how machine learning based approaches can be used to simplify this high-dimensional data mining task and also obtain mechanistic insight. In particular, we use these approaches to investigate two fundamental questions in dynamic allostery. First, how do regulators modify inter-site correlations in conformational fluctuations (Cij)? Second, how are regulator-induced shifts in conformational ensembles at two different sites in a protein related to each other? We address these questions in the context of the human protein tyrosine phosphatase 1E's PDZ2 domain, which is a model protein for studying dynamic allostery. We use molecular dynamics to generate conformational ensembles of the PDZ2 domain in both the regulator-bound and regulator-free states. The employed protocol reproduces methyl deuterium order parameters from NMR. Results from unsupervised clustering of Cij combined with flow analyses of weighted graphs of Cij show that regulator binding significantly alters the global signaling network in the protein; however, not by altering the spatial arrangement of strongly interacting amino acid clusters but by modifying the connectivity between clusters. Additionally, we find that regulator-induced shifts in conformational ensembles, which we evaluate by repartitioning ensembles using supervised learning, are, in fact, correlated. This correlation Δij is less extensive compared to Cij, but in contrast to Cij, Δij depends inversely on the distance from the regulator binding site. Assuming that Δij is an indicator of the transduction of the regulatory signal leads to the conclusion that the regulatory signal weakens with distance from the regulatory site. Overall, this

  18. PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein augments the transforming activity in a rat fibroblast cell line

    International Nuclear Information System (INIS)

    Hirata, Akira; Higuchi, Masaya; Niinuma, Akiko; Ohashi, Minako; Fukushi, Masaya; Oie, Masayasu; Akiyama, Tetsu; Tanaka, Yuetsu; Gejyo, Fumitake; Fujii, Masahiro

    2004-01-01

    While human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL), HTLV-2 has not been reported to be associated with such malignant leukemias. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) to form multiple large colonies in soft agar, and this activity is much greater than that of HTLV-2 Tax2. We have demonstrated here that the increased number of transformed colonies induced by Tax1 relative to Tax2 was mediated by a PDZ domain-binding motif (PBM) in Tax1, which is absent in Tax2. Tax1 PBM mediated the interaction of Tax1 with the discs large (Dlg) tumor suppressor containing PDZ domains, and the interaction correlated well with the transforming activities of Tax1 and the mutants. Through this interaction, Tax1 altered the subcellular localization of Dlg from the detergent-soluble to the detergent-insoluble fraction in a fibroblast cell line as well as in HTLV-1-infected T-cell lines. These results suggest that the interaction of Tax1 with PDZ domain protein(s) is critically involved in the transforming activity of Tax1, the activity of which may be a crucial factor in malignant transformation of HTLV-1-infected cells in vivo

  19. The PDZ protein GIPC regulates trafficking of the LPA1 receptor from APPL signaling endosomes and attenuates the cell's response to LPA.

    Directory of Open Access Journals (Sweden)

    Tal Varsano

    Full Text Available Lysophosphatidic acid (LPA mediates diverse cellular responses through the activation of at least six LPA receptors--LPA(1-6, but the interacting proteins and signaling pathways that mediate the specificity of these receptors are largely unknown. We noticed that LPA(1 contains a PDZ binding motif (SVV identical to that present in two other proteins that interact with the PDZ protein GIPC. GIPC is involved in endocytic trafficking of several receptors including TrkA, VEGFR2, lutropin and dopamine D2 receptors. Here we show that GIPC binds directly to the PDZ binding motif of LPA(1 but not that of other LPA receptors. LPA(1 colocalizes and coimmunoprecipitates with GIPC and its binding partner APPL, an activator of Akt signaling found on APPL signaling endosomes. GIPC depletion by siRNA disturbed trafficking of LPA(1 to EEA1 early endosomes and promoted LPA(1 mediated Akt signaling, cell proliferation, and cell motility. We propose that GIPC binds LPA(1 and promotes its trafficking from APPL-containing signaling endosomes to EEA1 early endosomes and thus attenuates LPA-mediated Akt signaling from APPL endosomes.

  20. PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo.

    Science.gov (United States)

    Xie, Li; Yamamoto, Brenda; Haoudi, Abdelali; Semmes, O John; Green, Patrick L

    2006-03-01

    HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1deltaPBM, HTLV-2+C22(+PBM), and HTLV-2+ C18(deltaPBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFkappaB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1- and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1deltaPBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo.

  1. Characterization of big bang, a novel gene encoding for PDZ domain-containing proteins that are dynamically expressed throughout Drosophila development.

    Science.gov (United States)

    Kim, Sabrina Y; Renihan, Maia K; Boulianne, Gabrielle L

    2006-06-01

    PDZ (PSD-95, Discs-large, ZO-1) domain proteins often function as scaffolding proteins and have been shown to play important roles in diverse cellular processes such as the establishment and maintenance of cell polarity, and signal transduction. Here, we report the identification and cloning of a novel Drosophila melanogaster gene that is predicted to produce several different PDZ domain-containing proteins through alternative promoter usage and alternative splicing. This gene, that we have named big bang (bbg), was first identified as C96-GAL4, a GAL4 enhancer trap line that was generated in our lab. To further characterize bbg, its expression pattern was examined in ovaries, embryos, and late third instar larvae using UAS reporter gene constructs, in situ hybridization, or immunocytochemistry. In addition, the expression of alternatively spliced transcripts was examined in more detail using in situ hybridization. We find that during embryogenesis bbg is predominantly expressed in the developing gut, but it is also expressed in external sensory organs found in the epidermis. In the late third instar larva, bbg is expressed along the presumptive wing margin in the wing disc, broadly in the eye disc, and in other imaginal discs as well as in the brain. The expression patterns observed are dynamic and specific during development, suggesting that like other genes that encode for several different PDZ domain protein isoforms, bbg likely plays important roles in multiple developmental processes.

  2. The PDZ motif of the α1C subunit is not required for surface trafficking and adrenergic modulation of CaV1.2 channel in the heart.

    Science.gov (United States)

    Yang, Lin; Katchman, Alexander; Weinberg, Richard L; Abrams, Jeffrey; Samad, Tahmina; Wan, Elaine; Pitt, Geoffrey S; Marx, Steven O

    2015-01-23

    Voltage-gated Ca(2+) channels play a key role in initiating muscle excitation-contraction coupling, neurotransmitter release, gene expression, and hormone secretion. The association of CaV1.2 with a supramolecular complex impacts trafficking, localization, turnover, and, most importantly, multifaceted regulation of its function in the heart. Several studies hint at an important role for the C terminus of the α1C subunit as a hub for multidimensional regulation of CaV1.2 channel trafficking and function. Recent studies have demonstrated an important role for the four-residue PDZ binding motif at the C terminus of α1C in interacting with scaffold proteins containing PDZ domains, in the subcellular localization of CaV1.2 in neurons, and in the efficient signaling to cAMP-response element-binding protein in neurons. However, the role of the α1C PDZ ligand domain in the heart is not known. To determine whether the α1C PDZ motif is critical for CaV1.2 trafficking and function in cardiomyocytes, we generated transgenic mice with inducible expression of an N-terminal FLAG epitope-tagged dihydropyridine-resistant α1C with the PDZ motif deleted (ΔPDZ). These mice were crossed with α-myosin heavy chain reverse transcriptional transactivator transgenic mice, and the double-transgenic mice were fed doxycycline. The ΔPDZ channels expressed, trafficked to the membrane, and supported robust excitation-contraction coupling in the presence of nisoldipine, a dihydropyridine Ca(2+) channel blocker, providing functional evidence that they appropriately target to dyads. The ΔPDZ Ca(2+) channels were appropriately regulated by isoproterenol and forskolin. These data indicate that the α1C PDZ motif is not required for surface trafficking, localization to the dyad, or adrenergic stimulation of CaV1.2 in adult cardiomyocytes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.

    Science.gov (United States)

    Kanamori, Mutsumi; Sandy, Peter; Marzinotto, Stefania; Benetti, Roberta; Kai, Chikatoshi; Hayashizaki, Yoshihide; Schneider, Claudio; Suzuki, Harukazu

    2003-10-03

    Wnt signaling is essential during development while deregulation of this pathway frequently leads to the formation of various tumors including colorectal carcinomas. A key component of the pathway is beta-catenin that, in association with TCF-4, directly regulates the expression of Wnt-responsive genes. To identify novel binding partners of beta-catenin that may control its transcriptional activity, we performed a mammalian two-hybrid screen and isolated the Tax-interacting protein (TIP-1). The in vivo complex formation between beta-catenin and TIP-1 was verified by coimmunoprecipitation, and a direct physical association was revealed by glutathione S-transferase pull-down experiments in vitro. By using a panel of deletion mutants of both proteins, we demonstrate that the interaction is mediated by the PDZ (PSD-95/DLG/ZO-1 homology) domain of TIP-1 and requires primarily the last four amino acids of beta-catenin. TIP-1 overexpression resulted in a dose-dependent decrease in the transcriptional activity of beta-catenin when tested on the TOP/FOPFLASH reporter system. Conversely, siRNA-mediated knock-down of endogenous TIP-1 slightly increased endogenous beta-catenin transactivation function. Moreover, we show that overexpression of TIP-1 reduced the proliferation and anchorage-independent growth of colorectal cancer cells. These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway.

  4. Serine 77 in the PDZ domain of PICK1 is a protein kinase Cα phosphorylation site regulated by lipid membrane binding

    DEFF Research Database (Denmark)

    Ammendrup-Johnsen, Ina; Thorsen, Thor Seneca; Gether, Ulrik

    2012-01-01

    PICK1 (protein interacting with C kinase 1) contains an N-terminal protein binding PDZ domain and a C-terminal lipid binding BAR domain. PICK1 plays a key role in several physiological processes, including synaptic plasticity. However, little is known about the cellular mechanisms governing the a...... lipid binding and/or polymerization capacity. We propose that PICK1 is phosphorylated at Ser77 by PKCα preferentially when bound to membrane vesicles and that this phosphorylation in turn modulates its cellular distribution....

  5. The expression of the new epididymal luminal protein of PDZ domain containing 1 is decreased in asthenozoospermia

    Directory of Open Access Journals (Sweden)

    A-Juan Liang

    2018-01-01

    Full Text Available Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ. Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1, also named Na+/H+ exchange regulatory cofactor 3 (NHERF3, which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.

  6. Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein

    Science.gov (United States)

    Marsh, Elizabeth K.; Delury, Craig P.; Davies, Nicholas J.; Weston, Christopher J.; Miah, Mohammed A.L.; Banks, Lawrence; Parish, Joanna L.

    2017-01-01

    The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification. PMID:28061478

  7. Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.

    Science.gov (United States)

    Marsh, Elizabeth K; Delury, Craig P; Davies, Nicholas J; Weston, Christopher J; Miah, Mohammed A L; Banks, Lawrence; Parish, Joanna L; Higgs, Martin R; Roberts, Sally

    2017-03-21

    The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification.

  8. In vitro and in vivo Analysis of the Binding of the C Terminus of the HDL Receptor Scavenger Receptor Class B type I (SR-BI) to the PDZ1 Domain of its Cytoplasmic Adaptor Protein PDZK1

    Energy Technology Data Exchange (ETDEWEB)

    O Kocher; G Birrane; K Tsukamoto; S Fenske; A Yesilaltay; R Pal; K Daniels; J Ladias; M Krieger

    2011-12-31

    The PDZ1 domain of the four PDZ domain-containing protein PDZK1 has been reported to bind the C terminus of the HDL receptor scavenger receptor class B, type I (SR-BI), and to control hepatic SR-BI expression and function. We generated wild-type (WT) and mutant murine PDZ1 domains, the mutants bearing single amino acid substitutions in their carboxylate binding loop (Lys(14)-Xaa(4)-Asn(19)-Tyr-Gly-Phe-Phe-Leu(24)), and measured their binding affinity for a 7-residue peptide corresponding to the C terminus of SR-BI ((503)VLQEAKL(509)). The Y20A and G21Y substitutions abrogated all binding activity. Surprisingly, binding affinities (K(d)) of the K14A and F22A mutants were 3.2 and 4.0 ?M, respectively, similar to 2.6 ?M measured for the WT PDZ1. To understand these findings, we determined the high resolution structure of WT PDZ1 bound to a 5-residue sequence from the C-terminal SR-BI ((505)QEAKL(509)) using x-ray crystallography. In addition, we incorporated the K14A and Y20A substitutions into full-length PDZK1 liver-specific transgenes and expressed them in WT and PDZK1 knock-out mice. In WT mice, the transgenes did not alter endogenous hepatic SR-BI protein expression (intracellular distribution or amount) or lipoprotein metabolism (total plasma cholesterol, lipoprotein size distribution). In PDZK1 knock-out mice, as expected, the K14A mutant behaved like wild-type PDZK1 and completely corrected their hepatic SR-BI and plasma lipoprotein abnormalities. Unexpectedly, the 10-20-fold overexpressed Y20A mutant also substantially, but not completely, corrected these abnormalities. The results suggest that there may be an additional site(s) within PDZK1 that bind(s) SR-BI and mediate(s) productive SR-BI-PDZK1 interaction previously attributed exclusively to the canonical binding of the C-terminal SR-BI to PDZ1.

  9. Two barcodes encoded by the type-1 PDZ and by phospho-Ser312 regulate retromer/WASH-mediated sorting of the ß1-adrenergic receptor from endosomes to the plasma membrane.

    Science.gov (United States)

    Nooh, Mohammed M; Bahouth, Suleiman W

    2017-01-01

    Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß 1 -AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß 1 -AR is inhibited when PKA or its substrate serine at position 312 (Ser 312 ) are inactivated. We tested the hypothesis that phospho-Ser 312 provided a second barcode for ß 1 -AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß 1 -AR trafficking. Recycling of WT ß 1 -AR or WT ß 2 -AR was dependent on targeting the retromer to endosomal membranes via SNX3 and rab7a, and on complexing the retromer to the WASH pentamer via the C-tail of FAM21 (FAM21 C ). These maneuvers however, did not inhibit the recycling of a phospho-Ser 312 ß 1 -AR mimic ((S312D) ß 1 -AR). Knockdown of the trans-acting PDZ protein sorting nexin27 (SNX27) inhibited the recycling of WT ß 1 -AR and WT ß 2 -AR, but had no effect on (S312D) ß 1 -AR∆PDZ or on phosphorylation of WT ß 1 -AR by PKA at Ser 312 . However, depletion of FKBP15, a FAM21 C -binding endosomal protein, selectively inhibited WT ß 1 -AR but not ß 2 -AR recycling, suggesting divergence might exist in GPCR trafficking roadmaps. These results indicate that two barcodes are involved in sorting WT ß 1 -AR out of early endosomes. The first and antecedent "barcode" was the "type-1 PDZ", followed by a second reversible "phospho-Ser 312 " verification "barcode". This organization allows tight regulation of ß 1 -AR density to signaling intensity in conditions associated with aberrant ß 1 -AR signaling such as in hypertension and heart failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Directory of Open Access Journals (Sweden)

    Aniko Keller-Pinter

    Full Text Available The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs. Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu mutant of syndecan-4 (SDC4. SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1 to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  11. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction–dependent manner

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1–RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways. PMID:29121646

  12. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef; Szilak, Laszlo

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  13. The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells.

    Science.gov (United States)

    Zou, Junhuang; Chen, Qian; Almishaal, Ali; Mathur, Pranav Dinesh; Zheng, Tihua; Tian, Cong; Zheng, Qing Y; Yang, Jun

    2017-02-01

    Usher syndrome (USH) is the most common cause of inherited deaf-blindness, manifested as USH1, USH2 and USH3 clinical types. The protein products of USH2 causative and modifier genes, USH2A, ADGRV1, WHRN and PDZD7, interact to assemble a multiprotein complex at the ankle link region of the mechanosensitive stereociliary bundle in hair cells. Defects in this complex cause stereociliary bundle disorganization and hearing loss. The four USH2 proteins also interact in vitro with USH1 proteins including myosin VIIa, USH1G (SANS), CIB2 and harmonin. However, it is unclear whether the interactions between USH1 and USH2 proteins occur in vivo and whether USH1 proteins play a role in USH2 complex assembly in hair cells. In this study, we identified a novel interaction between myosin VIIa and PDZD7 by FLAG pull-down assay. We further investigated the role of the above-mentioned four USH1 proteins in the cochlear USH2 complex assembly using USH1 mutant mice. We showed that only myosin VIIa is indispensable for USH2 complex assembly at ankle links, indicating the potential transport and/or anchoring role of myosin VIIa for USH2 proteins in hair cells. However, myosin VIIa is not required for USH2 complex assembly in photoreceptors. We further showed that, while PDZ protein harmonin is not involved, its paralogous USH2 proteins, PDZD7 and whirlin, function synergistically in USH2 complex assembly in cochlear hair cells. In summary, our studies provide novel insight into the functional relationship between USH1 and USH2 proteins in the cochlea and the retina as well as the disease mechanisms underlying USH1 and USH2. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Confinement of β1- and β2-adrenergic receptors in the plasma membrane of cardiomyocyte-like H9c2 cells is mediated by selective interactions with PDZ domain and A-kinase anchoring proteins but not caveolae

    Science.gov (United States)

    Valentine, Cathleen D.; Haggie, Peter M.

    2011-01-01

    The sympathetic nervous system regulates cardiac output by activating adrenergic receptors (ARs) in cardiac myocytes. The predominant cardiac ARs, β1- and β2AR, are structurally similar but mediate distinct signaling responses. Scaffold protein–mediated compartmentalization of ARs into discrete, multiprotein complexes has been proposed to dictate differential signaling responses. To test the hypothesis that βARs integrate into complexes in live cells, we measured receptor diffusion and interactions by single-particle tracking. Unstimulated β1- and β2AR were highly confined in the membrane of H9c2 cardiomyocyte-like cells, indicating that receptors are tethered and presumably integrated into protein complexes. Selective disruption of interactions with postsynaptic density protein 95/disks large/zonula occludens-1 (PDZ)–domain proteins and A-kinase anchoring proteins (AKAPs) increased receptor diffusion, indicating that these scaffold proteins participate in receptor confinement. In contrast, modulation of interactions between the putative scaffold caveolae and β2AR did not alter receptor dynamics, suggesting that these membrane domains are not involved in β2AR confinement. For both β1- and β2AR, the receptor carboxy-terminus was uniquely responsible for scaffold interactions. Our data formally demonstrate that distinct and stable protein complexes containing β1- or β2AR are formed in the plasma membrane of cardiomyocyte-like cells and that selective PDZ and AKAP interactions are responsible for the integration of receptors into complexes. PMID:21680711

  15. Confinement of β(1)- and β(2)-adrenergic receptors in the plasma membrane of cardiomyocyte-like H9c2 cells is mediated by selective interactions with PDZ domain and A-kinase anchoring proteins but not caveolae.

    Science.gov (United States)

    Valentine, Cathleen D; Haggie, Peter M

    2011-08-15

    The sympathetic nervous system regulates cardiac output by activating adrenergic receptors (ARs) in cardiac myocytes. The predominant cardiac ARs, β(1)- and β(2)AR, are structurally similar but mediate distinct signaling responses. Scaffold protein-mediated compartmentalization of ARs into discrete, multiprotein complexes has been proposed to dictate differential signaling responses. To test the hypothesis that βARs integrate into complexes in live cells, we measured receptor diffusion and interactions by single-particle tracking. Unstimulated β(1)- and β(2)AR were highly confined in the membrane of H9c2 cardiomyocyte-like cells, indicating that receptors are tethered and presumably integrated into protein complexes. Selective disruption of interactions with postsynaptic density protein 95/disks large/zonula occludens-1 (PDZ)-domain proteins and A-kinase anchoring proteins (AKAPs) increased receptor diffusion, indicating that these scaffold proteins participate in receptor confinement. In contrast, modulation of interactions between the putative scaffold caveolae and β(2)AR did not alter receptor dynamics, suggesting that these membrane domains are not involved in β(2)AR confinement. For both β(1)- and β(2)AR, the receptor carboxy-terminus was uniquely responsible for scaffold interactions. Our data formally demonstrate that distinct and stable protein complexes containing β(1)- or β(2)AR are formed in the plasma membrane of cardiomyocyte-like cells and that selective PDZ and AKAP interactions are responsible for the integration of receptors into complexes.

  16. The PDZ domain binding motif (PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation.

    Science.gov (United States)

    Aoyagi, Tomoya; Takahashi, Masahiko; Higuchi, Masaya; Oie, Masayasu; Tanaka, Yuetsu; Kiyono, Tohru; Aoyagi, Yutaka; Fujii, Masahiro

    2010-04-01

    Several tumor viruses, such as human T-cell leukemia virus (HTLV), human papilloma virus (HPV), human adenovirus, have high-oncogenic and low-oncogenic subtypes, and such subtype-specific oncogenesis is associated with the PDZ-domain binding motif (PBM) in their transforming proteins. HTLV-1, the causative agent of adult T-cell leukemia, encodes Tax1 with PBM as a transforming protein. The Tax1 PBM was substituted with those from other oncoviruses, and the transforming activity was examined. Tax1 mutants with PBM from either HPV-16 E6 or adenovirus type 9 E4ORF1 are fully active in the transformation of a mouse T-cell line from interleukin-2-dependent growth into independent growth. Interestingly, one such Tax1 PBM mutant had an extra amino acid insertion derived from E6 between PBM and the rest of Tax1, thus suggesting that the amino acid sequences of the peptides between PBM and the rest of Tax1 and the numbers only slightly affect the function of PBM in the transformation. Tax1 and Tax1 PBM mutants interacted with tumor suppressors Dlg1 and Scribble with PDZ-domains. Unlike E6, Tax1 PBM mutants as well as Tax1 did not or minimally induced the degradations of Dlg1 and Scribble, but instead induced their subcellular translocation from the detergent-soluble fraction into the insoluble fraction, thus suggesting that the inactivation mechanism of these tumor suppressor proteins is distinct. The present results suggest that PBMs of high-risk oncoviruses have a common function(s) required for these three tumor viruses to transform cells, which is likely associated with the subtype-specific oncogenesis of these tumor viruses.

  17. Optimization and Optimal Control

    CERN Document Server

    Chinchuluun, Altannar; Enkhbat, Rentsen; Tseveendorj, Ider

    2010-01-01

    During the last four decades there has been a remarkable development in optimization and optimal control. Due to its wide variety of applications, many scientists and researchers have paid attention to fields of optimization and optimal control. A huge number of new theoretical, algorithmic, and computational results have been observed in the last few years. This book gives the latest advances, and due to the rapid development of these fields, there are no other recent publications on the same topics. Key features: Provides a collection of selected contributions giving a state-of-the-art accou

  18. Optimally Stopped Optimization

    Science.gov (United States)

    Vinci, Walter; Lidar, Daniel

    We combine the fields of heuristic optimization and optimal stopping. We propose a strategy for benchmarking randomized optimization algorithms that minimizes the expected total cost for obtaining a good solution with an optimal number of calls to the solver. To do so, rather than letting the objective function alone define a cost to be minimized, we introduce a further cost-per-call of the algorithm. We show that this problem can be formulated using optimal stopping theory. The expected cost is a flexible figure of merit for benchmarking probabilistic solvers that can be computed when the optimal solution is not known, and that avoids the biases and arbitrariness that affect other measures. The optimal stopping formulation of benchmarking directly leads to a real-time, optimal-utilization strategy for probabilistic optimizers with practical impact. We apply our formulation to benchmark the performance of a D-Wave 2X quantum annealer and the HFS solver, a specialized classical heuristic algorithm designed for low tree-width graphs. On a set of frustrated-loop instances with planted solutions defined on up to N = 1098 variables, the D-Wave device is between one to two orders of magnitude faster than the HFS solver.

  19. Human T-Cell Leukemia Virus Type I-Mediated Repression of PDZ-LIM Domain-Containing Protein 2 Involves DNA Methylation But Independent of the Viral Oncoprotein Tax

    Directory of Open Access Journals (Sweden)

    Pengrong Yan

    2009-10-01

    Full Text Available Human T-cell leukemia virus type I (HTLV-I is the etiological agent of adult T-cell leukemia (ATL. Our recent studies have shown that one important mechanism of HTLV-I-Mediated tumorigenesis is through PDZ-LIM domain-containing protein 2 (PDLIM2 repression, although the involved mechanism remains unknown. Here, we further report that HTLV-I-Mediated PDLIM2 repression was a pathophysiological event and the PDLIM2 repression involved DNA methylation. Whereas DNA methyltransferases 1 and 3b but not 3a were upregulated in HTLV-I-transformed T cells, the hypomethylating agent 5-aza-2′-deoxycytidine (5-aza-dC restored PDLIM2 expression and induced death of these malignant cells. Notably, the PDLIM2 repression was independent of the viral regulatory protein Tax because neither short-term induction nor long-term stable expression of Tax could downregulate PDLIM2 expression. These studies provide important insights into PDLIM2 regulation, HTLV-I leukemogenicity, long latency, and cancer health disparities. Given the efficient antitumor activity with no obvious toxicity of 5-aza-dC, these studies also suggest potential therapeutic strategies for ATL.

  20. The PDZ and band 4.1 containing protein Frmpd1 regulates the subcellular location of activator of G-protein signaling 3 and its interaction with G-proteins.

    Science.gov (United States)

    An, Ningfei; Blumer, Joe B; Bernard, Michael L; Lanier, Stephen M

    2008-09-05

    Activator of G-protein signaling 3 (AGS3) is one of nine mammalian proteins containing one or more G-protein regulatory (GPR) motifs that stabilize the GDP-bound conformation of Galphai. Such proteins have revealed unexpected functional diversity for the "G-switch" in the control of events within the cell independent of the role of heterotrimeric G-proteins as transducers for G-protein-coupled receptors at the cell surface. A key question regarding this class of proteins is what controls their subcellular positioning and interaction with G-proteins. We conducted a series of yeast two-hybrid screens to identify proteins interacting with the tetratricopeptide repeat (TPR) of AGS3, which plays an important role in subcellular positioning of the protein. We report the identification of Frmpd1 (FERM and PDZ domain containing 1) as a regulatory binding partner of AGS3. Frmpd1 binds to the TPR domain of AGS3 and coimmunoprecipitates with AGS3 from cell lysates. Cell fractionation indicated that Frmpd1 stabilizes AGS3 in a membrane fraction. Upon cotransfection of COS7 cells with Frmpd1-GFP and AGS3-mRFP, AGS3-mRFP is observed in regions of the cell cortex and also in membrane extensions or processes where it appears to be colocalized with Frmpd1-GFP based upon the merged fluorescent signals. Frmpd1 knockdown (siRNA) in Cath.a-differentiated neuronal cells decreased the level of endogenous AGS3 in membrane fractions by approximately 50% and enhanced the alpha2-adrenergic receptor-mediated inhibition of forskolin-induced increases in cAMP. The coimmunoprecipitation of Frmpd1 with AGS3 is lost as the amount of Galphai3 in the cell is increased and AGS3 apparently switches its binding partner from Frmpd1 to Galphai3 indicating that the interaction of AGS3 with Frmpd1 and Galphai3 is mutually exclusive. Mechanistically, Frmpd1 may position AGS3 in a membrane environment where it then interacts with Galphai in a regulated manner.

  1. Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer.

    Science.gov (United States)

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Luzzati, Alessandro; Perrucchini, Giuseppe; Desiderio, Maria Alfonsina

    2013-07-01

    The hypoxic microenvironment of bone marrow favours the bone metastasis process. Hypoxia inducible factor (HIF)-1α is hallmark for hypoxia, correlating with poor prognosis and radio/chemotherapy resistance of primary-breast carcinoma. For bone metastasis, the molecular mechanisms involved in HIF-1α expression and HIF-1 (α/β heterodimer)-transcription factor activity are scarcely known. We studied the role played by HIF-1 in the cross-talk between neoplastic and supportive-microenvironmental cells. Also, WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ) were taken into consideration evaluating whether these Hippo-pathway effectors affect bone-metastatic phenotype through HIF-1 activity. Considering bone-metastasis specimens, nuclear HIF-1α-TAZ co-localisation occurred in neoplastic and supportive cells, such as fibroblasts and endotheliocytes. Based on these data, the functional importance was verified using 1833-bone metastatic clone under hypoxia: nuclear HIF-1α and TAZ expression increased and co-immunoprecipitated, activating HIF-1-DNA binding and transactivation. In contrast, Wwox localised at perinuclear level in neoplastic cells of bone metastasis, being almost absent in supportive cells, and Wwox-protein expression diminished in hypoxic-1833 cells. Thus, TAZ regulation of HIF-1 activity might be important for bone-secondary growth, participating in metastasis-stroma cross-talk. Further, TAZ and HIF-1α-protein levels seemed correlated. In fact, blocking cyclooxygenase-2 with NS398 in hypoxic-1833 cells, not only HIF-1α decreased but also molecular-mechanism(s) upstream of the Hippo pathway were triggered: LATS-dependent TAZ phosphorylation seemed responsible for TAZ nucleus/cytoplasm translocation and degradation. In the 1833-xenograft model, NS398 largely prevented the outgrowth of bone-metastatic cells, probably related to remarkable-extracellular matrix assembly. We gained clinical insight into

  2. Nonlinear optimization

    CERN Document Server

    Ruszczynski, Andrzej

    2011-01-01

    Optimization is one of the most important areas of modern applied mathematics, with applications in fields from engineering and economics to finance, statistics, management science, and medicine. While many books have addressed its various aspects, Nonlinear Optimization is the first comprehensive treatment that will allow graduate students and researchers to understand its modern ideas, principles, and methods within a reasonable time, but without sacrificing mathematical precision. Andrzej Ruszczynski, a leading expert in the optimization of nonlinear stochastic systems, integrates the theory and the methods of nonlinear optimization in a unified, clear, and mathematically rigorous fashion, with detailed and easy-to-follow proofs illustrated by numerous examples and figures. The book covers convex analysis, the theory of optimality conditions, duality theory, and numerical methods for solving unconstrained and constrained optimization problems. It addresses not only classical material but also modern top...

  3. Website Optimization

    CERN Document Server

    King, Andrew

    2008-01-01

    Remember when an optimized website was one that merely didn't take all day to appear? Times have changed. Today, website optimization can spell the difference between enterprise success and failure, and it takes a lot more know-how to achieve success. This book is a comprehensive guide to the tips, techniques, secrets, standards, and methods of website optimization. From increasing site traffic to maximizing leads, from revving up responsiveness to increasing navigability, from prospect retention to closing more sales, the world of 21st century website optimization is explored, exemplified a

  4. Optimality Conditions in Vector Optimization

    CERN Document Server

    Jiménez, Manuel Arana; Lizana, Antonio Rufián

    2011-01-01

    Vector optimization is continuously needed in several science fields, particularly in economy, business, engineering, physics and mathematics. The evolution of these fields depends, in part, on the improvements in vector optimization in mathematical programming. The aim of this Ebook is to present the latest developments in vector optimization. The contributions have been written by some of the most eminent researchers in this field of mathematical programming. The Ebook is considered essential for researchers and students in this field.

  5. Medicinsk Optimering

    DEFF Research Database (Denmark)

    Birkholm, Klavs

    2010-01-01

    En undersøgelse af anvendelsen af medicin til optimering af koncentration, hukommelse og følelsestonus. Efterfulgt af etiske overvejelser og anbefalinger til det politiske system......En undersøgelse af anvendelsen af medicin til optimering af koncentration, hukommelse og følelsestonus. Efterfulgt af etiske overvejelser og anbefalinger til det politiske system...

  6. Structural optimization

    CERN Document Server

    MacBain, Keith M

    2009-01-01

    Intends to supplement the engineer's box of analysis and design tools making optimization as commonplace as the finite element method in the engineering workplace. This title introduces structural optimization and the methods of nonlinear programming such as Lagrange multipliers, Kuhn-Tucker conditions, and calculus of variations.

  7. Topology Optimization

    DEFF Research Database (Denmark)

    A. Kristensen, Anders Schmidt; Damkilde, Lars

    2007-01-01

    . A way to solve the initial design problem namely finding a form can be solved by so-called topology optimization. The idea is to define a design region and an amount of material. The loads and supports are also fidefined, and the algorithm finds the optimal material distribution. The objective function...... dictates the form, and the designer can choose e.g. maximum stiness, maximum allowable stresses or maximum lowest eigenfrequency. The result of the topology optimization is a relatively coarse map of material layout. This design can be transferred to a CAD system and given the necessary geometrically...... refinements, and then remeshed and reanalysed in other to secure that the design requirements are met correctly. The output of standard topology optimization has seldom well-defined, sharp contours leaving the designer with a tedious interpretation, which often results in less optimal structures. In the paper...

  8. Dispositional Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.

    2014-01-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. PMID:24630971

  9. Portfolio Optimization

    OpenAIRE

    Issagali, Aizhan; Alshimbayeva, Damira; Zhalgas, Aidana

    2015-01-01

    In this paper Portfolio Optimization techniques were used to determine the most favorable investment portfolio. In particular, stock indices of three companies, namely Microsoft Corporation, Christian Dior Fashion House and Shevron Corporation were evaluated. Using this data the amounts invested in each asset when a portfolio is chosen on the efficient frontier were calculated. In addition, the Portfolio with minimum variance, tangency portfolio and optimal Markowitz portfolio are presented.

  10. Radiological optimization

    International Nuclear Information System (INIS)

    Zeevaert, T.

    1998-01-01

    Radiological optimization is one of the basic principles in each radiation-protection system and it is a basic requirement in the safety standards for radiation protection in the European Communities. The objectives of the research, performed in this field at the Belgian Nuclear Research Centre SCK-CEN, are: (1) to implement the ALARA principles in activities with radiological consequences; (2) to develop methodologies for optimization techniques in decision-aiding; (3) to optimize radiological assessment models by validation and intercomparison; (4) to improve methods to assess in real time the radiological hazards in the environment in case of an accident; (5) to develop methods and programmes to assist decision-makers during a nuclear emergency; (6) to support the policy of radioactive waste management authorities in the field of radiation protection; (7) to investigate existing software programmes in the domain of multi criteria analysis. The main achievements for 1997 are given

  11. Optimizing detectability

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    HPLC is useful for trace and ultratrace analyses of a variety of compounds. For most applications, HPLC is useful for determinations in the nanogram-to-microgram range; however, detection limits of a picogram or less have been demonstrated in certain cases. These determinations require state-of-the-art capability; several examples of such determinations are provided in this chapter. As mentioned before, to detect and/or analyze low quantities of a given analyte at submicrogram or ultratrace levels, it is necessary to optimize the whole separation system, including the quantity and type of sample, sample preparation, HPLC equipment, chromatographic conditions (including column), choice of detector, and quantitation techniques. A limited discussion is provided here for optimization based on theoretical considerations, chromatographic conditions, detector selection, and miscellaneous approaches to detectability optimization. 59 refs

  12. Unconstrained Optimization

    DEFF Research Database (Denmark)

    Frandsen, P. E.; Jonasson, K.; Nielsen, Hans Bruun

    1999-01-01

    This lecture note is intended for use in the course 04212 Optimization and Data Fitting at the Technincal University of Denmark. It covers about 25% of the curriculum. Hopefully, the note may be useful also to interested persons not participating in that course. The aim of the note is to give...... an introduction to algorithms for unconstrained optimization. We present Conjugate Gradient, Damped Newton and Quasi Newton methods together with the relevant theoretical background. The reader is assumed to be familiar with algorithms for solving linear and nonlinear system of equations, at a level corresponding...

  13. Optimal transport

    CERN Document Server

    Eckmann, B

    2008-01-01

    At the close of the 1980s, the independent contributions of Yann Brenier, Mike Cullen and John Mather launched a revolution in the venerable field of optimal transport founded by G Monge in the 18th century, which has made breathtaking forays into various other domains of mathematics ever since. The author presents a broad overview of this area.

  14. Topology optimization

    DEFF Research Database (Denmark)

    Bendsøe, Martin P.; Sigmund, Ole

    2007-01-01

    Taking as a starting point a design case for a compliant mechanism (a force inverter), the fundamental elements of topology optimization are described. The basis for the developments is a FEM format for this design problem and emphasis is given to the parameterization of design as a raster image...

  15. Optimal control

    CERN Document Server

    Aschepkov, Leonid T; Kim, Taekyun; Agarwal, Ravi P

    2016-01-01

    This book is based on lectures from a one-year course at the Far Eastern Federal University (Vladivostok, Russia) as well as on workshops on optimal control offered to students at various mathematical departments at the university level. The main themes of the theory of linear and nonlinear systems are considered, including the basic problem of establishing the necessary and sufficient conditions of optimal processes. In the first part of the course, the theory of linear control systems is constructed on the basis of the separation theorem and the concept of a reachability set. The authors prove the closure of a reachability set in the class of piecewise continuous controls, and the problems of controllability, observability, identification, performance and terminal control are also considered. The second part of the course is devoted to nonlinear control systems. Using the method of variations and the Lagrange multipliers rule of nonlinear problems, the authors prove the Pontryagin maximum principle for prob...

  16. Discrete optimization

    CERN Document Server

    Parker, R Gary

    1988-01-01

    This book treats the fundamental issues and algorithmic strategies emerging as the core of the discipline of discrete optimization in a comprehensive and rigorous fashion. Following an introductory chapter on computational complexity, the basic algorithmic results for the two major models of polynomial algorithms are introduced--models using matroids and linear programming. Further chapters treat the major non-polynomial algorithms: branch-and-bound and cutting planes. The text concludes with a chapter on heuristic algorithms.Several appendixes are included which review the fundamental ideas o

  17. [SIAM conference on optimization

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-10

    Abstracts are presented of 63 papers on the following topics: large-scale optimization, interior-point methods, algorithms for optimization, problems in control, network optimization methods, and parallel algorithms for optimization problems.

  18. Optimization modeling with spreadsheets

    CERN Document Server

    Baker, Kenneth R

    2015-01-01

    An accessible introduction to optimization analysis using spreadsheets Updated and revised, Optimization Modeling with Spreadsheets, Third Edition emphasizes model building skills in optimization analysis. By emphasizing both spreadsheet modeling and optimization tools in the freely available Microsoft® Office Excel® Solver, the book illustrates how to find solutions to real-world optimization problems without needing additional specialized software. The Third Edition includes many practical applications of optimization models as well as a systematic framework that il

  19. Observability Analysis of DVL/PS Aided INS for a Maneuvering AUV

    Directory of Open Access Journals (Sweden)

    Itzik Klein

    2015-10-01

    Full Text Available Recently, ocean exploration has increased considerably through the use of autonomous underwater vehicles (AUV. A key enabling technology is the precision of the AUV navigation capability. In this paper, we focus on understanding the limitation of the AUV navigation system. That is, what are the observable error-states for different maneuvering types of the AUV? Since analyzing the performance of an underwater navigation system is highly complex, to answer the above question, current approaches use simulations. This, of course, limits the conclusions to the emulated type of vehicle used and to the simulation setup. For this reason, we take a different approach and analyze the system observability for different types of vehicle dynamics by finding the set of observable and unobservable states. To that end, we apply the observability Gramian approach, previously used only for terrestrial applications. We demonstrate our analysis for an underwater inertial navigation system aided by a Doppler velocity logger or by a pressure sensor. The result is a first prediction of the performance of an AUV standing, rotating at a position and turning at a constant speed. Our conclusions of the observable and unobservable navigation error states for different dynamics are supported by extensive numerical simulation.

  20. Optimal Pollution, Optimal Population, and Sustainability

    OpenAIRE

    Ulla Lehmijoki

    2012-01-01

    This paper develops a long-run consumer optimization model with endogenous pollution and endogenous population. The positive check increases mortality if pollution increases. The optimal path is sustainable if it provides non-decreasing consumption for a non-decreasing population. As usually, optimality and sustainability may conflict; with population endogenous to pollution, this conflict may ultimately lead the human species toward self-imposed extinction. Not even technical progress can wa...

  1. Applications of combinatorial optimization

    CERN Document Server

    Paschos, Vangelis Th

    2013-01-01

    Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management. The three volumes of the Combinatorial Optimization series aims to cover a wide range of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization. "Applications of Combinatorial Optimization" is presenting a certain number among the most common and well-known applications of Combinatorial Optimization.

  2. Global Optimization using Interval Analysis : Interval Optimization for Aerospace Applications

    NARCIS (Netherlands)

    Van Kampen, E.

    2010-01-01

    Optimization is an important element in aerospace related research. It is encountered for example in trajectory optimization problems, such as: satellite formation flying, spacecraft re-entry optimization and airport approach and departure optimization; in control optimization, for example in

  3. Mechanical Design Optimization Using Advanced Optimization Techniques

    CERN Document Server

    Rao, R Venkata

    2012-01-01

    Mechanical design includes an optimization process in which designers always consider objectives such as strength, deflection, weight, wear, corrosion, etc. depending on the requirements. However, design optimization for a complete mechanical assembly leads to a complicated objective function with a large number of design variables. It is a good practice to apply optimization techniques for individual components or intermediate assemblies than a complete assembly. Analytical or numerical methods for calculating the extreme values of a function may perform well in many practical cases, but may fail in more complex design situations. In real design problems, the number of design parameters can be very large and their influence on the value to be optimized (the goal function) can be very complicated, having nonlinear character. In these complex cases, advanced optimization algorithms offer solutions to the problems, because they find a solution near to the global optimum within reasonable time and computational ...

  4. Oil Reservoir Production Optimization using Optimal Control

    DEFF Research Database (Denmark)

    Völcker, Carsten; Jørgensen, John Bagterp; Stenby, Erling Halfdan

    2011-01-01

    Practical oil reservoir management involves solution of large-scale constrained optimal control problems. In this paper we present a numerical method for solution of large-scale constrained optimal control problems. The method is a single-shooting method that computes the gradients using the adjo...... reservoir using water ooding and smart well technology. Compared to the uncontrolled case, the optimal operation increases the Net Present Value of the oil field by 10%.......Practical oil reservoir management involves solution of large-scale constrained optimal control problems. In this paper we present a numerical method for solution of large-scale constrained optimal control problems. The method is a single-shooting method that computes the gradients using...

  5. Particle Swarm Optimization Toolbox

    Science.gov (United States)

    Grant, Michael J.

    2010-01-01

    The Particle Swarm Optimization Toolbox is a library of evolutionary optimization tools developed in the MATLAB environment. The algorithms contained in the library include a genetic algorithm (GA), a single-objective particle swarm optimizer (SOPSO), and a multi-objective particle swarm optimizer (MOPSO). Development focused on both the SOPSO and MOPSO. A GA was included mainly for comparison purposes, and the particle swarm optimizers appeared to perform better for a wide variety of optimization problems. All algorithms are capable of performing unconstrained and constrained optimization. The particle swarm optimizers are capable of performing single and multi-objective optimization. The SOPSO and MOPSO algorithms are based on swarming theory and bird-flocking patterns to search the trade space for the optimal solution or optimal trade in competing objectives. The MOPSO generates Pareto fronts for objectives that are in competition. A GA, based on Darwin evolutionary theory, is also included in the library. The GA consists of individuals that form a population in the design space. The population mates to form offspring at new locations in the design space. These offspring contain traits from both of the parents. The algorithm is based on this combination of traits from parents to hopefully provide an improved solution than either of the original parents. As the algorithm progresses, individuals that hold these optimal traits will emerge as the optimal solutions. Due to the generic design of all optimization algorithms, each algorithm interfaces with a user-supplied objective function. This function serves as a "black-box" to the optimizers in which the only purpose of this function is to evaluate solutions provided by the optimizers. Hence, the user-supplied function can be numerical simulations, analytical functions, etc., since the specific detail of this function is of no concern to the optimizer. These algorithms were originally developed to support entry

  6. Euler's fluid equations: Optimal control vs optimization

    International Nuclear Information System (INIS)

    Holm, Darryl D.

    2009-01-01

    An optimization method used in image-processing (metamorphosis) is found to imply Euler's equations for incompressible flow of an inviscid fluid, without requiring that the Lagrangian particle labels exactly follow the flow lines of the Eulerian velocity vector field. Thus, an optimal control problem and an optimization problem for incompressible ideal fluid flow both yield the same Euler fluid equations, although their Lagrangian parcel dynamics are different. This is a result of the gauge freedom in the definition of the fluid pressure for an incompressible flow, in combination with the symmetry of fluid dynamics under relabeling of their Lagrangian coordinates. Similar ideas are also illustrated for SO(N) rigid body motion.

  7. Load flow optimization and optimal power flow

    CERN Document Server

    Das, J C

    2017-01-01

    This book discusses the major aspects of load flow, optimization, optimal load flow, and culminates in modern heuristic optimization techniques and evolutionary programming. In the deregulated environment, the economic provision of electrical power to consumers requires knowledge of maintaining a certain power quality and load flow. Many case studies and practical examples are included to emphasize real-world applications. The problems at the end of each chapter can be solved by hand calculations without having to use computer software. The appendices are devoted to calculations of line and cable constants, and solutions to the problems are included throughout the book.

  8. Optimal Training Systems STTR

    National Research Council Canada - National Science Library

    Best, Brad; Lovett, Marsha

    2005-01-01

    .... Using an optimal model of task performance subject to human constraints may be a more efficient way to develop models of skilled human performance for use in training, especially since optimal models...

  9. Optimal Alarm Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — An optimal alarm system is simply an optimal level-crossing predictor that can be designed to elicit the fewest false alarms for a fixed detection probability. It...

  10. Optimization under Uncertainty

    KAUST Repository

    Lopez, Rafael H.

    2016-01-01

    in optimization, the so called the reliability based design. Subsequently, we present the risk optimization approach, which includes the expected costs of failure in the objective function. After that the basic description of each approach is given, the projects

  11. Pseudolinear functions and optimization

    CERN Document Server

    Mishra, Shashi Kant

    2015-01-01

    Pseudolinear Functions and Optimization is the first book to focus exclusively on pseudolinear functions, a class of generalized convex functions. It discusses the properties, characterizations, and applications of pseudolinear functions in nonlinear optimization problems.The book describes the characterizations of solution sets of various optimization problems. It examines multiobjective pseudolinear, multiobjective fractional pseudolinear, static minmax pseudolinear, and static minmax fractional pseudolinear optimization problems and their results. The authors extend these results to locally

  12. Optimization algorithms and applications

    CERN Document Server

    Arora, Rajesh Kumar

    2015-01-01

    Choose the Correct Solution Method for Your Optimization ProblemOptimization: Algorithms and Applications presents a variety of solution techniques for optimization problems, emphasizing concepts rather than rigorous mathematical details and proofs. The book covers both gradient and stochastic methods as solution techniques for unconstrained and constrained optimization problems. It discusses the conjugate gradient method, Broyden-Fletcher-Goldfarb-Shanno algorithm, Powell method, penalty function, augmented Lagrange multiplier method, sequential quadratic programming, method of feasible direc

  13. Optimization and optimal control in automotive systems

    CERN Document Server

    Kolmanovsky, Ilya; Steinbuch, Maarten; Re, Luigi

    2014-01-01

    This book demonstrates the use of the optimization techniques that are becoming essential to meet the increasing stringency and variety of requirements for automotive systems. It shows the reader how to move away from earlier  approaches, based on some degree of heuristics, to the use of  more and more common systematic methods. Even systematic methods can be developed and applied in a large number of forms so the text collects contributions from across the theory, methods and real-world automotive applications of optimization. Greater fuel economy, significant reductions in permissible emissions, new drivability requirements and the generally increasing complexity of automotive systems are among the criteria that the contributing authors set themselves to meet. In many cases multiple and often conflicting requirements give rise to multi-objective constrained optimization problems which are also considered. Some of these problems fall into the domain of the traditional multi-disciplinary optimization applie...

  14. Methods of mathematical optimization

    Science.gov (United States)

    Vanderplaats, G. N.

    The fundamental principles of numerical optimization methods are reviewed, with an emphasis on potential engineering applications. The basic optimization process is described; unconstrained and constrained minimization problems are defined; a general approach to the design of optimization software programs is outlined; and drawings and diagrams are shown for examples involving (1) the conceptual design of an aircraft, (2) the aerodynamic optimization of an airfoil, (3) the design of an automotive-engine connecting rod, and (4) the optimization of a 'ski-jump' to assist aircraft in taking off from a very short ship deck.

  15. Optimization theory with applications

    CERN Document Server

    Pierre, Donald A

    1987-01-01

    Optimization principles are of undisputed importance in modern design and system operation. They can be used for many purposes: optimal design of systems, optimal operation of systems, determination of performance limitations of systems, or simply the solution of sets of equations. While most books on optimization are limited to essentially one approach, this volume offers a broad spectrum of approaches, with emphasis on basic techniques from both classical and modern work.After an introductory chapter introducing those system concepts that prevail throughout optimization problems of all typ

  16. Concepts of combinatorial optimization

    CERN Document Server

    Paschos, Vangelis Th

    2014-01-01

    Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management.  The three volumes of the Combinatorial Optimization series aim to cover a wide range  of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization.Concepts of Combinatorial Optimization, is divided into three parts:- On the complexity of combinatorial optimization problems, presenting basics about worst-case and randomi

  17. Introduction to Continuous Optimization

    DEFF Research Database (Denmark)

    Andreasson, Niclas; Evgrafov, Anton; Patriksson, Michael

    optimal solutions for continuous optimization models. The main part of the mathematical material therefore concerns the analysis and linear algebra that underlie the workings of convexity and duality, and necessary/sufficient local/global optimality conditions for continuous optimization problems. Natural...... algorithms are then developed from these optimality conditions, and their most important convergence characteristics are analyzed. The book answers many more questions of the form “Why?” and “Why not?” than “How?”. We use only elementary mathematics in the development of the book, yet are rigorous throughout...

  18. Evolutionary constrained optimization

    CERN Document Server

    Deb, Kalyanmoy

    2015-01-01

    This book makes available a self-contained collection of modern research addressing the general constrained optimization problems using evolutionary algorithms. Broadly the topics covered include constraint handling for single and multi-objective optimizations; penalty function based methodology; multi-objective based methodology; new constraint handling mechanism; hybrid methodology; scaling issues in constrained optimization; design of scalable test problems; parameter adaptation in constrained optimization; handling of integer, discrete and mix variables in addition to continuous variables; application of constraint handling techniques to real-world problems; and constrained optimization in dynamic environment. There is also a separate chapter on hybrid optimization, which is gaining lots of popularity nowadays due to its capability of bridging the gap between evolutionary and classical optimization. The material in the book is useful to researchers, novice, and experts alike. The book will also be useful...

  19. Interactive Topology Optimization

    DEFF Research Database (Denmark)

    Nobel-Jørgensen, Morten

    Interactivity is the continuous interaction between the user and the application to solve a task. Topology optimization is the optimization of structures in order to improve stiffness or other objectives. The goal of the thesis is to explore how topology optimization can be used in applications...... on theory of from human-computer interaction which is described in Chapter 2. Followed by a description of the foundations of topology optimization in Chapter 3. Our applications for topology optimization in 2D and 3D are described in Chapter 4 and a game which trains the human intuition of topology...... optimization is presented in Chapter 5. Topology optimization can also be used as an interactive modeling tool with local control which is presented in Chapter 6. Finally, Chapter 7 contains a summary of the findings and concludes the dissertation. Most of the presented applications of the thesis are available...

  20. Particle Swarm Optimization

    Science.gov (United States)

    Venter, Gerhard; Sobieszczanski-Sobieski Jaroslaw

    2002-01-01

    The purpose of this paper is to show how the search algorithm known as particle swarm optimization performs. Here, particle swarm optimization is applied to structural design problems, but the method has a much wider range of possible applications. The paper's new contributions are improvements to the particle swarm optimization algorithm and conclusions and recommendations as to the utility of the algorithm, Results of numerical experiments for both continuous and discrete applications are presented in the paper. The results indicate that the particle swarm optimization algorithm does locate the constrained minimum design in continuous applications with very good precision, albeit at a much higher computational cost than that of a typical gradient based optimizer. However, the true potential of particle swarm optimization is primarily in applications with discrete and/or discontinuous functions and variables. Additionally, particle swarm optimization has the potential of efficient computation with very large numbers of concurrently operating processors.

  1. Workshop on Computational Optimization

    CERN Document Server

    2015-01-01

    Our everyday life is unthinkable without optimization. We try to minimize our effort and to maximize the achieved profit. Many real world and industrial problems arising in engineering, economics, medicine and other domains can be formulated as optimization tasks. This volume is a comprehensive collection of extended contributions from the Workshop on Computational Optimization 2013. It presents recent advances in computational optimization. The volume includes important real life problems like parameter settings for controlling processes in bioreactor, resource constrained project scheduling, problems arising in transport services, error correcting codes, optimal system performance and energy consumption and so on. It shows how to develop algorithms for them based on new metaheuristic methods like evolutionary computation, ant colony optimization, constrain programming and others.

  2. Optimal placement of capacito

    Directory of Open Access Journals (Sweden)

    N. Gnanasekaran

    2016-06-01

    Full Text Available Optimal size and location of shunt capacitors in the distribution system plays a significant role in minimizing the energy loss and the cost of reactive power compensation. This paper presents a new efficient technique to find optimal size and location of shunt capacitors with the objective of minimizing cost due to energy loss and reactive power compensation of distribution system. A new Shark Smell Optimization (SSO algorithm is proposed to solve the optimal capacitor placement problem satisfying the operating constraints. The SSO algorithm is a recently developed metaheuristic optimization algorithm conceptualized using the shark’s hunting ability. It uses a momentum incorporated gradient search and a rotational movement based local search for optimization. To demonstrate the applicability of proposed method, it is tested on IEEE 34-bus and 118-bus radial distribution systems. The simulation results obtained are compared with previous methods reported in the literature and found to be encouraging.

  3. Optimization of Inventory

    OpenAIRE

    PROKOPOVÁ, Nikola

    2017-01-01

    The subject of this thesis is optimization of inventory in selected organization. Inventory optimization is a very important topic in each organization because it reduces storage costs. At the beginning the inventory theory is presented. It shows the meaning and types of inventory, inventory control and also different methods and models of inventory control. Inventory optimization in the enterprise can be reached by using models of inventory control. In the second part the company on which is...

  4. Search engine optimization

    OpenAIRE

    Marolt, Klemen

    2013-01-01

    Search engine optimization techniques, often shortened to “SEO,” should lead to first positions in organic search results. Some optimization techniques do not change over time, yet still form the basis for SEO. However, as the Internet and web design evolves dynamically, new optimization techniques flourish and flop. Thus, we looked at the most important factors that can help to improve positioning in search results. It is important to emphasize that none of the techniques can guarantee high ...

  5. LOGISTICS OPTIMIZATION USING ONTOLOGIES

    OpenAIRE

    Hendi , Hayder; Ahmad , Adeel; Bouneffa , Mourad; Fonlupt , Cyril

    2014-01-01

    International audience; Logistics processes involve complex physical flows and integration of different elements. It is widely observed that the uncontrolled processes can decline the state of logistics. The optimization of logistic processes can support the desired growth and consistent continuity of logistics. In this paper, we present a software framework for logistic processes optimization. It primarily defines logistic ontologies and then optimize them. It intends to assist the design of...

  6. Optimization and approximation

    CERN Document Server

    Pedregal, Pablo

    2017-01-01

    This book provides a basic, initial resource, introducing science and engineering students to the field of optimization. It covers three main areas: mathematical programming, calculus of variations and optimal control, highlighting the ideas and concepts and offering insights into the importance of optimality conditions in each area. It also systematically presents affordable approximation methods. Exercises at various levels have been included to support the learning process.

  7. Dictionary descent in optimization

    OpenAIRE

    Temlyakov, Vladimir

    2015-01-01

    The problem of convex optimization is studied. Usually in convex optimization the minimization is over a d-dimensional domain. Very often the convergence rate of an optimization algorithm depends on the dimension d. The algorithms studied in this paper utilize dictionaries instead of a canonical basis used in the coordinate descent algorithms. We show how this approach allows us to reduce dimensionality of the problem. Also, we investigate which properties of a dictionary are beneficial for t...

  8. POSTDOC : THE HUMAN OPTIMIZATION

    OpenAIRE

    Satish Gajawada

    2013-01-01

    This paper is dedicated to everyone who is interested in the Artificial Intelligence. John Henry Holland proposed Genetic Algorithm in the early 1970s. Ant Colony Optimization was proposed by Marco Dorigo in 1992. Particle Swarm Optimization was introduced by Kennedy and Eberhart in 1995. Storn and Price introduced Differential Evolution in 1996. K.M. Passino introduced Bacterial Foraging Optimization Algorithm in 2002. In 2003, X.L. Li proposed Artificial Fish Swarm Algorithm....

  9. Optimization with Extremal Dynamics

    International Nuclear Information System (INIS)

    Boettcher, Stefan; Percus, Allon G.

    2001-01-01

    We explore a new general-purpose heuristic for finding high-quality solutions to hard discrete optimization problems. The method, called extremal optimization, is inspired by self-organized criticality, a concept introduced to describe emergent complexity in physical systems. Extremal optimization successively updates extremely undesirable variables of a single suboptimal solution, assigning them new, random values. Large fluctuations ensue, efficiently exploring many local optima. We use extremal optimization to elucidate the phase transition in the 3-coloring problem, and we provide independent confirmation of previously reported extrapolations for the ground-state energy of ±J spin glasses in d=3 and 4

  10. Maintenance optimization after RCM

    International Nuclear Information System (INIS)

    Doyle, E.K.; Lee, C.-G.; Cho, D.

    2005-01-01

    Variant forms of RCM (Reliability Centered Maintenance) have been the maintenance optimizing tools of choice in industry for the last 20 years. Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy whereby decisions are based on statistical analysis of historical failure data are now being evaluated. The evaluation includes a requirement to demonstrate that earlier optimization projects have long term positive impacts. This proved to be a significant challenge. Eventually a methodology was developed using Crowe/AMSAA (Army Materials Systems Analysis Activity) plots to justify expenditures on further optimization efforts. (authors)

  11. Sequential stochastic optimization

    CERN Document Server

    Cairoli, Renzo

    1996-01-01

    Sequential Stochastic Optimization provides mathematicians and applied researchers with a well-developed framework in which stochastic optimization problems can be formulated and solved. Offering much material that is either new or has never before appeared in book form, it lucidly presents a unified theory of optimal stopping and optimal sequential control of stochastic processes. This book has been carefully organized so that little prior knowledge of the subject is assumed; its only prerequisites are a standard graduate course in probability theory and some familiarity with discrete-paramet

  12. Optimization under Uncertainty

    KAUST Repository

    Lopez, Rafael H.

    2016-01-06

    The goal of this poster is to present the main approaches to optimization of engineering systems in the presence of uncertainties. We begin by giving an insight about robust optimization. Next, we detail how to deal with probabilistic constraints in optimization, the so called the reliability based design. Subsequently, we present the risk optimization approach, which includes the expected costs of failure in the objective function. After that the basic description of each approach is given, the projects developed by CORE are presented. Finally, the main current topic of research of CORE is described.

  13. Beam optimization: improving methodology

    International Nuclear Information System (INIS)

    Quinteiro, Guillermo F.

    2004-01-01

    Different optimization techniques commonly used in biology and food technology allow a systematic and complete analysis of response functions. In spite of the great interest in medical and nuclear physics in the problem of optimizing mixed beams, little attention has been given to sophisticate mathematical tools. Indeed, many techniques are perfectly suited to the typical problem of beam optimization. This article is intended as a guide to the use of two methods, namely Response Surface Methodology and Simplex, that are expected to fasten the optimization process and, meanwhile give more insight into the relationships among the dependent variables controlling the response

  14. Integer and combinatorial optimization

    CERN Document Server

    Nemhauser, George L

    1999-01-01

    Rave reviews for INTEGER AND COMBINATORIAL OPTIMIZATION ""This book provides an excellent introduction and survey of traditional fields of combinatorial optimization . . . It is indeed one of the best and most complete texts on combinatorial optimization . . . available. [And] with more than 700 entries, [it] has quite an exhaustive reference list.""-Optima ""A unifying approach to optimization problems is to formulate them like linear programming problems, while restricting some or all of the variables to the integers. This book is an encyclopedic resource for such f

  15. Optimization : insights and applications

    CERN Document Server

    Brinkhuis, Jan

    2005-01-01

    This self-contained textbook is an informal introduction to optimization through the use of numerous illustrations and applications. The focus is on analytically solving optimization problems with a finite number of continuous variables. In addition, the authors provide introductions to classical and modern numerical methods of optimization and to dynamic optimization. The book's overarching point is that most problems may be solved by the direct application of the theorems of Fermat, Lagrange, and Weierstrass. The authors show how the intuition for each of the theoretical results can be s

  16. Initiating statistical maintenance optimization

    International Nuclear Information System (INIS)

    Doyle, E. Kevin; Tuomi, Vesa; Rowley, Ian

    2007-01-01

    Since the 1980 s maintenance optimization has been centered around various formulations of Reliability Centered Maintenance (RCM). Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy includes evaluation of statistical optimization techniques. A review of successful pilot efforts in this direction is provided as well as initial work with graphical analysis. The present situation reguarding data sourcing, the principle impediment to use of stochastic methods in previous years, is discussed. The use of Crowe/AMSAA (Army Materials Systems Analysis Activity) plots is demonstrated from the point of view of justifying expenditures in optimization efforts. (author)

  17. Stochastic optimization methods

    CERN Document Server

    Marti, Kurt

    2008-01-01

    Optimization problems arising in practice involve random model parameters. This book features many illustrations, several examples, and applications to concrete problems from engineering and operations research.

  18. Optimization and Optimal Control in Automotive Systems

    NARCIS (Netherlands)

    Waschl, H.; Kolmanovsky, I.V.; Steinbuch, M.; Re, del L.

    2014-01-01

    This book demonstrates the use of the optimization techniques that are becoming essential to meet the increasing stringency and variety of requirements for automotive systems. It shows the reader how to move away from earlier approaches, based on some degree of heuristics, to the use of more and

  19. A sequential binding mechanism in a PDZ domain

    DEFF Research Database (Denmark)

    Chi, Celestine N; Bach, Anders; Engström, Åke

    2009-01-01

    that ligand binding involves at least a two-step process. By using an ultrarapid continuous-flow mixer, we then detected a hyperbolic dependence of binding rate constants on peptide concentration, corroborating the two-step binding mechanism. Furthermore, we found a similar dependence of the rate constants...

  20. Numerical Optimization in Microfluidics

    DEFF Research Database (Denmark)

    Jensen, Kristian Ejlebjærg

    2017-01-01

    Numerical modelling can illuminate the working mechanism and limitations of microfluidic devices. Such insights are useful in their own right, but one can take advantage of numerical modelling in a systematic way using numerical optimization. In this chapter we will discuss when and how numerical...... optimization is best used....

  1. Optimization of surface maintenance

    International Nuclear Information System (INIS)

    Oeverland, E.

    1990-01-01

    The present conference paper deals with methods of optimizing the surface maintenance of steel-made offshore installations. The paper aims at identifying important approaches to the problems regarding the long-range planning of an economical and cost effective maintenance program. The methods of optimization are based on the obtained experiences from the maintenance of installations on the Norwegian continental shelf. 3 figs

  2. Implementing optimal thinning strategies

    Science.gov (United States)

    Kurt H. Riitters; J. Douglas Brodie

    1984-01-01

    Optimal thinning regimes for achieving several management objectives were derived from two stand-growth simulators by dynamic programming. Residual mean tree volumes were then plotted against stand density management diagrams. The results supported the use of density management diagrams for comparing, checking, and implementing the results of optimization analyses....

  3. Economically optimal thermal insulation

    Energy Technology Data Exchange (ETDEWEB)

    Berber, J.

    1978-10-01

    Exemplary calculations to show that exact adherence to the demands of the thermal insulation ordinance does not lead to an optimal solution with regard to economics. This is independent of the mode of financing. Optimal thermal insulation exceeds the values given in the thermal insulation ordinance.

  4. Optimizing Plutonium stock management

    International Nuclear Information System (INIS)

    Niquil, Y.; Guillot, J.

    1997-01-01

    Plutonium from spent fuel reprocessing is reused in new MOX assemblies. Since plutonium isotopic composition deteriorates with time, it is necessary to optimize plutonium stock management over a long period, to guarantee safe procurement, and contribute to a nuclear fuel cycle policy at the lowest cost. This optimization is provided by the prototype software POMAR

  5. Optimal Aging and Death

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Strulik, Holger

    2010-01-01

    This study introduces physiological aging into a simple model of optimal intertemporal consumption. In this endeavor we draw on the natural science literature on aging. According to the purposed theory, the speed of the aging process and the time of death are endogenously determined by optimal...

  6. Asymptotically Optimal Agents

    OpenAIRE

    Lattimore, Tor; Hutter, Marcus

    2011-01-01

    Artificial general intelligence aims to create agents capable of learning to solve arbitrary interesting problems. We define two versions of asymptotic optimality and prove that no agent can satisfy the strong version while in some cases, depending on discounting, there does exist a non-computable weak asymptotically optimal agent.

  7. Natural selection and optimality

    International Nuclear Information System (INIS)

    Torres, J.L.

    1989-01-01

    It is assumed that Darwin's principle translates into optimal regimes of operation along metabolical pathways in an ecological system. Fitness is then defined in terms of the distance of a given individual's thermodynamic parameters from their optimal values. The method is illustrated testing maximum power as a criterion of merit satisfied in ATP synthesis. (author). 26 refs, 2 figs

  8. Optimization in power systems

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Geraldo R.M. da [Sao Paulo Univ., Sao Carlos, SP (Brazil). Escola de Engenharia

    1994-12-31

    This paper discusses, partially, the advantages and the disadvantages of the optimal power flow. It shows some of the difficulties of implementation and proposes solutions. An analysis is made comparing the power flow, BIGPOWER/CESP, and the optimal power flow, FPO/SEL, developed by the author, when applied to the CEPEL-ELETRONORTE and CESP systems. (author) 8 refs., 5 tabs.

  9. Symbiotic Optimization of Behavior

    Science.gov (United States)

    2015-05-01

    SYMBIOTIC OPTIMIZATION OF BEHAVIOR UNIVERSITY OF WASHINGTON MAY 2015 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED...2014 4. TITLE AND SUBTITLE SYMBIOTIC OPTIMIZATION OF BEHAVIOR 5a. CONTRACT NUMBER FA8750-12-1-0304 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT

  10. Perceptually optimal color reproduction

    NARCIS (Netherlands)

    Yendrikhovskij, S.N.; Blommaert, F.J.J.; Ridder, de H.; Rogowitz, B.E.; Pappas, T.N.

    1998-01-01

    What requirements do people place on optimal color reproduction of real-life scenes? We suggest that when people look at images containing familiar categories of objects, two primary factors shape their subjective impression of how optimal colors are reproduced: perceived naturalness and perceived

  11. Bolt Thread Stress Optimization

    DEFF Research Database (Denmark)

    Pedersen, Niels Leergaard

    2012-01-01

    of threads and therefore indirectly the bolt fatigue life. The root shape is circular, and from shape optimization for minimum stress concentration it is well known that the circular shape is seldom optimal. An axisymmetric Finite Element (FE) formulation is used to analyze the bolted connection, and a study...... is performed to establish the need for contact modeling with regard to finding the correct stress concentration factor. Optimization is performed with a simple parameterization with two design variables. Stress reduction of up to 9% is found in the optimization process, and some similarities are found...... in the optimized designs leading to the proposal of a new standard. The reductions in the stress are achieved by rather simple changes made to the cutting tool....

  12. Overall bolt stress optimization

    DEFF Research Database (Denmark)

    Pedersen, Niels Leergaard

    2013-01-01

    The state of stress in bolts and nuts with International Organization for Standardization metric thread design is examined and optimized. The assumed failure mode is fatigue, so the applied preload and the load amplitude together with the stress concentrations define the connection strength....... Maximum stress in the bolt is found at the fillet under the head, at the thread start, or at the thread root. To minimize the stress concentration, shape optimization is applied. Nut shape optimization also has a positive effect on the maximum stress. The optimization results show that designing a nut......, which results in a more evenly distribution of load along the engaged thread, has a limited influence on the maximum stress due to the stress concentration at the first thread root. To further reduce the maximum stress, the transition from bolt shank to the thread must be optimized. Stress reduction...

  13. Workshop on Computational Optimization

    CERN Document Server

    2016-01-01

    This volume is a comprehensive collection of extended contributions from the Workshop on Computational Optimization 2014, held at Warsaw, Poland, September 7-10, 2014. The book presents recent advances in computational optimization. The volume includes important real problems like parameter settings for controlling processes in bioreactor and other processes, resource constrained project scheduling, infection distribution, molecule distance geometry, quantum computing, real-time management and optimal control, bin packing, medical image processing, localization the abrupt atmospheric contamination source and so on. It shows how to develop algorithms for them based on new metaheuristic methods like evolutionary computation, ant colony optimization, constrain programming and others. This research demonstrates how some real-world problems arising in engineering, economics, medicine and other domains can be formulated as optimization tasks.

  14. Flight plan optimization

    Science.gov (United States)

    Dharmaseelan, Anoop; Adistambha, Keyne D.

    2015-05-01

    Fuel cost accounts for 40 percent of the operating cost of an airline. Fuel cost can be minimized by planning a flight on optimized routes. The routes can be optimized by searching best connections based on the cost function defined by the airline. The most common algorithm that used to optimize route search is Dijkstra's. Dijkstra's algorithm produces a static result and the time taken for the search is relatively long. This paper experiments a new algorithm to optimize route search which combines the principle of simulated annealing and genetic algorithm. The experimental results of route search, presented are shown to be computationally fast and accurate compared with timings from generic algorithm. The new algorithm is optimal for random routing feature that is highly sought by many regional operators.

  15. System performance optimization

    International Nuclear Information System (INIS)

    Bednarz, R.J.

    1978-01-01

    The System Performance Optimization has become an important and difficult field for large scientific computer centres. Important because the centres must satisfy increasing user demands at the lowest possible cost. Difficult because the System Performance Optimization requires a deep understanding of hardware, software and workload. The optimization is a dynamic process depending on the changes in hardware configuration, current level of the operating system and user generated workload. With the increasing complication of the computer system and software, the field for the optimization manoeuvres broadens. The hardware of two manufacturers IBM and CDC is discussed. Four IBM and two CDC operating systems are described. The description concentrates on the organization of the operating systems, the job scheduling and I/O handling. The performance definitions, workload specification and tools for the system stimulation are given. The measurement tools for the System Performance Optimization are described. The results of the measurement and various methods used for the operating system tuning are discussed. (Auth.)

  16. Optimized manufacturable porous materials

    DEFF Research Database (Denmark)

    Andreassen, Erik; Andreasen, Casper Schousboe; Jensen, Jakob Søndergaard

    Topology optimization has been used to design two-dimensional material structures with specific elastic properties, but optimized designs of three-dimensional material structures are more scarsely seen. Partly because it requires more computational power, and partly because it is a major challenge...... to include manufacturing constraints in the optimization. This work focuses on incorporating the manufacturability into the optimization procedure, allowing the resulting material structure to be manufactured directly using rapid manufacturing techniques, such as selective laser melting/sintering (SLM....../S). The available manufacturing methods are best suited for porous materials (one constituent and void), but the optimization procedure can easily include more constituents. The elasticity tensor is found from one unit cell using the homogenization method together with a standard finite element (FE) discretization...

  17. Modern optimization with R

    CERN Document Server

    Cortez, Paulo

    2014-01-01

    The goal of this book is to gather in a single document the most relevant concepts related to modern optimization methods, showing how such concepts and methods can be addressed using the open source, multi-platform R tool. Modern optimization methods, also known as metaheuristics, are particularly useful for solving complex problems for which no specialized optimization algorithm has been developed. These methods often yield high quality solutions with a more reasonable use of computational resources (e.g. memory and processing effort). Examples of popular modern methods discussed in this book are: simulated annealing; tabu search; genetic algorithms; differential evolution; and particle swarm optimization. This book is suitable for undergraduate and graduate students in Computer Science, Information Technology, and related areas, as well as data analysts interested in exploring modern optimization methods using R.

  18. 4th Optimization Day

    CERN Document Server

    Eberhard, Andrew; Ralph, Daniel; Glover, Barney M

    1999-01-01

    Although the monograph Progress in Optimization I: Contributions from Aus­ tralasia grew from the idea of publishing a proceedings of the Fourth Optimiza­ tion Day, held in July 1997 at the Royal Melbourne Institute of Technology, the focus soon changed to a refereed volume in optimization. The intention is to publish a similar book annually, following each Optimization Day. The idea of having an annual Optimization Day was conceived by Barney Glover; the first of these Optimization Days was held in 1994 at the University of Ballarat. Barney hoped that such a yearly event would bring together the many, but widely dispersed, researchers in Australia who were publishing in optimization and related areas such as control. The first Optimization Day event was followed by similar conferences at The University of New South Wales (1995), The University of Melbourne (1996), the Royal Melbourne Institute of Technology (1997), and The University of Western Australia (1998). The 1999 conference will return to Ballarat ...

  19. Encyclopedia of optimization

    CERN Document Server

    Pardalos, Panos

    2001-01-01

    Optimization problems are widespread in the mathematical modeling of real world systems and their applications arise in all branches of science, applied science and engineering. The goal of the Encyclopedia of Optimization is to introduce the reader to a complete set of topics in order to show the spectrum of recent research activities and the richness of ideas in the development of theories, algorithms and the applications of optimization. It is directed to a diverse audience of students, scientists, engineers, decision makers and problem solvers in academia, business, industry, and government.

  20. Optimization of Antivirus Software

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The paper describes the main techniques used in development of computer antivirus software applications. For this particular category of software, are identified and defined optimum criteria that helps determine which solution is better and what are the objectives of the optimization process. From the general viewpoint of software optimization are presented methods and techniques that are applied at code development level. Regarding the particularities of antivirus software, the paper analyzes some of the optimization concepts applied to this category of applications

  1. Nonlinear optimal control theory

    CERN Document Server

    Berkovitz, Leonard David

    2012-01-01

    Nonlinear Optimal Control Theory presents a deep, wide-ranging introduction to the mathematical theory of the optimal control of processes governed by ordinary differential equations and certain types of differential equations with memory. Many examples illustrate the mathematical issues that need to be addressed when using optimal control techniques in diverse areas. Drawing on classroom-tested material from Purdue University and North Carolina State University, the book gives a unified account of bounded state problems governed by ordinary, integrodifferential, and delay systems. It also dis

  2. What is unrealistic optimism?

    Science.gov (United States)

    Jefferson, Anneli; Bortolotti, Lisa; Kuzmanovic, Bojana

    2017-04-01

    Here we consider the nature of unrealistic optimism and other related positive illusions. We are interested in whether cognitive states that are unrealistically optimistic are belief states, whether they are false, and whether they are epistemically irrational. We also ask to what extent unrealistically optimistic cognitive states are fixed. Based on the classic and recent empirical literature on unrealistic optimism, we offer some preliminary answers to these questions, thereby laying the foundations for answering further questions about unrealistic optimism, such as whether it has biological, psychological, or epistemic benefits. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  4. Optimization of refrigeration machinery

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Goeran [University Coll. of Eskilstuna/Vaesteraas (SE)

    1991-11-01

    This paper reports the application of thermoeconomics to the optimization of a heat pump. The method is suited for application to thermodynamic processes and yields exergy losses. The marginal cost of an arbitary variable can also be calculated. The efficiencies of the compressor, condenser, evaporator and electric motor are chosen as variables to be optimized. Parameters such as the price of electricity and the temperature of the delivered heat may vary between optimizations, and results are presented for different parameter values. The results show that the efficiency of the electric motor is the most important variable. (author).

  5. Evolution strategies for robust optimization

    NARCIS (Netherlands)

    Kruisselbrink, Johannes Willem

    2012-01-01

    Real-world (black-box) optimization problems often involve various types of uncertainties and noise emerging in different parts of the optimization problem. When this is not accounted for, optimization may fail or may yield solutions that are optimal in the classical strict notion of optimality, but

  6. Optimization of photonic crystal cavities

    DEFF Research Database (Denmark)

    Wang, Fengwen; Sigmund, Ole

    2017-01-01

    We present optimization of photonic crystal cavities. The optimization problem is formulated to maximize the Purcell factor of a photonic crystal cavity. Both topology optimization and air-hole-based shape optimization are utilized for the design process. Numerical results demonstrate...... that the Purcell factor of the photonic crystal cavity can be significantly improved through optimization....

  7. Optimal Aerocapture Guidance

    Data.gov (United States)

    National Aeronautics and Space Administration — The main goal of my research is to develop, implement, verify, and validate an optimal numerical predictor-corrector aerocapture guidance algorithm that is...

  8. Optimal primitive reference frames

    International Nuclear Information System (INIS)

    Jennings, David

    2011-01-01

    We consider the smallest possible directional reference frames allowed and determine the best one can ever do in preserving quantum information in various scenarios. We find that for the preservation of a single spin state, two orthogonal spins are optimal primitive reference frames; and in a product state, they do approximately 22% as well as an infinite-sized classical frame. By adding a small amount of entanglement to the reference frame, this can be raised to 2(2/3) 5 =26%. Under the different criterion of entanglement preservation, a very similar optimal reference frame is found; however, this time it is for spins aligned at an optimal angle of 87 deg. In this case 24% of the negativity is preserved. The classical limit is considered numerically, and indicates under the criterion of entanglement preservation, that 90 deg. is selected out nonmonotonically, with a peak optimal angle of 96.5 deg. for L=3 spins.

  9. Linearly constrained minimax optimization

    DEFF Research Database (Denmark)

    Madsen, Kaj; Schjær-Jacobsen, Hans

    1978-01-01

    We present an algorithm for nonlinear minimax optimization subject to linear equality and inequality constraints which requires first order partial derivatives. The algorithm is based on successive linear approximations to the functions defining the problem. The resulting linear subproblems...

  10. Optimization in liner shipping

    DEFF Research Database (Denmark)

    Brouer, Berit Dangaard; Karsten, Christian Vad; Pisinger, David

    2017-01-01

    Seaborne trade is the lynchpin in almost every international supply chain, and about 90% of non-bulk cargo worldwide is transported by container. In this survey we give an overview of data-driven optimization problems in liner shipping. Research in liner shipping is motivated by a need for handling...... still more complex decision problems, based on big data sets and going across several organizational entities. Moreover, liner shipping optimization problems are pushing the limits of optimization methods, creating a new breeding ground for advanced modelling and solution methods. Starting from liner...... shipping network design, we consider the problem of container routing and speed optimization. Next, we consider empty container repositioning and stowage planning as well as disruption management. In addition, the problem of bunker purchasing is considered in depth. In each section we give a clear problem...

  11. Stochastic and global optimization

    National Research Council Canada - National Science Library

    Dzemyda, Gintautas; Šaltenis, Vydūnas; Zhilinskas, A; Mockus, Jonas

    2002-01-01

    ... and Effectiveness of Controlled Random Search E. M. T. Hendrix, P. M. Ortigosa and I. García 129 9. Discrete Backtracking Adaptive Search for Global Optimization B. P. Kristinsdottir, Z. B. Zabinsky and...

  12. Topology optimized microbioreactors

    DEFF Research Database (Denmark)

    Schäpper, Daniel; Lencastre Fernandes, Rita; Eliasson Lantz, Anna

    2011-01-01

    This article presents the fusion of two hitherto unrelated fields—microbioreactors and topology optimization. The basis for this study is a rectangular microbioreactor with homogeneously distributed immobilized brewers yeast cells (Saccharomyces cerevisiae) that produce a recombinant protein...

  13. Dynamic stochastic optimization

    CERN Document Server

    Ermoliev, Yuri; Pflug, Georg

    2004-01-01

    Uncertainties and changes are pervasive characteristics of modern systems involving interactions between humans, economics, nature and technology. These systems are often too complex to allow for precise evaluations and, as a result, the lack of proper management (control) may create significant risks. In order to develop robust strategies we need approaches which explic­ itly deal with uncertainties, risks and changing conditions. One rather general approach is to characterize (explicitly or implicitly) uncertainties by objec­ tive or subjective probabilities (measures of confidence or belief). This leads us to stochastic optimization problems which can rarely be solved by using the standard deterministic optimization and optimal control methods. In the stochastic optimization the accent is on problems with a large number of deci­ sion and random variables, and consequently the focus ofattention is directed to efficient solution procedures rather than to (analytical) closed-form solu­ tions. Objective an...

  14. Stochastic optimization methods

    CERN Document Server

    Marti, Kurt

    2005-01-01

    Optimization problems arising in practice involve random parameters. For the computation of robust optimal solutions, i.e., optimal solutions being insensitive with respect to random parameter variations, deterministic substitute problems are needed. Based on the distribution of the random data, and using decision theoretical concepts, optimization problems under stochastic uncertainty are converted into deterministic substitute problems. Due to the occurring probabilities and expectations, approximative solution techniques must be applied. Deterministic and stochastic approximation methods and their analytical properties are provided: Taylor expansion, regression and response surface methods, probability inequalities, First Order Reliability Methods, convex approximation/deterministic descent directions/efficient points, stochastic approximation methods, differentiation of probability and mean value functions. Convergence results of the resulting iterative solution procedures are given.

  15. Cooperative Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2009-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a novel optimization algorithm based on the social foraging behavior of E. coli bacteria. This paper presents a variation on the original BFO algorithm, namely, the Cooperative Bacterial Foraging Optimization (CBFO, which significantly improve the original BFO in solving complex optimization problems. This significant improvement is achieved by applying two cooperative approaches to the original BFO, namely, the serial heterogeneous cooperation on the implicit space decomposition level and the serial heterogeneous cooperation on the hybrid space decomposition level. The experiments compare the performance of two CBFO variants with the original BFO, the standard PSO and a real-coded GA on four widely used benchmark functions. The new method shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  16. Optimal mixture experiments

    CERN Document Server

    Sinha, B K; Pal, Manisha; Das, P

    2014-01-01

    The book dwells mainly on the optimality aspects of mixture designs. As mixture models are a special case of regression models, a general discussion on regression designs has been presented, which includes topics like continuous designs, de la Garza phenomenon, Loewner order domination, Equivalence theorems for different optimality criteria and standard optimality results for single variable polynomial regression and multivariate linear and quadratic regression models. This is followed by a review of the available literature on estimation of parameters in mixture models. Based on recent research findings, the volume also introduces optimal mixture designs for estimation of optimum mixing proportions in different mixture models, which include Scheffé’s quadratic model, Darroch-Waller model, log- contrast model, mixture-amount models, random coefficient models and multi-response model.  Robust mixture designs and mixture designs in blocks have been also reviewed. Moreover, some applications of mixture desig...

  17. RF Gun Optimization Study

    International Nuclear Information System (INIS)

    Alicia Hofler; Pavel Evtushenko

    2007-01-01

    Injector gun design is an iterative process where the designer optimizes a few nonlinearly interdependent beam parameters to achieve the required beam quality for a particle accelerator. Few tools exist to automate the optimization process and thoroughly explore the parameter space. The challenging beam requirements of new accelerator applications such as light sources and electron cooling devices drive the development of RF and SRF photo injectors. A genetic algorithm (GA) has been successfully used to optimize DC photo injector designs at Cornell University [1] and Jefferson Lab [2]. We propose to apply GA techniques to the design of RF and SRF gun injectors. In this paper, we report on the initial phase of the study where we model and optimize a system that has been benchmarked with beam measurements and simulation

  18. Handbook of simulation optimization

    CERN Document Server

    Fu, Michael C

    2014-01-01

    The Handbook of Simulation Optimization presents an overview of the state of the art of simulation optimization, providing a survey of the most well-established approaches for optimizing stochastic simulation models and a sampling of recent research advances in theory and methodology. Leading contributors cover such topics as discrete optimization via simulation, ranking and selection, efficient simulation budget allocation, random search methods, response surface methodology, stochastic gradient estimation, stochastic approximation, sample average approximation, stochastic constraints, variance reduction techniques, model-based stochastic search methods and Markov decision processes. This single volume should serve as a reference for those already in the field and as a means for those new to the field for understanding and applying the main approaches. The intended audience includes researchers, practitioners and graduate students in the business/engineering fields of operations research, management science,...

  19. Optimally Locating MARFORRES Units

    OpenAIRE

    Salmeron, Javier; Dell, Rob

    2015-01-01

    Javier Salmeron and Rob Dell The U.S. Marine Forces Reserve (USMCR, MARFORRES) is conducting realignment studies where discretionary changes may benefit from formal mathematical analysis. This study has developed an optimization tool to guide and/or support Commander, MARFORRES (CMFR) decisions. A prototype of the optimization tool has been tested with data from the units and Reserve Training Centers (RTCs) in the San Francisco, CA and Sacramento, CA areas. Prepared for: MARFORRES, POC:...

  20. Optimization of Bolt Stress

    DEFF Research Database (Denmark)

    Pedersen, Niels Leergaard

    2013-01-01

    The state of stress in bolts and nuts with ISO metric thread design is examined and optimized. The assumed failure mode is fatigue so the applied preload and the load amplitude together with the stress concentrations define the connection strength. Maximum stress in the bolt is found at, the fillet...... under the head, at the thread start or at the thread root. To minimize the stress concentration shape optimization is applied....

  1. Optimization of Antivirus Software

    OpenAIRE

    Catalin BOJA; Adrian VISOIU

    2007-01-01

    The paper describes the main techniques used in development of computer antivirus software applications. For this particular category of software, are identified and defined optimum criteria that helps determine which solution is better and what are the objectives of the optimization process. From the general viewpoint of software optimization are presented methods and techniques that are applied at code development level. Regarding the particularities of antivirus software, the paper analyze...

  2. Bargaining with Optimism

    OpenAIRE

    Yildiz, Muhamet

    2011-01-01

    Excessive optimism is a prominent explanation for bargaining delays. Recent results demonstrate that optimism plays a subtle role in bargaining, and its careful analysis may shed valuable insights into negotiation behavior. This article reviews some of these results, focusing on the following findings. First, when there is a nearby deadline, optimistic players delay the agreement to the last period before the deadline, replicating a broad empirical regularity known as the deadline effect. Sec...

  3. Tax optimization of companies

    OpenAIRE

    Dědinová, Pavla

    2017-01-01

    This diploma thesis deals with tax optimization of companies. The thesis is divided into two main parts - the theoretical and practical part. The introduction of the theoretical part describes the history of taxes, their basic characteristics and the importance of their collection for today's society. Subsequently, the tax system of the Czech Republic with a focus on value added tax and corporation tax is presented. The practical part deals with specific possibilities of optimization of the a...

  4. Optimal Responsible Investment

    DEFF Research Database (Denmark)

    Jessen, Pernille

    The paper studies retail Socially Responsible Investment and portfolio allocation. It extends conventional portfolio theory by allowing for a personal value based investment decision. When preferences for responsibility enter the framework for mean-variance analysis, it yields an optimal...... responsible investment model. An example of index investing illustrates the theory. Results show that it is crucial for the responsible investor to consider portfolio risk, expected return, and responsibility simultaneously in order to obtain an optimal portfolio. The model enables responsible investors...

  5. Guided randomness in optimization

    CERN Document Server

    Clerc, Maurice

    2015-01-01

    The performance of an algorithm used depends on the GNA. This book focuses on the comparison of optimizers, it defines a stress-outcome approach which can be derived all the classic criteria (median, average, etc.) and other more sophisticated.   Source-codes used for the examples are also presented, this allows a reflection on the ""superfluous chance,"" succinctly explaining why and how the stochastic aspect of optimization could be avoided in some cases.

  6. Regularizing portfolio optimization

    International Nuclear Information System (INIS)

    Still, Susanne; Kondor, Imre

    2010-01-01

    The optimization of large portfolios displays an inherent instability due to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting, which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification 'pressure'. This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade off between the two, depending on the size of the available dataset.

  7. 5th Optimization Day

    CERN Document Server

    Mees, Alistair; Fisher, Mike; Jennings, Les

    2000-01-01

    'Optimization Day' (OD) has been a series of annual mini-conferences in Australia since 1994. The purpose of this series of events is to gather researchers in optimization and its related areas from Australia and their collaborators, in order to exchange new developments of optimization theories, methods and their applications. The first four OD mini-conferences were held in The Uni­ versity of Ballarat (1994), The University of New South Wales (1995), The University of Melbourne (1996) and Royal Melbourne Institute of Technology (1997), respectively. They were all on the eastern coast of Australia. The fifth mini-conference Optimization Days was held at the Centre for Ap­ plied Dynamics and Optimization (CADO), Department of Mathematics and Statistics, The University of Western Australia, Perth, from 29 to 30 June 1998. This is the first time the OD mini-conference has been held at the west­ ern coast of Australia. This fifth OD preceded the International Conference on Optimization: Techniques and Applica...

  8. Learning optimal embedded cascades.

    Science.gov (United States)

    Saberian, Mohammad Javad; Vasconcelos, Nuno

    2012-10-01

    The problem of automatic and optimal design of embedded object detector cascades is considered. Two main challenges are identified: optimization of the cascade configuration and optimization of individual cascade stages, so as to achieve the best tradeoff between classification accuracy and speed, under a detection rate constraint. Two novel boosting algorithms are proposed to address these problems. The first, RCBoost, formulates boosting as a constrained optimization problem which is solved with a barrier penalty method. The constraint is the target detection rate, which is met at all iterations of the boosting process. This enables the design of embedded cascades of known configuration without extensive cross validation or heuristics. The second, ECBoost, searches over cascade configurations to achieve the optimal tradeoff between classification risk and speed. The two algorithms are combined into an overall boosting procedure, RCECBoost, which optimizes both the cascade configuration and its stages under a detection rate constraint, in a fully automated manner. Extensive experiments in face, car, pedestrian, and panda detection show that the resulting detectors achieve an accuracy versus speed tradeoff superior to those of previous methods.

  9. Regularizing portfolio optimization

    Science.gov (United States)

    Still, Susanne; Kondor, Imre

    2010-07-01

    The optimization of large portfolios displays an inherent instability due to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting, which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification 'pressure'. This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade off between the two, depending on the size of the available dataset.

  10. Optimizing countershading camouflage.

    Science.gov (United States)

    Cuthill, Innes C; Sanghera, N Simon; Penacchio, Olivier; Lovell, Paul George; Ruxton, Graeme D; Harris, Julie M

    2016-11-15

    Countershading, the widespread tendency of animals to be darker on the side that receives strongest illumination, has classically been explained as an adaptation for camouflage: obliterating cues to 3D shape and enhancing background matching. However, there have only been two quantitative tests of whether the patterns observed in different species match the optimal shading to obliterate 3D cues, and no tests of whether optimal countershading actually improves concealment or survival. We use a mathematical model of the light field to predict the optimal countershading for concealment that is specific to the light environment and then test this prediction with correspondingly patterned model "caterpillars" exposed to avian predation in the field. We show that the optimal countershading is strongly illumination-dependent. A relatively sharp transition in surface patterning from dark to light is only optimal under direct solar illumination; if there is diffuse illumination from cloudy skies or shade, the pattern provides no advantage over homogeneous background-matching coloration. Conversely, a smoother gradation between dark and light is optimal under cloudy skies or shade. The demonstration of these illumination-dependent effects of different countershading patterns on predation risk strongly supports the comparative evidence showing that the type of countershading varies with light environment.

  11. Totally optimal decision rules

    KAUST Repository

    Amin, Talha

    2017-11-22

    Optimality of decision rules (patterns) can be measured in many ways. One of these is referred to as length. Length signifies the number of terms in a decision rule and is optimally minimized. Another, coverage represents the width of a rule’s applicability and generality. As such, it is desirable to maximize coverage. A totally optimal decision rule is a decision rule that has the minimum possible length and the maximum possible coverage. This paper presents a method for determining the presence of totally optimal decision rules for “complete” decision tables (representations of total functions in which different variables can have domains of differing values). Depending on the cardinalities of the domains, we can either guarantee for each tuple of values of the function that totally optimal rules exist for each row of the table (as in the case of total Boolean functions where the cardinalities are equal to 2) or, for each row, we can find a tuple of values of the function for which totally optimal rules do not exist for this row.

  12. Adaptive Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2011-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a recently developed nature-inspired optimization algorithm, which is based on the foraging behavior of E. coli bacteria. Up to now, BFO has been applied successfully to some engineering problems due to its simplicity and ease of implementation. However, BFO possesses a poor convergence behavior over complex optimization problems as compared to other nature-inspired optimization techniques. This paper first analyzes how the run-length unit parameter of BFO controls the exploration of the whole search space and the exploitation of the promising areas. Then it presents a variation on the original BFO, called the adaptive bacterial foraging optimization (ABFO, employing the adaptive foraging strategies to improve the performance of the original BFO. This improvement is achieved by enabling the bacterial foraging algorithm to adjust the run-length unit parameter dynamically during algorithm execution in order to balance the exploration/exploitation tradeoff. The experiments compare the performance of two versions of ABFO with the original BFO, the standard particle swarm optimization (PSO and a real-coded genetic algorithm (GA on four widely-used benchmark functions. The proposed ABFO shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  13. Totally optimal decision rules

    KAUST Repository

    Amin, Talha M.; Moshkov, Mikhail

    2017-01-01

    Optimality of decision rules (patterns) can be measured in many ways. One of these is referred to as length. Length signifies the number of terms in a decision rule and is optimally minimized. Another, coverage represents the width of a rule’s applicability and generality. As such, it is desirable to maximize coverage. A totally optimal decision rule is a decision rule that has the minimum possible length and the maximum possible coverage. This paper presents a method for determining the presence of totally optimal decision rules for “complete” decision tables (representations of total functions in which different variables can have domains of differing values). Depending on the cardinalities of the domains, we can either guarantee for each tuple of values of the function that totally optimal rules exist for each row of the table (as in the case of total Boolean functions where the cardinalities are equal to 2) or, for each row, we can find a tuple of values of the function for which totally optimal rules do not exist for this row.

  14. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    The volume presents a collaboration between internationally recognized experts on anti-optimization and structural optimization, and summarizes various novel ideas, methodologies and results studied over 20 years...

  15. Handbook of optimization in telecommunications

    CERN Document Server

    Pardalos, Panos M

    2008-01-01

    Covers the field of optimization in telecommunications, and the optimization developments that are frequently applied to telecommunications. This book aims to provide a reference tool for scientists and engineers in telecommunications who depend upon optimization.

  16. Optimization of Metronidazole Emulgel

    Directory of Open Access Journals (Sweden)

    Monica Rao

    2013-01-01

    Full Text Available The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole, a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent, and the dependent variables (responses were a cumulative amount of drug permeated across the dialysis membrane in 24 h ( and spreadability (. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses and . The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 23 factorial design and could provide an effective treatment against topical infections.

  17. Optimization of Heat Exchangers

    International Nuclear Information System (INIS)

    Catton, Ivan

    2010-01-01

    The objective of this research is to develop tools to design and optimize heat exchangers (HE) and compact heat exchangers (CHE) for intermediate loop heat transport systems found in the very high temperature reator (VHTR) and other Generation IV designs by addressing heat transfer surface augmentation and conjugate modeling. To optimize heat exchanger, a fast running model must be created that will allow for multiple designs to be compared quickly. To model a heat exchanger, volume averaging theory, VAT, is used. VAT allows for the conservation of mass, momentum and energy to be solved for point by point in a 3 dimensional computer model of a heat exchanger. The end product of this project is a computer code that can predict an optimal configuration for a heat exchanger given only a few constraints (input fluids, size, cost, etc.). As VAT computer code can be used to model characteristics (pumping power, temperatures, and cost) of heat exchangers more quickly than traditional CFD or experiment, optimization of every geometric parameter simultaneously can be made. Using design of experiment, DOE and genetric algorithms, GE, to optimize the results of the computer code will improve heat exchanger design.

  18. Optimized Kernel Entropy Components.

    Science.gov (United States)

    Izquierdo-Verdiguier, Emma; Laparra, Valero; Jenssen, Robert; Gomez-Chova, Luis; Camps-Valls, Gustau

    2017-06-01

    This brief addresses two main issues of the standard kernel entropy component analysis (KECA) algorithm: the optimization of the kernel decomposition and the optimization of the Gaussian kernel parameter. KECA roughly reduces to a sorting of the importance of kernel eigenvectors by entropy instead of variance, as in the kernel principal components analysis. In this brief, we propose an extension of the KECA method, named optimized KECA (OKECA), that directly extracts the optimal features retaining most of the data entropy by means of compacting the information in very few features (often in just one or two). The proposed method produces features which have higher expressive power. In particular, it is based on the independent component analysis framework, and introduces an extra rotation to the eigen decomposition, which is optimized via gradient-ascent search. This maximum entropy preservation suggests that OKECA features are more efficient than KECA features for density estimation. In addition, a critical issue in both the methods is the selection of the kernel parameter, since it critically affects the resulting performance. Here, we analyze the most common kernel length-scale selection criteria. The results of both the methods are illustrated in different synthetic and real problems. Results show that OKECA returns projections with more expressive power than KECA, the most successful rule for estimating the kernel parameter is based on maximum likelihood, and OKECA is more robust to the selection of the length-scale parameter in kernel density estimation.

  19. Optimization of entanglement witnesses

    Science.gov (United States)

    Lewenstein, M.; Kraus, B.; Cirac, J. I.; Horodecki, P.

    2000-11-01

    An entanglement witness (EW) is an operator that allows the detection of entangled states. We give necessary and sufficient conditions for such operators to be optimal, i.e., to detect entangled states in an optimal way. We show how to optimize general EW, and then we particularize our results to the nondecomposable ones; the latter are those that can detect positive partial transpose entangled states (PPTES's). We also present a method to systematically construct and optimize this last class of operators based on the existence of ``edge'' PPTES's, i.e., states that violate the range separability criterion [Phys. Lett. A 232, 333 (1997)] in an extreme manner. This method also permits a systematic construction of nondecomposable positive maps (PM's). Our results lead to a sufficient condition for entanglement in terms of nondecomposable EW's and PM's. Finally, we illustrate our results by constructing optimal EW acting on H=C2⊗C4. The corresponding PM's constitute examples of PM's with minimal ``qubit'' domains, or-equivalently-minimal Hermitian conjugate codomains.

  20. Optimal Aging and Death

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Strulik, Holger

    2010-01-01

    health investments. At the same time, physiological aspects of the aging process influence optimal savings and health investment. We calibrate the model for the average US male in 2000 and proceed to show that the calibrated model accounts well for the cross-country link between labor productivity......This study introduces physiological aging into a simple model of optimal intertemporal consumption. In this endeavor we draw on the natural science literature on aging. According to the purposed theory, the speed of the aging process and the time of death are endogenously determined by optimal...... and life expectancy in the same year ("the Preston curve"); cross-country income differences can explain differences in life expectancy at age 20 of up to a decade. Moreover, technological change in health care of about 1.1% per year can account for the observed shift in the Preston curve between 1980...

  1. Optimizing UML Class Diagrams

    Directory of Open Access Journals (Sweden)

    Sergievskiy Maxim

    2018-01-01

    Full Text Available Most of object-oriented development technologies rely on the use of the universal modeling language UML; class diagrams play a very important role in the design process play, used to build a software system model. Modern CASE tools, which are the basic tools for object-oriented development, can’t be used to optimize UML diagrams. In this manuscript we will explain how, based on the use of design patterns and anti-patterns, class diagrams could be verified and optimized. Certain transformations can be carried out automatically; in other cases, potential inefficiencies will be indicated and recommendations given. This study also discusses additional CASE tools for validating and optimizing of UML class diagrams. For this purpose, a plugin has been developed that analyzes an XMI file containing a description of class diagrams.

  2. First course in optimization

    CERN Document Server

    Byrne, Charles L

    2014-01-01

    Optimization without Calculus Chapter Summary The Arithmetic Mean-Geometric Mean Inequality An Application of the AGM Inequality: the Number e Extending the AGM Inequality Optimization Using the AGM Inequality The Holder and Minkowski Inequalities Cauchy's Inequality Optimizing using Cauchy's Inequality An Inner Product for Square Matrices Discrete Allocation Problems Geometric Programming Chapter Summary An Example of a GP Problem Posynomials and the GP Problem The Dual GP Problem Solving the GP Problem Solving the DGP Problem Constrained Geometric Programming Basic Analysis Chapter Summary Minima and Infima Limits Completeness Continuity Limsup and Liminf Another View Semi-Continuity Convex Sets Chapter SummaryThe Geometry of Real Euclidean Space A Bit of Topology Convex Sets in RJ More on Projections Linear and Affine Operators on RJ The Fundamental Theorems Block-Matrix Notation Theorems of the Alternative Another Proof of Farkas' Lemma Gordan's Theorem Revisited Vector Spaces and Matrices Chapter Summary...

  3. Manufacturing tolerant topology optimization

    DEFF Research Database (Denmark)

    Sigmund, Ole

    2009-01-01

    In this paper we present an extension of the topology optimization method to include uncertainties during the fabrication of macro, micro and nano structures. More specifically, we consider devices that are manufactured using processes which may result in (uniformly) too thin (eroded) or too thick...... (dilated) structures compared to the intended topology. Examples are MEMS devices manufactured using etching processes, nano-devices manufactured using e-beam lithography or laser micro-machining and macro structures manufactured using milling processes. In the suggested robust topology optimization...... approach, under- and over-etching is modelled by image processing-based "erode" and "dilate" operators and the optimization problem is formulated as a worst case design problem. Applications of the method to the design of macro structures for minimum compliance and micro compliant mechanisms show...

  4. Determining Optimal Decision Version

    Directory of Open Access Journals (Sweden)

    Olga Ioana Amariei

    2014-06-01

    Full Text Available In this paper we start from the calculation of the product cost, applying the method of calculating the cost of hour- machine (THM, on each of the three cutting machines, namely: the cutting machine with plasma, the combined cutting machine (plasma and water jet and the cutting machine with a water jet. Following the calculation of cost and taking into account the precision of manufacturing of each machine, as well as the quality of the processed surface, the optimal decisional version needs to be determined regarding the product manufacturing. To determine the optimal decisional version, we resort firstly to calculating the optimal version on each criterion, and then overall using multiattribute decision methods.

  5. Equipment cost optimization

    International Nuclear Information System (INIS)

    Ribeiro, E.M.; Farias, M.A.; Dreyer, S.R.B.

    1995-01-01

    Considering the importance of the cost of material and equipment in the overall cost profile of an oil company, which in the case of Petrobras, represents approximately 23% of the total operational cost or 10% of the sales, an organization for the optimization of such costs has been established within Petrobras. Programs are developed aiming at: optimization of life-cycle cost of material and equipment; optimization of industrial processes costs through material development. This paper describes the methodology used in the management of the development programs and presents some examples of concluded and ongoing programs, which are conducted in permanent cooperation with suppliers, technical laboratories and research institutions and have been showing relevant results

  6. Optimized packings with applications

    CERN Document Server

    Pintér, János

    2015-01-01

    This volume presents a selection of case studies that address a substantial range of optimized object packings (OOP) and their applications. The contributing authors are well-recognized researchers and practitioners. The mathematical modelling and numerical solution aspects of each application case study are presented in sufficient detail. A broad range of OOP problems are discussed: these include various specific and non-standard container loading and object packing problems, as well as the stowing of hazardous and other materials on container ships, data centre resource management, automotive engineering design, space station logistic support, cutting and packing problems with placement constraints, the optimal design of LED street lighting, robust sensor deployment strategies, spatial scheduling problems, and graph coloring models and metaheuristics for packing applications. Novel points of view related to model development and to computational nonlinear, global, mixed integer optimization and heuristic st...

  7. Submodular functions and optimization

    CERN Document Server

    Fujishige, Satoru

    2005-01-01

    It has widely been recognized that submodular functions play essential roles in efficiently solvable combinatorial optimization problems. Since the publication of the 1st edition of this book fifteen years ago, submodular functions have been showing further increasing importance in optimization, combinatorics, discrete mathematics, algorithmic computer science, and algorithmic economics, and there have been made remarkable developments of theory and algorithms in submodular functions. The 2nd edition of the book supplements the 1st edition with a lot of remarks and with new two chapters: "Submodular Function Minimization" and "Discrete Convex Analysis." The present 2nd edition is still a unique book on submodular functions, which is essential to students and researchers interested in combinatorial optimization, discrete mathematics, and discrete algorithms in the fields of mathematics, operations research, computer science, and economics. Key features: - Self-contained exposition of the theory of submodular ...

  8. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  9. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  10. Optimal Power Flow Pursuit

    Energy Technology Data Exchange (ETDEWEB)

    Dall' Anese, Emiliano; Simonetto, Andrea

    2018-03-01

    This paper considers distribution networks featuring inverter-interfaced distributed energy resources, and develops distributed feedback controllers that continuously drive the inverter output powers to solutions of AC optimal power flow (OPF) problems. Particularly, the controllers update the power setpoints based on voltage measurements as well as given (time-varying) OPF targets, and entail elementary operations implementable onto low-cost microcontrollers that accompany power-electronics interfaces of gateways and inverters. The design of the control framework is based on suitable linear approximations of the AC power-flow equations as well as Lagrangian regularization methods. Convergence and OPF-target tracking capabilities of the controllers are analytically established. Overall, the proposed method allows to bypass traditional hierarchical setups where feedback control and optimization operate at distinct time scales, and to enable real-time optimization of distribution systems.

  11. Filters in topology optimization

    DEFF Research Database (Denmark)

    Bourdin, Blaise

    1999-01-01

    In this article, a modified (``filtered'') version of the minimum compliance topology optimization problem is studied. The direct dependence of the material properties on its pointwise density is replaced by a regularization of the density field using a convolution operator. In this setting...... it is possible to establish the existence of solutions. Moreover, convergence of an approximation by means of finite elements can be obtained. This is illustrated through some numerical experiments. The ``filtering'' technique is also shown to cope with two important numerical problems in topology optimization...

  12. Wind farm design optimization

    Energy Technology Data Exchange (ETDEWEB)

    Carreau, Michel; Morgenroth, Michael; Belashov, Oleg; Mdimagh, Asma; Hertz, Alain; Marcotte, Odile

    2010-09-15

    Innovative numerical computer tools have been developed to streamline the estimation, the design process and to optimize the Wind Farm Design with respect to the overall return on investment. The optimization engine can find the collector system layout automatically which provide a powerful tool to quickly study various alternative taking into account more precisely various constraints or factors that previously would have been too costly to analyze in details with precision. Our Wind Farm Tools have evolved through numerous projects and created value for our clients yielding Wind Farm projects with projected higher returns.

  13. Landscape encodings enhance optimization.

    Directory of Open Access Journals (Sweden)

    Konstantin Klemm

    Full Text Available Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state.

  14. An introduction to optimization

    CERN Document Server

    Chong, Edwin K P

    2013-01-01

    Praise for the Third Edition "". . . guides and leads the reader through the learning path . . . [e]xamples are stated very clearly and the results are presented with attention to detail.""  -MAA Reviews  Fully updated to reflect new developments in the field, the Fourth Edition of Introduction to Optimization fills the need for accessible treatment of optimization theory and methods with an emphasis on engineering design. Basic definitions and notations are provided in addition to the related fundamental background for linear algebra, geometry, and calculus.  This new

  15. Surveillance test interval optimization

    International Nuclear Information System (INIS)

    Cepin, M.; Mavko, B.

    1995-01-01

    Technical specifications have been developed on the bases of deterministic analyses, engineering judgment, and expert opinion. This paper introduces our risk-based approach to surveillance test interval (STI) optimization. This approach consists of three main levels. The first level is the component level, which serves as a rough estimation of the optimal STI and can be calculated analytically by a differentiating equation for mean unavailability. The second and third levels give more representative results. They take into account the results of probabilistic risk assessment (PRA) calculated by a personal computer (PC) based code and are based on system unavailability at the system level and on core damage frequency at the plant level

  16. Disturbance by optimal discrimination

    Science.gov (United States)

    Kawakubo, Ryûitirô; Koike, Tatsuhiko

    2018-03-01

    We discuss the disturbance by measurements which unambiguously discriminate between given candidate states. We prove that such an optimal measurement necessarily changes distinguishable states indistinguishable when the inconclusive outcome is obtained. The result was previously shown by Chefles [Phys. Lett. A 239, 339 (1998), 10.1016/S0375-9601(98)00064-4] under restrictions on the class of quantum measurements and on the definition of optimality. Our theorems remove these restrictions and are also applicable to infinitely many candidate states. Combining with our previous results, one can obtain concrete mathematical conditions for the resulting states. The method may have a wide variety of applications in contexts other than state discrimination.

  17. Distributed Optimization System

    Science.gov (United States)

    Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

    2004-11-30

    A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

  18. ATHENA optimized coating design

    DEFF Research Database (Denmark)

    Ferreira, Desiree Della Monica; Christensen, Finn Erland; Jakobsen, Anders Clemen

    2012-01-01

    The optimization of coating design for the ATHENA mission si described and the possibility of increasing the telescope effective area in the range between 0.1 and 10 keV is investigated. An independent computation of the on-axis effective area based on the mirror design of ATHENA is performed...... in order to review the current coating baseline. The performance of several material combinations, considering a simple bi-layer, simple multilayer and linear graded multilayer coatings are tested and simulation of the mirror performance considering both the optimized coating design and the coating...

  19. Satellite image collection optimization

    Science.gov (United States)

    Martin, William

    2002-09-01

    Imaging satellite systems represent a high capital cost. Optimizing the collection of images is critical for both satisfying customer orders and building a sustainable satellite operations business. We describe the functions of an operational, multivariable, time dynamic optimization system that maximizes the daily collection of satellite images. A graphical user interface allows the operator to quickly see the results of what if adjustments to an image collection plan. Used for both long range planning and daily collection scheduling of Space Imaging's IKONOS satellite, the satellite control and tasking (SCT) software allows collection commands to be altered up to 10 min before upload to the satellite.

  20. Constrained Optimal Transport

    Science.gov (United States)

    Ekren, Ibrahim; Soner, H. Mete

    2018-03-01

    The classical duality theory of Kantorovich (C R (Doklady) Acad Sci URSS (NS) 37:199-201, 1942) and Kellerer (Z Wahrsch Verw Gebiete 67(4):399-432, 1984) for classical optimal transport is generalized to an abstract framework and a characterization of the dual elements is provided. This abstract generalization is set in a Banach lattice X with an order unit. The problem is given as the supremum over a convex subset of the positive unit sphere of the topological dual of X and the dual problem is defined on the bi-dual of X. These results are then applied to several extensions of the classical optimal transport.

  1. Practical methods of optimization

    CERN Document Server

    Fletcher, R

    2013-01-01

    Fully describes optimization methods that are currently most valuable in solving real-life problems. Since optimization has applications in almost every branch of science and technology, the text emphasizes their practical aspects in conjunction with the heuristics useful in making them perform more reliably and efficiently. To this end, it presents comparative numerical studies to give readers a feel for possibile applications and to illustrate the problems in assessing evidence. Also provides theoretical background which provides insights into how methods are derived. This edition offers rev

  2. Advanced backend optimization

    CERN Document Server

    Touati, Sid

    2014-01-01

    This book is a summary of more than a decade of research in the area of backend optimization. It contains the latest fundamental research results in this field. While existing books are often more oriented toward Masters students, this book is aimed more towards professors and researchers as it contains more advanced subjects.It is unique in the sense that it contains information that has not previously been covered by other books in the field, with chapters on phase ordering in optimizing compilation; register saturation in instruction level parallelism; code size reduction for software pipe

  3. Analytical methods of optimization

    CERN Document Server

    Lawden, D F

    2006-01-01

    Suitable for advanced undergraduates and graduate students, this text surveys the classical theory of the calculus of variations. It takes the approach most appropriate for applications to problems of optimizing the behavior of engineering systems. Two of these problem areas have strongly influenced this presentation: the design of the control systems and the choice of rocket trajectories to be followed by terrestrial and extraterrestrial vehicles.Topics include static systems, control systems, additional constraints, the Hamilton-Jacobi equation, and the accessory optimization problem. Prereq

  4. Optimization of dental implantation

    Science.gov (United States)

    Dol, Aleksandr V.; Ivanov, Dmitriy V.

    2017-02-01

    Modern dentistry can not exist without dental implantation. This work is devoted to study of the "bone-implant" system and to optimization of dental prostheses installation. Modern non-invasive methods such as MRI an 3D-scanning as well as numerical calculations and 3D-prototyping allow to optimize all of stages of dental prosthetics. An integrated approach to the planning of implant surgery can significantly reduce the risk of complications in the first few days after treatment, and throughout the period of operation of the prosthesis.

  5. Towards Optimal PDE Simulations

    International Nuclear Information System (INIS)

    Keyes, David

    2009-01-01

    The Terascale Optimal PDE Solvers (TOPS) Integrated Software Infrastructure Center (ISIC) was created to develop and implement algorithms and support scientific investigations performed by DOE-sponsored researchers. These simulations often involve the solution of partial differential equations (PDEs) on terascale computers. The TOPS Center researched, developed and deployed an integrated toolkit of open-source, optimal complexity solvers for the nonlinear partial differential equations that arise in many DOE application areas, including fusion, accelerator design, global climate change and reactive chemistry. The algorithms created as part of this project were also designed to reduce current computational bottlenecks by orders of magnitude on terascale computers, enabling scientific simulation on a scale heretofore impossible.

  6. Landscape Encodings Enhance Optimization

    Science.gov (United States)

    Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

    2012-01-01

    Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

  7. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available -of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study... for the following equation: n∑ i=r ( n i ) pi(1− p)n−i = 0.95 . (1) Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results METHODS (cont. . . ): FITNESS FUNCTION...

  8. Terascale Optimal PDE Simulations

    Energy Technology Data Exchange (ETDEWEB)

    David Keyes

    2009-07-28

    The Terascale Optimal PDE Solvers (TOPS) Integrated Software Infrastructure Center (ISIC) was created to develop and implement algorithms and support scientific investigations performed by DOE-sponsored researchers. These simulations often involve the solution of partial differential equations (PDEs) on terascale computers. The TOPS Center researched, developed and deployed an integrated toolkit of open-source, optimal complexity solvers for the nonlinear partial differential equations that arise in many DOE application areas, including fusion, accelerator design, global climate change and reactive chemistry. The algorithms created as part of this project were also designed to reduce current computational bottlenecks by orders of magnitude on terascale computers, enabling scientific simulation on a scale heretofore impossible.

  9. Honing process optimization algorithms

    Science.gov (United States)

    Kadyrov, Ramil R.; Charikov, Pavel N.; Pryanichnikova, Valeria V.

    2018-03-01

    This article considers the relevance of honing processes for creating high-quality mechanical engineering products. The features of the honing process are revealed and such important concepts as the task for optimization of honing operations, the optimal structure of the honing working cycles, stepped and stepless honing cycles, simulation of processing and its purpose are emphasized. It is noted that the reliability of the mathematical model determines the quality parameters of the honing process control. An algorithm for continuous control of the honing process is proposed. The process model reliably describes the machining of a workpiece in a sufficiently wide area and can be used to operate the CNC machine CC743.

  10. Optimization Modeling with Spreadsheets

    CERN Document Server

    Baker, Kenneth R

    2011-01-01

    This introductory book on optimization (mathematical programming) includes coverage on linear programming, nonlinear programming, integer programming and heuristic programming; as well as an emphasis on model building using Excel and Solver.  The emphasis on model building (rather than algorithms) is one of the features that makes this book distinctive. Most books devote more space to algorithmic details than to formulation principles. These days, however, it is not necessary to know a great deal about algorithms in order to apply optimization tools, especially when relying on the sp

  11. Optimally cloned binary coherent states

    DEFF Research Database (Denmark)

    Mueller, C. R.; Leuchs, G.; Marquardt, Ch

    2017-01-01

    their quantum-optimal clones. We analyze the Wigner function and the cumulants of the clones, and we conclude that optimal cloning of binary coherent states requires a nonlinearity above second order. We propose several practical and near-optimal cloning schemes and compare their cloning fidelity to the optimal...

  12. HEURISTIC APPROACHES FOR PORTFOLIO OPTIMIZATION

    OpenAIRE

    Manfred Gilli, Evis Kellezi

    2000-01-01

    The paper first compares the use of optimization heuristics to the classical optimization techniques for the selection of optimal portfolios. Second, the heuristic approach is applied to problems other than those in the standard mean-variance framework where the classical optimization fails.

  13. Bayesian optimization for materials science

    CERN Document Server

    Packwood, Daniel

    2017-01-01

    This book provides a short and concise introduction to Bayesian optimization specifically for experimental and computational materials scientists. After explaining the basic idea behind Bayesian optimization and some applications to materials science in Chapter 1, the mathematical theory of Bayesian optimization is outlined in Chapter 2. Finally, Chapter 3 discusses an application of Bayesian optimization to a complicated structure optimization problem in computational surface science. Bayesian optimization is a promising global optimization technique that originates in the field of machine learning and is starting to gain attention in materials science. For the purpose of materials design, Bayesian optimization can be used to predict new materials with novel properties without extensive screening of candidate materials. For the purpose of computational materials science, Bayesian optimization can be incorporated into first-principles calculations to perform efficient, global structure optimizations. While re...

  14. Optimal Market Design

    NARCIS (Netherlands)

    Boone, J.; Goeree, J.K.

    2010-01-01

    This paper introduces three methodological advances to study the optimal design of static and dynamic markets. First, we apply a mechanism design approach to characterize all incentive-compatible market equilibria. Second, we conduct a normative analysis, i.e. we evaluate alternative competition and

  15. Optimal Ski Jump

    Science.gov (United States)

    Rebilas, Krzysztof

    2013-01-01

    Consider a skier who goes down a takeoff ramp, attains a speed "V", and jumps, attempting to land as far as possible down the hill below (Fig. 1). At the moment of takeoff the angle between the skier's velocity and the horizontal is [alpha]. What is the optimal angle [alpha] that makes the jump the longest possible for the fixed magnitude of the…

  16. Danfoss: Scroll Optimization

    DEFF Research Database (Denmark)

    Gravesen, Jens; Henriksen, Christian; Howell, Peter

    1998-01-01

    The standard scroll compressor consists of two identical spirals (circle involutes) running inside each other.The task from Danfoss was to investigate how a change in the basic geometry of the scrolss and the orbit influence the compressor performnce and efficiency, and then try to optimize...

  17. Optimization of Pipe Networks

    DEFF Research Database (Denmark)

    Hansen, C. T.; Madsen, Kaj; Nielsen, Hans Bruun

    1991-01-01

    algorithm using successive linear programming is presented. The performance of the algorithm is illustrated by optimizing a network with 201 pipes and 172 nodes. It is concluded that the new algorithm seems to be very efficient and stable, and that it always finds a solution with a cost near the best...

  18. Topology optimization approaches

    DEFF Research Database (Denmark)

    Sigmund, Ole; Maute, Kurt

    2013-01-01

    Topology optimization has undergone a tremendous development since its introduction in the seminal paper by Bendsøe and Kikuchi in 1988. By now, the concept is developing in many different directions, including “density”, “level set”, “topological derivative”, “phase field”, “evolutionary...

  19. Slope constrained Topology Optimization

    DEFF Research Database (Denmark)

    Petersson, J.; Sigmund, Ole

    1998-01-01

    The problem of minimum compliance topology optimization of an elastic continuum is considered. A general continuous density-energy relation is assumed, including variable thickness sheet models and artificial power laws. To ensure existence of solutions, the design set is restricted by enforcing...

  20. Wind turbine pitch optimization

    DEFF Research Database (Denmark)

    Biegel, Benjamin; Juelsgaard, Morten; Stoustrup, Jakob

    2011-01-01

    for maximizing power production while simultaneously minimizing fatigue loads. In this paper, we show how this problem can be approximately solved using convex optimization. When there is full knowledge of the wind field, numerical simulations show that force and torque RMS variation can be reduced by over 96...

  1. Fourier Series Optimization Opportunity

    Science.gov (United States)

    Winkel, Brian

    2008-01-01

    This note discusses the introduction of Fourier series as an immediate application of optimization of a function of more than one variable. Specifically, it is shown how the study of Fourier series can be motivated to enrich a multivariable calculus class. This is done through discovery learning and use of technology wherein students build the…

  2. Advanced BDD optimization

    CERN Document Server

    Ebendt, Rudiger; Drechsler, Rolf

    2005-01-01

    BDD and SAT are major concepts in VLSI CADNew objective functions for design space exploration require new algorithms for BDD optimizationLatest trend: fusion of the concepts BDD and SATMajor impulses come from Artificial Intelligence (AI)Unifying view, transfers the latest theoretical insights into practical applications.

  3. Fundamentals and Optimal Institutions

    DEFF Research Database (Denmark)

    Gonzalez-Eiras, Martin; Harmon, Nikolaj Arpe; Rossi, Martín

    2016-01-01

    of regulatory institutions such as revenue sharing, salary caps or luxury taxes. We show, theoretically and empirically, that these large differences in adopted institutions can be rationalized as optimal responses to differences in the fundamental characteristics of the sports being played. This provides...

  4. Optimizing clozapine treatment

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Damkier, P; Lublin, Henrik

    2011-01-01

    Clozapine treatment remains the gold standard for treatment-resistant schizophrenia, but treatment with clozapine is associated with several side-effects that complicate the use of the drug. This clinical overview aims to provide psychiatrists with knowledge about how to optimize clozapine...... treatment. Relevant strategies for reducing side-effects and increasing the likelihood of response are discussed....

  5. Toward Optimal Transport Networks

    Science.gov (United States)

    Alexandrov, Natalia; Kincaid, Rex K.; Vargo, Erik P.

    2008-01-01

    Strictly evolutionary approaches to improving the air transport system a highly complex network of interacting systems no longer suffice in the face of demand that is projected to double or triple in the near future. Thus evolutionary approaches should be augmented with active design methods. The ability to actively design, optimize and control a system presupposes the existence of predictive modeling and reasonably well-defined functional dependences between the controllable variables of the system and objective and constraint functions for optimization. Following recent advances in the studies of the effects of network topology structure on dynamics, we investigate the performance of dynamic processes on transport networks as a function of the first nontrivial eigenvalue of the network's Laplacian, which, in turn, is a function of the network s connectivity and modularity. The last two characteristics can be controlled and tuned via optimization. We consider design optimization problem formulations. We have developed a flexible simulation of network topology coupled with flows on the network for use as a platform for computational experiments.

  6. On optimal quadrature formulae

    Directory of Open Access Journals (Sweden)

    Lanzara Flavia

    2000-01-01

    Full Text Available A procedure to construct quadrature formulae which are exact for solutions of linear differential equations and are optimal in the sense of Sard is discussed. We give necessary and sufficient conditions under which such formulae do exist. Several formulae obtained by applying this method are considered and compared with well known formulae.

  7. Optimal Central Bank Transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.

    2008-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  8. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.

    2008-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  9. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.

    2010-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  10. Calculating Optimal Inventory Size

    Directory of Open Access Journals (Sweden)

    Ruby Perez

    2010-01-01

    Full Text Available The purpose of the project is to find the optimal value for the Economic Order Quantity Model and then use a lean manufacturing Kanban equation to find a numeric value that will minimize the total cost and the inventory size.

  11. Optimal decoupling controllers revisited

    Czech Academy of Sciences Publication Activity Database

    Kučera, Vladimír

    2013-01-01

    Roč. 42, č. 1 (2013), s. 1-16 ISSN 0324-8569 R&D Projects: GA TA ČR(CZ) TE01020197 Institutional support: RVO:67985556 Keywords : linear systems * fractional representations * decoupling control lers * stabilizing control lers * optimal control lers Subject RIV: BC - Control Systems Theory

  12. Optimalization of IGBT Communication

    Directory of Open Access Journals (Sweden)

    Pavol Spanik

    2002-01-01

    Full Text Available The paper presents IGBT switch off process in order to reduce power loss in the structure. The soft switching method using switch-off after current reduction is used. Process mentioned above is optimized to minimize the power loss that is determined by experiment. Results obtained in the experiment can be helpful in a converter and controller design process.

  13. Optimized tomography of observables

    International Nuclear Information System (INIS)

    D'Ariano, G.M.; Paris, G. A.

    1998-01-01

    Tomographic measurement of observables is revisited and an adaptive optimization of the kernel functions suggested. The method is based on the existence of a class of null functions, which have zero tomographic average for any state of radiation. The general procedure is illustrated, and application to relevant observables analyzed in details for coherent, squeezed and 'cat' states.(author)

  14. Optimal Aging and Death

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan; Strulik, Holger

    the representative consumer is subject to physiological aging. In modeling aging we draw on recent research in the fields of biology and medicine. The speed of the aging process, and thus the time of death, are endogenously determined by optimal health investments. We calibrate the model to US data and proceed...

  15. Spatiotemporal AED Location Optimization

    NARCIS (Netherlands)

    Chan, Timothy C.Y.; Sun, Christopher L.F.; Demirtas, Derya; Morrison, Laurie J.; Brooks, Steven C.

    2015-01-01

    Background: Mathematical optimization can be used to plan future AED placement to maximize out-of-hospital cardiac arrest (OHCA) coverage. Many public access AEDs are placed in locations without 24/7 access. AED coverage can be overestimated unless temporal availability is considered. Objective: To

  16. Minimalism and Optimality Theory

    NARCIS (Netherlands)

    Broekhuis, H.; Woolford, E.; den Dikken, M.

    2013-01-01

    This article discusses the relation between the minimalist program (MP) and optimality theory (OT) and will show that, contrary to popular belief, MP and OT are not inherently incompatible or competing frameworks/theories. Instead, we will show (i) that the two can well be seen as complementary

  17. Is Optimism Real?

    Science.gov (United States)

    Simmons, Joseph P.; Massey, Cade

    2012-01-01

    Is optimism real, or are optimistic forecasts just cheap talk? To help answer this question, we investigated whether optimistic predictions persist in the face of large incentives to be accurate. We asked National Football League football fans to predict the winner of a single game. Roughly half (the partisans) predicted a game involving their…

  18. Potentialitet og optimering

    DEFF Research Database (Denmark)

    Hamre, Bjørn

    . Afhandlingen kan både ses som et bidrag til eksisterende governmentality studier inden for uddannelse og som et bidrag til forskning i specialpædagogik. Optimering ses som en type rationalitetsform og magtudøvelse, der defi nerer problemforståelser i nutiden og sætter et skel mellem den adfærd, der inkluderes...

  19. Optimal Packed String Matching

    DEFF Research Database (Denmark)

    Ben-Kiki, Oren; Bille, Philip; Breslauer, Dany

    2011-01-01

    In the packed string matching problem, each machine word accommodates – characters, thus an n-character text occupies n/– memory words. We extend the Crochemore-Perrin constantspace O(n)-time string matching algorithm to run in optimal O(n/–) time and even in real-time, achieving a factor – speed...

  20. Optimal human capital policies

    Czech Academy of Sciences Publication Activity Database

    Boháček, Radim; Kapička, M.

    2008-01-01

    Roč. 55, č. 1 (2008), s. 1-16 ISSN 0304-3932 Institutional research plan: CEZ:AV0Z70850503 Keywords : dynamic optimal taxation * income taxation Subject RIV: AH - Economics Impact factor: 1.429, year: 2008

  1. Towards Optimal Transport Networks

    Directory of Open Access Journals (Sweden)

    Erik P. Vargo

    2010-08-01

    Full Text Available Our ultimate goal is to design transportation net- works whose dynamic performance metrics (e.g. pas- senger throughput, passenger delay, and insensitivity to weather disturbances are optimized. Here the fo- cus is on optimizing static features of the network that are known to directly affect the network dynamics. First, we present simulation results which support a connection between maximizing the first non-trivial eigenvalue of a network's Laplacian and superior air- port network performance. Then, we explore the ef- fectiveness of a tabu search heuristic for optimizing this metric by comparing experimental results to the- oretical upper bounds. We also consider generating upper bounds on a network's algebraic connectivity via the solution of semidefinite programming (SDP relaxations. A modification of an existing subgraph extraction algorithm is implemented to explore the underlying regional structures in the U.S. airport net- work, with the hope that the resulting localized struc- tures can be optimized independently and reconnected via a "backbone" network to achieve superior network performance.

  2. Optimal Quadratic Programming Algorithms

    CERN Document Server

    Dostal, Zdenek

    2009-01-01

    Quadratic programming (QP) is one technique that allows for the optimization of a quadratic function in several variables in the presence of linear constraints. This title presents various algorithms for solving large QP problems. It is suitable as an introductory text on quadratic programming for graduate students and researchers

  3. Pareto-optimal alloys

    DEFF Research Database (Denmark)

    Bligaard, Thomas; Johannesson, Gisli Holmar; Ruban, Andrei

    2003-01-01

    Large databases that can be used in the search for new materials with specific properties remain an elusive goal in materials science. The problem is complicated by the fact that the optimal material for a given application is usually a compromise between a number of materials properties and the ......Large databases that can be used in the search for new materials with specific properties remain an elusive goal in materials science. The problem is complicated by the fact that the optimal material for a given application is usually a compromise between a number of materials properties...... and the cost. In this letter we present a database consisting of the lattice parameters, bulk moduli, and heats of formation for over 64 000 ordered metallic alloys, which has been established by direct first-principles density-functional-theory calculations. Furthermore, we use a concept from economic theory......, the Pareto-optimal set, to determine optimal alloy solutions for the compromise between low compressibility, high stability, and cost....

  4. Optimal fault signal estimation

    NARCIS (Netherlands)

    Stoorvogel, Antonie Arij; Niemann, H.H.; Saberi, A.; Sannuti, P.

    2002-01-01

    We consider here both fault identification and fault signal estimation. Regarding fault identification, we seek either exact or almost fault identification. On the other hand, regarding fault signal estimation, we seek either $H_2$ optimal, $H_2$ suboptimal or Hinfinity suboptimal estimation. By

  5. Optimization of accelerator control

    International Nuclear Information System (INIS)

    Vasiljev, N.D.; Mozin, I.V.; Shelekhov, V.A.; Efremov, D.V.

    1992-01-01

    Expensive exploitation of charged particle accelerators is inevitably concerned with requirements of effectively obtaining of the best characteristics of accelerated beams for physical experiments. One of these characteristics is intensity. Increase of intensity is hindered by a number of effects, concerned with the influence of the volume charge field on a particle motion dynamics in accelerator's chamber. However, ultimate intensity, determined by a volume charge, is almost not achieved for the most of the operating accelerators. This fact is caused by losses of particles during injection, at the initial stage of acceleration and during extraction. These losses are caused by deviations the optimal from real characteristics of the accelerating and magnetic system. This is due to a number of circumstances, including technological tolerances on structural elements of systems, influence of measuring and auxiliary equipment and beam consumers' installations, placed in the closed proximity to magnets, and instability in operation of technological systems of accelerator. Control task consists in compensation of deviations of characteristics of magnetic and electric fields by optimal selection of control actions. As for technical means, automatization of modern accelerators allows to solve optimal control problems in real time. Therefore, the report is devoted to optimal control methods and experimental results. (J.P.N.)

  6. Optimal crowd evacuation

    NARCIS (Netherlands)

    Hoogendoorn, S.P.; Daamen, W.; Duives, D.C.; Van Wageningen-Kessels, F.L.M.

    2013-01-01

    This paper deals with the optimal allocation of routes, destination, and departure times to members of a crowd, for instance in case of an evacuation or another hazardous situation in which the people need to leave the area as quickly as possible. The generic approach minimizes the evacuation times,

  7. Optimal GENCO bidding strategy

    Science.gov (United States)

    Gao, Feng

    Electricity industries worldwide are undergoing a period of profound upheaval. The conventional vertically integrated mechanism is being replaced by a competitive market environment. Generation companies have incentives to apply novel technologies to lower production costs, for example: Combined Cycle units. Economic dispatch with Combined Cycle units becomes a non-convex optimization problem, which is difficult if not impossible to solve by conventional methods. Several techniques are proposed here: Mixed Integer Linear Programming, a hybrid method, as well as Evolutionary Algorithms. Evolutionary Algorithms share a common mechanism, stochastic searching per generation. The stochastic property makes evolutionary algorithms robust and adaptive enough to solve a non-convex optimization problem. This research implements GA, EP, and PS algorithms for economic dispatch with Combined Cycle units, and makes a comparison with classical Mixed Integer Linear Programming. The electricity market equilibrium model not only helps Independent System Operator/Regulator analyze market performance and market power, but also provides Market Participants the ability to build optimal bidding strategies based on Microeconomics analysis. Supply Function Equilibrium (SFE) is attractive compared to traditional models. This research identifies a proper SFE model, which can be applied to a multiple period situation. The equilibrium condition using discrete time optimal control is then developed for fuel resource constraints. Finally, the research discusses the issues of multiple equilibria and mixed strategies, which are caused by the transmission network. Additionally, an advantage of the proposed model for merchant transmission planning is discussed. A market simulator is a valuable training and evaluation tool to assist sellers, buyers, and regulators to understand market performance and make better decisions. A traditional optimization model may not be enough to consider the distributed

  8. Power system optimization

    International Nuclear Information System (INIS)

    Bogdan, Zeljko; Cehil, Mislav

    2007-01-01

    Long-term gas purchase contracts usually determine delivery and payment for gas on the regular hourly basis, independently of demand side consumption. In order to use fuel gas in an economically viable way, optimization of gas distribution for covering consumption must be introduced. In this paper, a mathematical model of the electric utility system which is used for optimization of gas distribution over electric generators is presented. The utility system comprises installed capacity of 1500 MW of thermal power plants, 400 MW of combined heat and power plants, 330 MW of a nuclear power plant and 1600 MW of hydro power plants. Based on known demand curve the optimization model selects plants according to the prescribed criteria. Firstly it engages run-of-river hydro plants, then the public cogeneration plants, the nuclear plant and thermal power plants. Storage hydro plants are used for covering peak load consumption. In case of shortage of installed capacity, the cross-border purchase is allowed. Usage of dual fuel equipment (gas-oil), which is available in some thermal plants, is also controlled by the optimization procedure. It is shown that by using such a model it is possible to properly plan the amount of fuel gas which will be contracted. The contracted amount can easily be distributed over generators efficiently and without losses (no breaks in delivery). The model helps in optimizing of fuel gas-oil ratio for plants with combined burners and enables planning of power plants overhauls over a year in a viable and efficient way. (author)

  9. (Too) optimistic about optimism: the belief that optimism improves performance.

    Science.gov (United States)

    Tenney, Elizabeth R; Logg, Jennifer M; Moore, Don A

    2015-03-01

    A series of experiments investigated why people value optimism and whether they are right to do so. In Experiments 1A and 1B, participants prescribed more optimism for someone implementing decisions than for someone deliberating, indicating that people prescribe optimism selectively, when it can affect performance. Furthermore, participants believed optimism improved outcomes when a person's actions had considerable, rather than little, influence over the outcome (Experiment 2). Experiments 3 and 4 tested the accuracy of this belief; optimism improved persistence, but it did not improve performance as much as participants expected. Experiments 5A and 5B found that participants overestimated the relationship between optimism and performance even when their focus was not on optimism exclusively. In summary, people prescribe optimism when they believe it has the opportunity to improve the chance of success-unfortunately, people may be overly optimistic about just how much optimism can do. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  10. Group leaders optimization algorithm

    Science.gov (United States)

    Daskin, Anmer; Kais, Sabre

    2011-03-01

    We present a new global optimization algorithm in which the influence of the leaders in social groups is used as an inspiration for the evolutionary technique which is designed into a group architecture. To demonstrate the efficiency of the method, a standard suite of single and multi-dimensional optimization functions along with the energies and the geometric structures of Lennard-Jones clusters are given as well as the application of the algorithm on quantum circuit design problems. We show that as an improvement over previous methods, the algorithm scales as N 2.5 for the Lennard-Jones clusters of N-particles. In addition, an efficient circuit design is shown for a two-qubit Grover search algorithm which is a quantum algorithm providing quadratic speedup over the classical counterpart.

  11. Radiological assessment and optimization

    International Nuclear Information System (INIS)

    Zeevaert, T.; Sohier, A.

    1998-01-01

    The objectives of SCK-CEN's research in the field of radiological assessment and optimization are (1) to implement ALARA principles in activities with radiological consequences; (2) to develop methodologies for radiological optimization in decision-aiding; (3) to improve methods to assess in real time the radiological hazards in the environment in case of an accident; (4) to develop methods and programmes to assist decision-makers during a nuclear emergency; (5) to support the policy of radioactive waste management authorities in the field of radiation protection; (6) to investigate computer codes in the area of multi criteria analysis; (7) to organise courses on off-site emergency response to nuclear accidents. Main achievements in these areas for 1997 are summarised

  12. Optimal Product Placement.

    Science.gov (United States)

    Hsu, Chia-Ling; Matta, Rafael; Popov, Sergey V; Sogo, Takeharu

    2017-01-01

    We model a market, such as an online software market, in which an intermediary connects sellers and buyers by displaying sellers' products. With two vertically-differentiated products, an intermediary can place either: (1) one product, not necessarily the better one, on the first page, and the other hidden on the second page; or (2) both products on the first page. We show that it can be optimal for the intermediary to obfuscate a product-possibly the better one-since this weakens price competition and allows the sellers to extract a greater surplus from buyers; however, it is not socially optimal. The choice of which one to obfuscate depends on the distribution of search costs.

  13. Optimization by record dynamics

    DEFF Research Database (Denmark)

    Barettin, Daniele; Sibani, Paolo

    2014-01-01

    Large dynamical changes in thermalizing glassy systems are triggered by trajectories crossing record sized barriers, a behavior revealing the presence of a hierarchical structure in configuration space. The observation is here turned into a novel local search optimization algorithm dubbed record...... dynamics optimization,or RDO. RDO uses the Metropolis rule to accept or reject candidate solutions depending on the value of a parameter akin to the temperature and minimizes the cost function of the problem at hand through cycles where its ‘temperature’ is raised and subsequently decreased in order......), is applied to the same problem as a benchmark. RDO and PT turn out to produce solutions of similar quality for similar numerical effort, but RDO is simpler to program and additionally yields geometrical information on the system’s configuration space which is of interest in many applications. In particular...

  14. Combinatorial optimization games

    Energy Technology Data Exchange (ETDEWEB)

    Deng, X. [York Univ., North York, Ontario (Canada); Ibaraki, Toshihide; Nagamochi, Hiroshi [Kyoto Univ. (Japan)

    1997-06-01

    We introduce a general integer programming formulation for a class of combinatorial optimization games, which immediately allows us to improve the algorithmic result for finding amputations in the core (an important solution concept in cooperative game theory) of the network flow game on simple networks by Kalai and Zemel. An interesting result is a general theorem that the core for this class of games is nonempty if and only if a related linear program has an integer optimal solution. We study the properties for this mathematical condition to hold for several interesting problems, and apply them to resolve algorithmic and complexity issues for their cores along the line as put forward in: decide whether the core is empty; if the core is empty, find an imputation in the core; given an imputation x, test whether x is in the core. We also explore the properties of totally balanced games in this succinct formulation of cooperative games.

  15. DIRAC optimized workload management

    CERN Document Server

    Paterson, S K

    2008-01-01

    The LHCb DIRAC Workload and Data Management System employs advanced optimization techniques in order to dynamically allocate resources. The paradigms realized by DIRAC, such as late binding through the Pilot Agent approach, have proven to be highly successful. For example, this has allowed the principles of workload management to be applied not only at the time of user job submission to the Grid but also to optimize the use of computing resources once jobs have been acquired. Along with the central application of job priorities, DIRAC minimizes the system response time for high priority tasks. This paper will describe the recent developments to support Monte Carlo simulation, data processing and distributed user analysis in a consistent way across disparate compute resources including individual PCs, local batch systems, and the Worldwide LHC Computing Grid. The Grid environment is inherently unpredictable and whilst short-term studies have proven to deliver high job efficiencies, the system performance over ...

  16. Optimal Responsible Investment

    DEFF Research Database (Denmark)

    Jessen, Pernille

    Numerous institutions are now engaged in Socially Responsible Investment or have signed the "UN Principles for Responsible Investment". Retail investors, however, are still lacking behind. This is peculiar since the sector constitutes key stakeholders in environmental, social and governmental...... standards. This paper considers optimal responsible investment for a small retail investor. It extends conventional portfolio theory by allowing for a personal-value based investment decision. Preferences for responsibility are defined in the framework of mean-variance analysis and an optimal responsible...... investment model identified. Implications of the altered investment problem are investigated when the dynamics between portfolio risk, expected return and responsibility is considered. Relying on the definition of a responsible investor, it is shown how superior investment opportunities can emerge when...

  17. Optimizing well intervention routes

    Energy Technology Data Exchange (ETDEWEB)

    Paiva, Ronaldo O. [PETROBRAS S.A., Vitoria, ES (Brazil); Schiozer, Denis J.; Bordalo, Sergio N. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Mecanica. Centro de Estudo do Petroleo (CEPETRO)]. E-mail: denis@dep.fem.unicamp.br; bordalo@dep.fem.unicamp.br

    2000-07-01

    This work presents a method for optimizing the itinerary of work over rigs, i.e., the search for the route of minimum total cost, and demonstrates the importance of the dynamics of reservoir behaviour. The total cost of a route includes the rig expenses (transport, assembly and operation), which are functions of time and distances, plus the losses of revenue in wells waiting for the rig, which are also dependent of time. A reservoir simulator is used to evaluate the monetary influence of the well shutdown on the present value of the production curve. Finally, search algorithms are employed to determine the route of minimal cost. The Simulated Annealing algorithm was also successful in optimizing the distribution of a list of wells among different work over rigs. The rational approach presented here is recommended for management teams as a standard procedure to define the priority of wells scheduled for work over. (author)

  18. Optimally frugal foraging

    Science.gov (United States)

    Bénichou, O.; Bhat, U.; Krapivsky, P. L.; Redner, S.

    2018-02-01

    We introduce the frugal foraging model in which a forager performs a discrete-time random walk on a lattice in which each site initially contains S food units. The forager metabolizes one unit of food at each step and starves to death when it last ate S steps in the past. Whenever the forager eats, it consumes all food at its current site and this site remains empty forever (no food replenishment). The crucial property of the forager is that it is frugal and eats only when encountering food within at most k steps of starvation. We compute the average lifetime analytically as a function of the frugality threshold and show that there exists an optimal strategy, namely, an optimal frugality threshold k* that maximizes the forager lifetime.

  19. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available prospective map are the weights-of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote.... . . ): FITNESS FUNCTION φWMSD+V(Sn) = λ N(A) ∑ −→x ∈A P(−→x ) ∣ ∣ ∣ ∣−→x −QSn( −→x ) ∣ ∣ ∣ ∣ +(1− λ)s2(OSn) , (2) where QSn( −→x ) is the location vector of an optimal exploration focal point in Sn nearest to −→x , and s2(OSn) is the variance...

  20. Multilevel geometry optimization

    Science.gov (United States)

    Rodgers, Jocelyn M.; Fast, Patton L.; Truhlar, Donald G.

    2000-02-01

    Geometry optimization has been carried out for three test molecules using six multilevel electronic structure methods, in particular Gaussian-2, Gaussian-3, multicoefficient G2, multicoefficient G3, and two multicoefficient correlation methods based on correlation-consistent basis sets. In the Gaussian-2 and Gaussian-3 methods, various levels are added and subtracted with unit coefficients, whereas the multicoefficient Gaussian-x methods involve noninteger parameters as coefficients. The multilevel optimizations drop the average error in the geometry (averaged over the 18 cases) by a factor of about two when compared to the single most expensive component of a given multilevel calculation, and in all 18 cases the accuracy of the atomization energy for the three test molecules improves; with an average improvement of 16.7 kcal/mol.

  1. Multilevel geometry optimization

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, Jocelyn M. [Department of Chemistry and Supercomputer Institute, University of Minnesota, Minneapolis, Minnesota 55455-0431 (United States); Fast, Patton L. [Department of Chemistry and Supercomputer Institute, University of Minnesota, Minneapolis, Minnesota 55455-0431 (United States); Truhlar, Donald G. [Department of Chemistry and Supercomputer Institute, University of Minnesota, Minneapolis, Minnesota 55455-0431 (United States)

    2000-02-15

    Geometry optimization has been carried out for three test molecules using six multilevel electronic structure methods, in particular Gaussian-2, Gaussian-3, multicoefficient G2, multicoefficient G3, and two multicoefficient correlation methods based on correlation-consistent basis sets. In the Gaussian-2 and Gaussian-3 methods, various levels are added and subtracted with unit coefficients, whereas the multicoefficient Gaussian-x methods involve noninteger parameters as coefficients. The multilevel optimizations drop the average error in the geometry (averaged over the 18 cases) by a factor of about two when compared to the single most expensive component of a given multilevel calculation, and in all 18 cases the accuracy of the atomization energy for the three test molecules improves; with an average improvement of 16.7 kcal/mol. (c) 2000 American Institute of Physics.

  2. Real time production optimization

    Energy Technology Data Exchange (ETDEWEB)

    Saputelli, Luigi; Otavio, Joao; Araujo, Turiassu; Escorcia, Alvaro [Halliburton, Houston, TX (United States). Landmark Division

    2004-07-01

    Production optimization encompasses various activities of measuring, analyzing, modeling, prioritizing and implementing actions to enhance productivity of a field. We present a state-of-the-art framework for optimizing production on a continuous basis as new sensor data is acquired in real time. Permanently acquired data is modeled and analyzed in order to create predictive models. A model based control strategy is used to regulate well and field instrumentation. The optimum field operating point, which changes with time, satisfies the maximum economic return. This work is a starting point for further development in automatic, intelligent reservoir technologies which get the most out of the abilities of permanent, instrumented wells and remotely activated downhole completions. The strategy, tested with history-matched data from a compartmentalised giant field, proved to reduce operating costs while increasing oil recovery by 27% in this field. (author)

  3. System floorplanning optimization

    KAUST Repository

    Browning, David W.

    2012-12-01

    Notebook and Laptop Original Equipment Manufacturers (OEMs) place great emphasis on creating unique system designs to differentiate themselves in the mobile market. These systems are developed from the \\'outside in\\' with the focus on how the system is perceived by the end-user. As a consequence, very little consideration is given to the interconnections or power of the devices within the system with a mentality of \\'just make it fit\\'. In this paper we discuss the challenges of Notebook system design and the steps by which system floor-planning tools and algorithms can be used to provide an automated method to optimize this process to ensure all required components most optimally fit inside the Notebook system. © 2012 IEEE.

  4. Multistage stochastic optimization

    CERN Document Server

    Pflug, Georg Ch

    2014-01-01

    Multistage stochastic optimization problems appear in many ways in finance, insurance, energy production and trading, logistics and transportation, among other areas. They describe decision situations under uncertainty and with a longer planning horizon. This book contains a comprehensive treatment of today’s state of the art in multistage stochastic optimization.  It covers the mathematical backgrounds of approximation theory as well as numerous practical algorithms and examples for the generation and handling of scenario trees. A special emphasis is put on estimation and bounding of the modeling error using novel distance concepts, on time consistency and the role of model ambiguity in the decision process. An extensive treatment of examples from electricity production, asset liability management and inventory control concludes the book

  5. Optimal fuel inventory strategies

    International Nuclear Information System (INIS)

    Caspary, P.J.; Hollibaugh, J.B.; Licklider, P.L.; Patel, K.P.

    1990-01-01

    In an effort to maintain their competitive edge, most utilities are reevaluating many of their conventional practices and policies in an effort to further minimize customer revenue requirements without sacrificing system reliability. Over the past several years, Illinois Power has been rethinking its traditional fuel inventory strategies, recognizing that coal supplies are competitive and plentiful and that carrying charges on inventory are expensive. To help the Company achieve one of its strategic corporate goals, an optimal fuel inventory study was performed for its five major coal-fired generating stations. The purpose of this paper is to briefly describe Illinois Power's system and past practices concerning coal inventories, highlight the analytical process behind the optimal fuel inventory study, and discuss some of the recent experiences affecting coal deliveries and economic dispatch

  6. System floorplanning optimization

    KAUST Repository

    Browning, David W.

    2013-01-10

    Notebook and Laptop Original Equipment Manufacturers (OEMs) place great emphasis on creating unique system designs to differentiate themselves in the mobile market. These systems are developed from the \\'outside in\\' with the focus on how the system is perceived by the end-user. As a consequence, very little consideration is given to the interconnections or power of the devices within the system with a mentality of \\'just make it fit\\'. In this paper we discuss the challenges of Notebook system design and the steps by which system floor-planning tools and algorithms can be used to provide an automated method to optimize this process to ensure all required components most optimally fit inside the Notebook system.

  7. Optimizing Active Cyber Defense

    OpenAIRE

    Lu, Wenlian; Xu, Shouhuai; Yi, Xinlei

    2016-01-01

    Active cyber defense is one important defensive method for combating cyber attacks. Unlike traditional defensive methods such as firewall-based filtering and anti-malware tools, active cyber defense is based on spreading "white" or "benign" worms to combat against the attackers' malwares (i.e., malicious worms) that also spread over the network. In this paper, we initiate the study of {\\em optimal} active cyber defense in the setting of strategic attackers and/or strategic defenders. Specific...

  8. THE MARKETING MIX OPTIMIZATION

    OpenAIRE

    SABOU FELICIA

    2014-01-01

    The paper presents the marketing mix and the necessity of the marketing mix optimization. In the marketing mix a particularly important issue is to choose the best combination of its variables, this lead to the achievement objectives, in time. Choosing the right marketing mix is possible only by reporting information to some clear benchmarks, these criteria a related to the objective of the company at the time of analyze. The study shows that the companies must give a great importance to opti...

  9. Optimal intermittent search strategies

    International Nuclear Information System (INIS)

    Rojo, F; Budde, C E; Wio, H S

    2009-01-01

    We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion

  10. CRM System Optimization

    OpenAIRE

    Fučík, Ivan

    2015-01-01

    This thesis is focused on CRM solutions in small and medium-sized organizations with respect to the quality of their customer relationship. The main goal of this work is to design an optimal CRM solution in the environment of real organization. To achieve this goal it is necessary to understand the theoretical basis of several topics, such as organizations and their relationship with customers, CRM systems, their features and trends. On the basis of these theoretical topics it is possible to ...

  11. Airfoil design and optimization

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, T. [Stuttgart Univ. (Germany). Inst. fuer Aerodynamik und Gasdynamik

    2001-07-01

    The aerodynamic efficiency of mildly swept wings is mainly influenced by the characteristics of the airfoil sections. The specific design of airfoils is therefore one of the classical tasks of aerodynamics. Since the airfoil characteristics are directly dependent on the inviscid pressure distribution the application of inverse calculation methods is obvious. The direct numerical airfoil optimization offers an alternative to the manual design and attracts increasing interest. (orig.)

  12. Bulbous Bow Shape Optimization

    OpenAIRE

    Blanchard , Louis; Berrini , Elisa; Duvigneau , Régis; Roux , Yann; Mourrain , Bernard; Jean , Eric

    2013-01-01

    International audience; The aim of this study is to prove the usefulness of a bulbous bow for a fishing vessel, in terms of drag reduction, using an automated shape optimization procedure including hydrodynamic simulations. A bulbous bow is an appendage that is known to reduce the drag, thanks to its influence on the bow wave system. However, the definition of the geometrical parameters of the bulb, such as its length and thickness, is not intuitive, as both parameters are coupled with regard...

  13. Topology optimized permanent magnet systems

    Science.gov (United States)

    Bjørk, R.; Bahl, C. R. H.; Insinga, A. R.

    2017-09-01

    Topology optimization of permanent magnet systems consisting of permanent magnets, high permeability iron and air is presented. An implementation of topology optimization for magnetostatics is discussed and three examples are considered. The Halbach cylinder is topology optimized with iron and an increase of 15% in magnetic efficiency is shown. A topology optimized structure to concentrate a homogeneous field is shown to increase the magnitude of the field by 111%. Finally, a permanent magnet with alternating high and low field regions is topology optimized and a Λcool figure of merit of 0.472 is reached, which is an increase of 100% compared to a previous optimized design.

  14. Optimal control for chemical engineers

    CERN Document Server

    Upreti, Simant Ranjan

    2013-01-01

    Optimal Control for Chemical Engineers gives a detailed treatment of optimal control theory that enables readers to formulate and solve optimal control problems. With a strong emphasis on problem solving, the book provides all the necessary mathematical analyses and derivations of important results, including multiplier theorems and Pontryagin's principle.The text begins by introducing various examples of optimal control, such as batch distillation and chemotherapy, and the basic concepts of optimal control, including functionals and differentials. It then analyzes the notion of optimality, de

  15. Security constrained optimal power flow by modern optimization tools

    African Journals Online (AJOL)

    Security constrained optimal power flow by modern optimization tools. ... International Journal of Engineering, Science and Technology ... If you would like more information about how to print, save, and work with PDFs, Highwire Press ...

  16. Lifecycle-Based Swarm Optimization Method for Numerical Optimization

    Directory of Open Access Journals (Sweden)

    Hai Shen

    2014-01-01

    Full Text Available Bioinspired optimization algorithms have been widely used to solve various scientific and engineering problems. Inspired by biological lifecycle, this paper presents a novel optimization algorithm called lifecycle-based swarm optimization (LSO. Biological lifecycle includes four stages: birth, growth, reproduction, and death. With this process, even though individual organism died, the species will not perish. Furthermore, species will have stronger ability of adaptation to the environment and achieve perfect evolution. LSO simulates Biological lifecycle process through six optimization operators: chemotactic, assimilation, transposition, crossover, selection, and mutation. In addition, the spatial distribution of initialization population meets clumped distribution. Experiments were conducted on unconstrained benchmark optimization problems and mechanical design optimization problems. Unconstrained benchmark problems include both unimodal and multimodal cases the demonstration of the optimal performance and stability, and the mechanical design problem was tested for algorithm practicability. The results demonstrate remarkable performance of the LSO algorithm on all chosen benchmark functions when compared to several successful optimization techniques.

  17. Simulation-based optimization parametric optimization techniques and reinforcement learning

    CERN Document Server

    Gosavi, Abhijit

    2003-01-01

    Simulation-Based Optimization: Parametric Optimization Techniques and Reinforcement Learning introduces the evolving area of simulation-based optimization. The book's objective is two-fold: (1) It examines the mathematical governing principles of simulation-based optimization, thereby providing the reader with the ability to model relevant real-life problems using these techniques. (2) It outlines the computational technology underlying these methods. Taken together these two aspects demonstrate that the mathematical and computational methods discussed in this book do work. Broadly speaking, the book has two parts: (1) parametric (static) optimization and (2) control (dynamic) optimization. Some of the book's special features are: *An accessible introduction to reinforcement learning and parametric-optimization techniques. *A step-by-step description of several algorithms of simulation-based optimization. *A clear and simple introduction to the methodology of neural networks. *A gentle introduction to converg...

  18. Security constrained optimal power flow by modern optimization tools

    African Journals Online (AJOL)

    The main objective of an optimal power flow (OPF) functions is to optimize .... It is characterized as propagation of plants and this happens by gametes union. ... ss and different variables, for example, wind, nearby fertilization can have a critic.

  19. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    .... The necessity of anti-optimization approach is first demonstrated, then the anti-optimization techniques are applied to static, dynamic and buckling problems, thus covering the broadest possible set of applications...

  20. THE MARKETING MIX OPTIMIZATION

    Directory of Open Access Journals (Sweden)

    SABOU FELICIA

    2014-02-01

    Full Text Available ing mix a particularly important issue is to choose the best combination of its variables, this lead to the achievement objectives, in time. Choosing the right marketing mix is possible only by reporting information to some clear benchmarks, these criteria a related to the objective of the company at the time of analyze. The study shows that the companies must give a great importance to optimize the marketing mix, because of how its combines and integrates company policies relating to the product, price, distribution and promotion, depends the success or the failure on its market. The practice has shown that if an element of the marketing mix is wrong implemented, marketing strategies and programs do not achieve their objectives, and the company can not generate the expected profit. To optimize the marketing mix, companies should consider the following issues: the resources (materials, financial and human, which will be properly allocated to all the elements of the marketing mix, the specific marketing tools and the relationship of interdependence of all the methods and tools used to optimize the marketing mix.

  1. Subthreshold SPICE Model Optimization

    Science.gov (United States)

    Lum, Gregory; Au, Henry; Neff, Joseph; Bozeman, Eric; Kamin, Nick; Shimabukuro, Randy

    2011-04-01

    The first step in integrated circuit design is the simulation of said design in software to verify proper functionally and design requirements. Properties of the process are provided by fabrication foundries in the form of SPICE models. These SPICE models contain the electrical data and physical properties of the basic circuit elements. A limitation of these models is that the data collected by the foundry only accurately model the saturation region. This is fine for most users, but when operating devices in the subthreshold region they are inadequate for accurate simulation results. This is why optimizing the current SPICE models to characterize the subthreshold region is so important. In order to accurately simulate this region of operation, MOSFETs of varying widths and lengths are fabricated and the electrical test data is collected. From the data collected the parameters of the model files are optimized through parameter extraction rather than curve fitting. With the completed optimized models the circuit designer is able to simulate circuit designs for the sub threshold region accurately.

  2. Optimal shutdown management

    International Nuclear Information System (INIS)

    Bottasso, C L; Croce, A; Riboldi, C E D

    2014-01-01

    The paper presents a novel approach for the synthesis of the open-loop pitch profile during emergency shutdowns. The problem is of interest in the design of wind turbines, as such maneuvers often generate design driving loads on some of the machine components. The pitch profile synthesis is formulated as a constrained optimal control problem, solved numerically using a direct single shooting approach. A cost function expressing a compromise between load reduction and rotor overspeed is minimized with respect to the unknown blade pitch profile. Constraints may include a load reduction not-to-exceed the next dominating loads, a not-to-be-exceeded maximum rotor speed, and a maximum achievable blade pitch rate. Cost function and constraints are computed over a possibly large number of operating conditions, defined so as to cover as well as possible the operating situations encountered in the lifetime of the machine. All such conditions are simulated by using a high-fidelity aeroservoelastic model of the wind turbine, ensuring the accuracy of the evaluation of all relevant parameters. The paper demonstrates the capabilities of the novel proposed formulation, by optimizing the pitch profile of a multi-MW wind turbine. Results show that the procedure can reliably identify optimal pitch profiles that reduce design-driving loads, in a fully automated way

  3. Optimal shutdown management

    Science.gov (United States)

    Bottasso, C. L.; Croce, A.; Riboldi, C. E. D.

    2014-06-01

    The paper presents a novel approach for the synthesis of the open-loop pitch profile during emergency shutdowns. The problem is of interest in the design of wind turbines, as such maneuvers often generate design driving loads on some of the machine components. The pitch profile synthesis is formulated as a constrained optimal control problem, solved numerically using a direct single shooting approach. A cost function expressing a compromise between load reduction and rotor overspeed is minimized with respect to the unknown blade pitch profile. Constraints may include a load reduction not-to-exceed the next dominating loads, a not-to-be-exceeded maximum rotor speed, and a maximum achievable blade pitch rate. Cost function and constraints are computed over a possibly large number of operating conditions, defined so as to cover as well as possible the operating situations encountered in the lifetime of the machine. All such conditions are simulated by using a high-fidelity aeroservoelastic model of the wind turbine, ensuring the accuracy of the evaluation of all relevant parameters. The paper demonstrates the capabilities of the novel proposed formulation, by optimizing the pitch profile of a multi-MW wind turbine. Results show that the procedure can reliably identify optimal pitch profiles that reduce design-driving loads, in a fully automated way.

  4. Optimization in radiological protection

    International Nuclear Information System (INIS)

    Acosta Perez, Clarice de Freitas

    1996-01-01

    The optimization concept in radiation protection is, in its essence, practical. In each aspect that we deal with the man, it is necessary to take frequent decisions such as: what is the protection level to be pursued, since the protection levels under consideration provide doses lower than the appropriate annual limits. The optimization gives a basic framework of the minding that is appropriate to conduct to a balance kind of the resources available for the protection and protection level obtained against a multitude of factors and constrains in a manner to obtain the best result. In this work, was performed the optimization, from the radiation protection point of view, of a facility project who enclose two shielded hot cells where will be handled UO 2 small plate with 50% of U-235 burn-up, irradiated in the research swimming pool reactor, IEA-R1. To obtain this goal were specified the relevant factors and criteria, were applied the main techniques used in a decision-making in radiological protection, presently adopted and was performed a sensibility study of the factors and criteria used in this work. In order to obtain a greater agility in applying the techniques for decision-making was developed a micro computer program. (author)

  5. PWR fuel management optimization

    International Nuclear Information System (INIS)

    Dumas, Michel.

    1981-10-01

    This report is aimed to the optimization of the refueling pattern of a nuclear reactor. At the beginning of a reactor cycle a batch of fuel assemblies is available: the physical properties of the assemblies are known: the mathematical problem is to determine the refueling pattern which maximizes the reactivity or which provides the flattest possible power distribution. The state of the core is mathematically characterized by a system of partial derivative equations, its smallest eigenvalue and the associated eigenvector. After a study of the convexity properties of the problem, two algorithms are proposed. The first one exhanges assemblies to improve the starting configurations. The enumeration of the exchanges is limited to the 2 by 2, 3 by 3, 4 by 4 permutations. The second one builds a solution in two steps: in the first step the discrete variables are replaced by continuous variables. The non linear optimization problem obtained is solved by ''the Method of Approximation Programming'' and in the second step, the refuelling pattern which provides the best approximation of the optimal power distribution is searched by a Branch an d Bound Method [fr

  6. Optimally segmented magnetic structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bahl, Christian; Bjørk, Rasmus

    We present a semi-analytical algorithm for magnet design problems, which calculates the optimal way to subdivide a given design region into uniformly magnetized segments.The availability of powerful rare-earth magnetic materials such as Nd-Fe-B has broadened the range of applications of permanent...... is not available.We will illustrate the results for magnet design problems from different areas, such as electric motors/generators (as the example in the picture), beam focusing for particle accelerators and magnetic refrigeration devices.......We present a semi-analytical algorithm for magnet design problems, which calculates the optimal way to subdivide a given design region into uniformly magnetized segments.The availability of powerful rare-earth magnetic materials such as Nd-Fe-B has broadened the range of applications of permanent...... magnets[1][2]. However, the powerful rare-earth magnets are generally expensive, so both the scientific and industrial communities have devoted a lot of effort into developing suitable design methods. Even so, many magnet optimization algorithms either are based on heuristic approaches[3...

  7. Infrared Drying Parameter Optimization

    Science.gov (United States)

    Jackson, Matthew R.

    In recent years, much research has been done to explore direct printing methods, such as screen and inkjet printing, as alternatives to the traditional lithographic process. The primary motivation is reduction of the material costs associated with producing common electronic devices. Much of this research has focused on developing inkjet or screen paste formulations that can be printed on a variety of substrates, and which have similar conductivity performance to the materials currently used in the manufacturing of circuit boards and other electronic devices. Very little research has been done to develop a process that would use direct printing methods to manufacture electronic devices in high volumes. This study focuses on developing and optimizing a drying process for conductive copper ink in a high volume manufacturing setting. Using an infrared (IR) dryer, it was determined that conductive copper prints could be dried in seconds or minutes as opposed to tens of minutes or hours that it would take with other drying devices, such as a vacuum oven. In addition, this study also identifies significant parameters that can affect the conductivity of IR dried prints. Using designed experiments and statistical analysis; the dryer parameters were optimized to produce the best conductivity performance for a specific ink formulation and substrate combination. It was determined that for an ethylene glycol, butanol, 1-methoxy 2- propanol ink formulation printed on Kapton, the optimal drying parameters consisted of a dryer height of 4 inches, a temperature setting between 190 - 200°C, and a dry time of 50-65 seconds depending on the printed film thickness as determined by the number of print passes. It is important to note that these parameters are optimized specifically for the ink formulation and substrate used in this study. There is still much research that needs to be done into optimizing the IR dryer for different ink substrate combinations, as well as developing a

  8. Ames Optimized TCA Configuration

    Science.gov (United States)

    Cliff, Susan E.; Reuther, James J.; Hicks, Raymond M.

    1999-01-01

    Configuration design at Ames was carried out with the SYN87-SB (single block) Euler code using a 193 x 49 x 65 C-H grid. The Euler solver is coupled to the constrained (NPSOL) and the unconstrained (QNMDIF) optimization packages. Since the single block grid is able to model only wing-body configurations, the nacelle/diverter effects were included in the optimization process by SYN87's option to superimpose the nacelle/diverter interference pressures on the wing. These interference pressures were calculated using the AIRPLANE code. AIRPLANE is an Euler solver that uses a unstructured tetrahedral mesh and is capable of computations about arbitrary complete configurations. In addition, the buoyancy effects of the nacelle/diverters were also included in the design process by imposing the pressure field obtained during the design process onto the triangulated surfaces of the nacelle/diverter mesh generated by AIRPLANE. The interference pressures and nacelle buoyancy effects are added to the final forces after each flow field calculation. Full details of the (recently enhanced) ghost nacelle capability are given in a related talk. The pseudo nacelle corrections were greatly improved during this design cycle. During the Ref H and Cycle 1 design activities, the nacelles were only translated and pitched. In the cycle 2 design effort the nacelles can translate vertically, and pitch to accommodate the changes in the lower surface geometry. The diverter heights (between their leading and trailing edges) were modified during design as the shape of the lower wing changed, with the drag of the diverter changing accordingly. Both adjoint and finite difference gradients were used during optimization. The adjoint-based gradients were found to give good direction in the design space for configurations near the starting point, but as the design approached a minimum, the finite difference gradients were found to be more accurate. Use of finite difference gradients was limited by the

  9. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome

    DEFF Research Database (Denmark)

    White, Janson; Mazzeu, Juliana F; Hoischen, Alexander

    2015-01-01

    Robinow syndrome is a genetically heterogeneous disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features and for which both autosomal-recessive and autosomal-dominant inheritance patterns have been described. Causative variants in the non-canonical ...

  10. Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons

    Czech Academy of Sciences Publication Activity Database

    Čajánek, L.; Ganji, R.S.; Henriques-Oliveira, C.; Theofilopoulos, S.; Koník, P.; Bryja, Vítězslav; Arenas, E.

    2013-01-01

    Roč. 33, č. 1 (2013), s. 59-70 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Grant - others:GA ČR(CZ) GA204/09/0498 Institutional support: RVO:68081707 Keywords : RHO-GTPASES * CELL POLARITY * DISHEVELLED PHOSPHORYLATION Subject RIV: BO - Biophysics Impact factor: 5.036, year: 2013

  11. Topology optimized electrothermal polysilicon microgrippers

    DEFF Research Database (Denmark)

    Sardan Sukas, Özlem; Petersen, Dirch Hjorth; Mølhave, Kristian

    2008-01-01

    This paper presents the topology optimized design procedure and fabrication of electrothermal polysilicon microgrippers for nanomanipulation purposes. Performance of the optimized microactuators is compared with a conventional three-beam microactuator design through finite element analysis...

  12. Metaheuristic optimization in power engineering

    CERN Document Server

    Radosavljević, Jordan

    2018-01-01

    This book describes the principles of solving various problems in power engineering via the application of selected metaheuristic optimization methods including genetic algorithms, particle swarm optimization, and the gravitational search algorithm.

  13. Taking Stock of Unrealistic Optimism

    Science.gov (United States)

    Shepperd, James A.; Klein, William M. P.; Waters, Erika A.; Weinstein, Neil D.

    2015-01-01

    Researchers have used terms such as unrealistic optimism and optimistic bias to refer to concepts that are similar but not synonymous. Drawing from three decades of research, we critically discuss how researchers define unrealistic optimism and we identify four types that reflect different measurement approaches: unrealistic absolute optimism at the individual and group level and unrealistic comparative optimism at the individual and group level. In addition, we discuss methodological criticisms leveled against research on unrealistic optimism and note that the criticisms are primarily relevant to only one type—the group form of unrealistic comparative optimism. We further clarify how the criticisms are not nearly as problematic even for unrealistic comparative optimism as they might seem. Finally, we note boundary conditions on the different types of unrealistic optimism and reflect on five broad questions that deserve further attention. PMID:26045714

  14. Taking Stock of Unrealistic Optimism.

    Science.gov (United States)

    Shepperd, James A; Klein, William M P; Waters, Erika A; Weinstein, Neil D

    2013-07-01

    Researchers have used terms such as unrealistic optimism and optimistic bias to refer to concepts that are similar but not synonymous. Drawing from three decades of research, we critically discuss how researchers define unrealistic optimism and we identify four types that reflect different measurement approaches: unrealistic absolute optimism at the individual and group level and unrealistic comparative optimism at the individual and group level. In addition, we discuss methodological criticisms leveled against research on unrealistic optimism and note that the criticisms are primarily relevant to only one type-the group form of unrealistic comparative optimism. We further clarify how the criticisms are not nearly as problematic even for unrealistic comparative optimism as they might seem. Finally, we note boundary conditions on the different types of unrealistic optimism and reflect on five broad questions that deserve further attention.

  15. Combinatorial optimization in foundry practice

    Science.gov (United States)

    Antamoshkin, A. N.; Masich, I. S.

    2016-04-01

    The multicriteria mathematical model of foundry production capacity planning is suggested in the paper. The model is produced in terms of pseudo-Boolean optimization theory. Different search optimization methods were used to solve the obtained problem.

  16. Time-Space Topology Optimization

    DEFF Research Database (Denmark)

    Jensen, Jakob Søndergaard

    2008-01-01

    A method for space-time topology optimization is outlined. The space-time optimization strategy produces structures with optimized material distributions that vary in space and in time. The method is demonstrated for one-dimensional wave propagation in an elastic bar that has a time-dependent Young......’s modulus and is subjected to a transient load. In the example an optimized dynamic structure is demonstrated that compresses a propagating Gauss pulse....

  17. Coil Optimization for HTS Machines

    DEFF Research Database (Denmark)

    Mijatovic, Nenad; Jensen, Bogi Bech; Abrahamsen, Asger Bech

    An optimization approach of HTS coils in HTS synchronous machines (SM) is presented. The optimization is aimed at high power SM suitable for direct driven wind turbines applications. The optimization process was applied to a general radial flux machine with a peak air gap flux density of ~3T...... is suitable for which coil segment is presented. Thus, the performed study gives valuable input for the coil design of HTS machines ensuring optimal usage of HTS tapes....

  18. Stochastic optimization: beyond mathematical programming

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Stochastic optimization, among which bio-inspired algorithms, is gaining momentum in areas where more classical optimization algorithms fail to deliver satisfactory results, or simply cannot be directly applied. This presentation will introduce baseline stochastic optimization algorithms, and illustrate their efficiency in different domains, from continuous non-convex problems to combinatorial optimization problem, to problems for which a non-parametric formulation can help exploring unforeseen possible solution spaces.

  19. Introduction to optimal control theory

    International Nuclear Information System (INIS)

    Agrachev, A.A.

    2002-01-01

    These are lecture notes of the introductory course in Optimal Control theory treated from the geometric point of view. Optimal Control Problem is reduced to the study of controls (and corresponding trajectories) leading to the boundary of attainable sets. We discuss Pontryagin Maximum Principle, basic existence results, and apply these tools to concrete simple optimal control problems. Special sections are devoted to the general theory of linear time-optimal problems and linear-quadratic problems. (author)

  20. SOCIAL NETWORK OPTIMIZATION A NEW METHAHEURISTIC FOR GENERAL OPTIMIZATION PROBLEMS

    Directory of Open Access Journals (Sweden)

    Hassan Sherafat

    2017-12-01

    Full Text Available In the recent years metaheuristics were studied and developed as powerful technics for hard optimization problems. Some of well-known technics in this field are: Genetic Algorithms, Tabu Search, Simulated Annealing, Ant Colony Optimization, and Swarm Intelligence, which are applied successfully to many complex optimization problems. In this paper, we introduce a new metaheuristic for solving such problems based on social networks concept, named as Social Network Optimization – SNO. We show that a wide range of np-hard optimization problems may be solved by SNO.

  1. Solving Optimization Problems via Vortex Optimization Algorithm and Cognitive Development Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Ahmet Demir

    2017-01-01

    Full Text Available In the fields which require finding the most appropriate value, optimization became a vital approach to employ effective solutions. With the use of optimization techniques, many different fields in the modern life have found solutions to their real-world based problems. In this context, classical optimization techniques have had an important popularity. But after a while, more advanced optimization problems required the use of more effective techniques. At this point, Computer Science took an important role on providing software related techniques to improve the associated literature. Today, intelligent optimization techniques based on Artificial Intelligence are widely used for optimization problems. The objective of this paper is to provide a comparative study on the employment of classical optimization solutions and Artificial Intelligence solutions for enabling readers to have idea about the potential of intelligent optimization techniques. At this point, two recently developed intelligent optimization algorithms, Vortex Optimization Algorithm (VOA and Cognitive Development Optimization Algorithm (CoDOA, have been used to solve some multidisciplinary optimization problems provided in the source book Thomas' Calculus 11th Edition and the obtained results have compared with classical optimization solutions. 

  2. Risk Based Optimal Fatigue Testing

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Faber, M.H.; Kroon, I.B.

    1992-01-01

    Optimal fatigue life testing of materials is considered. Based on minimization of the total expected costs of a mechanical component a strategy is suggested to determine the optimal stress range levels for which additional experiments are to be performed together with an optimal value...

  3. Partisan optimism and political bargaining

    DEFF Research Database (Denmark)

    Jensen, Thomas; Madum, Andreas

    2017-01-01

    to explore the implications of partisan optimism for political bargaining. We show that increased optimism among a partisan group leads to a stronger bargaining position for their party, but may hurt its electoral prospects. Another main finding is that even high levels of partisan optimism do...

  4. Optimism and Well-Being

    Science.gov (United States)

    Reivich, Karen

    2010-01-01

    Dictionary definitions of optimism encompass two related concepts. The first of these is a hopeful disposition or a conviction that good will ultimately prevail. The second, broader conception of optimism refers to the belief, or the inclination to believe, that the world is the best of all possible worlds. In psychological research, optimism has…

  5. Thermodynamic optimization of power plants

    NARCIS (Netherlands)

    Haseli, Y.

    2011-01-01

    Thermodynamic Optimization of Power Plants aims to establish and illustrate comparative multi-criteria optimization of various models and configurations of power plants. It intends to show what optimization objectives one may define on the basis of the thermodynamic laws, and how they can be applied

  6. Multicriteria VMAT optimization

    International Nuclear Information System (INIS)

    Craft, David; McQuaid, Dualta; Wala, Jeremiah; Chen, Wei; Salari, Ehsan; Bortfeld, Thomas

    2012-01-01

    Purpose: To make the planning of volumetric modulated arc therapy (VMAT) faster and to explore the tradeoffs between planning objectives and delivery efficiency. Methods: A convex multicriteria dose optimization problem is solved for an angular grid of 180 equi-spaced beams. This allows the planner to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus organ at risk sparing. The selected plan is then made VMAT deliverable by a fluence map merging and sequencing algorithm, which combines neighboring fluence maps based on a similarity score and then delivers the merged maps together, simplifying delivery. Successive merges are made as long as the dose distribution quality is maintained. The complete algorithm is called VMERGE. Results: VMERGE is applied to three cases: a prostate, a pancreas, and a brain. In each case, the selected Pareto-optimal plan is matched almost exactly with the VMAT merging routine, resulting in a high quality plan delivered with a single arc in less than 5 min on average. Conclusions: VMERGE offers significant improvements over existing VMAT algorithms. The first is the multicriteria planning aspect, which greatly speeds up planning time and allows the user to select the plan, which represents the most desirable compromise between target coverage and organ at risk sparing. The second is the user-chosen epsilon-optimality guarantee of the final VMAT plan. Finally, the user can explore the tradeoff between delivery time and plan quality, which is a fundamental aspect of VMAT that cannot be easily investigated with current commercial planning systems.

  7. Optimization of Mangala Hydropower Station, Pakistan, using Optimization Techniques

    Directory of Open Access Journals (Sweden)

    Zaman Muhammad

    2017-01-01

    Full Text Available Hydropower generation is one of the key element in the economy of a country. The present study focusses on the optimal electricity generation from the Mangla reservoir in Pakistan. A mathematical model has been developed for the Mangla hydropower station and particle swarm and genetic algorithm optimization techniques were applied at this model for optimal electricity generation. Results revealed that electricity production increases with the application of optimization techniques at the proposed mathematical model. Genetic Algorithm can produce maximum electricity than Particle swarm optimization but the time of execution of particle swarm optimization is much lesser than the Genetic algorithm. Mangla hydropower station can produce up to 59*109 kWh electricity by using the flows optimally than 47*108 kWh production from traditional methods.

  8. Example of feedstock optimization

    International Nuclear Information System (INIS)

    Boustros, E.

    1991-01-01

    An example of feedstock optimization at an olefins plant which has the flexibility to process different kinds of raw materials while maintaining the same product slate, is presented. Product demand and prices, and the number of units in service as well as the required resources to operate these units are considered to be fixed. The plant profitability is a function of feedstock choice, plus constant costs which are the non-volume related costs. The objective is to find a set or combination of feedstocks that could match the client product demands and fall within the unit's design and capacity, while maximizing the financial operating results

  9. Duality in vector optimization

    CERN Document Server

    Bot, Radu Ioan

    2009-01-01

    This book presents fundamentals and comprehensive results regarding duality for scalar, vector and set-valued optimization problems in a general setting. After a preliminary chapter dedicated to convex analysis and minimality notions of sets with respect to partial orderings induced by convex cones a chapter on scalar conjugate duality follows. Then investigations on vector duality based on scalar conjugacy are made. Weak, strong and converse duality statements are delivered and connections to classical results from the literature are emphasized. One chapter is exclusively consecrated to the s

  10. Optimizing production under uncertainty

    DEFF Research Database (Denmark)

    Rasmussen, Svend

    This Working Paper derives criteria for optimal production under uncertainty based on the state-contingent approach (Chambers and Quiggin, 2000), and discusses po-tential problems involved in applying the state-contingent approach in a normative context. The analytical approach uses the concept...... of state-contingent production functions and a definition of inputs including both sort of input, activity and alloca-tion technology. It also analyses production decisions where production is combined with trading in state-contingent claims such as insurance contracts. The final part discusses...

  11. Optimization Foundations and Applications

    CERN Document Server

    Miller, H Ronald

    2011-01-01

    A thorough and highly accessible resource for analysts in a broad range of social sciences. Optimization: Foundations and Applications presents a series of approaches to the challenges faced by analysts who must find the best way to accomplish particular objectives, usually with the added complication of constraints on the available choices. Award-winning educator Ronald E. Miller provides detailed coverage of both classical, calculus-based approaches and newer, computer-based iterative methods. Dr. Miller lays a solid foundation for both linear and nonlinear models and quickly moves on to dis

  12. Optimal intermittent search strategies

    Energy Technology Data Exchange (ETDEWEB)

    Rojo, F; Budde, C E [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, X5000HUA Cordoba (Argentina); Wio, H S [Instituto de Fisica de Cantabria, Universidad de Cantabria and CSIC E-39005 Santander (Spain)

    2009-03-27

    We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion.

  13. Search Engine Optimization

    CERN Document Server

    Davis, Harold

    2006-01-01

    SEO--short for Search Engine Optimization--is the art, craft, and science of driving web traffic to web sites. Web traffic is food, drink, and oxygen--in short, life itself--to any web-based business. Whether your web site depends on broad, general traffic, or high-quality, targeted traffic, this PDF has the tools and information you need to draw more traffic to your site. You'll learn how to effectively use PageRank (and Google itself); how to get listed, get links, and get syndicated; and much more. The field of SEO is expanding into all the possible ways of promoting web traffic. This

  14. Finding optimal exact reducts

    KAUST Repository

    AbouEisha, Hassan M.

    2014-01-01

    The problem of attribute reduction is an important problem related to feature selection and knowledge discovery. The problem of finding reducts with minimum cardinality is NP-hard. This paper suggests a new algorithm for finding exact reducts with minimum cardinality. This algorithm transforms the initial table to a decision table of a special kind, apply a set of simplification steps to this table, and use a dynamic programming algorithm to finish the construction of an optimal reduct. I present results of computer experiments for a collection of decision tables from UCIML Repository. For many of the experimented tables, the simplification steps solved the problem.

  15. Office lighting systems: Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Dagnino, U. (ENEL, Milan (Italy))

    1990-09-01

    Relative to office lighting systems, in particular, those making use of tubular fluorescent lamps, currently available on the international market, this paper tries to develop lighting system, design optimization criteria. The comparative assessment of the various design possibilities considers operating cost, energy consumption, and occupational comfort/safety aspects such as lighting level uniformity and equilibrium, reduction of glare and reflection, natural/artificial lighting balance, programmed switching, computerized control systems for multi-use requirements in large areas, programmed maintenance for greater efficiency and reliability.

  16. Optimization of partial search

    International Nuclear Information System (INIS)

    Korepin, Vladimir E

    2005-01-01

    A quantum Grover search algorithm can find a target item in a database faster than any classical algorithm. One can trade accuracy for speed and find a part of the database (a block) containing the target item even faster; this is partial search. A partial search algorithm was recently suggested by Grover and Radhakrishnan. Here we optimize it. Efficiency of the search algorithm is measured by the number of queries to the oracle. The author suggests a new version of the Grover-Radhakrishnan algorithm which uses a minimal number of such queries. The algorithm can run on the same hardware that is used for the usual Grover algorithm. (letter to the editor)

  17. BRAIN Journal - Solving Optimization Problems via Vortex Optimization Algorithm and Cognitive Development Optimization Algorithm

    OpenAIRE

    Ahmet Demir; Utku Kose

    2016-01-01

    ABSTRACT In the fields which require finding the most appropriate value, optimization became a vital approach to employ effective solutions. With the use of optimization techniques, many different fields in the modern life have found solutions to their real-world based problems. In this context, classical optimization techniques have had an important popularity. But after a while, more advanced optimization problems required the use of more effective techniques. At this point, Computer Sc...

  18. Solving Optimization Problems via Vortex Optimization Algorithm and Cognitive Development Optimization Algorithm

    OpenAIRE

    Ahmet Demir; Utku kose

    2017-01-01

    In the fields which require finding the most appropriate value, optimization became a vital approach to employ effective solutions. With the use of optimization techniques, many different fields in the modern life have found solutions to their real-world based problems. In this context, classical optimization techniques have had an important popularity. But after a while, more advanced optimization problems required the use of more effective techniques. At this point, Computer Science took an...

  19. Optimizing accelerator technology

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    A new EU-funded research and training network, oPAC, is bringing together 22 universities, research centres and industry partners to optimize particle accelerator technology. CERN is one of the network’s main partners and will host 5 early-stage researchers in the BE department.   A diamond detector that will be used for novel beam diagnostics applications in the oPAC project based at CIVIDEC. (Image courtesy of CIVIDEC.) As one of the largest Marie Curie Initial Training Networks ever funded by the EU – to the tune of €6 million – oPAC extends well beyond the particle physics community. “Accelerator physics has become integral to research in almost every scientific discipline – be it biology and life science, medicine, geology and material science, or fundamental physics,” explains Carsten P. Welsch, oPAC co-ordinator based at the University of Liverpool. “By optimizing the operation of accelerators, all of these...

  20. E85 Optimized Engine

    Energy Technology Data Exchange (ETDEWEB)

    Bower, Stanley [Ford Motor Company, Dearborn, MI (United States)

    2011-12-31

    A 5.0L V8 twin-turbocharged direct injection engine was designed, built, and tested for the purpose of assessing the fuel economy and performance in the F-Series pickup of the Dual Fuel engine concept and of an E85 optimized FFV engine. Additionally, production 3.5L gasoline turbocharged direct injection (GTDI) EcoBoost engines were converted to Dual Fuel capability and used to evaluate the cold start emissions and fuel system robustness of the Dual Fuel engine concept. Project objectives were: to develop a roadmap to demonstrate a minimized fuel economy penalty for an F-Series FFV truck with a highly boosted, high compression ratio spark ignition engine optimized to run with ethanol fuel blends up to E85; to reduce FTP 75 energy consumption by 15% - 20% compared to an equally powered vehicle with a current production gasoline engine; and to meet ULEV emissions, with a stretch target of ULEV II / Tier II Bin 4. All project objectives were met or exceeded.

  1. Synthesizing optimal waste blends

    International Nuclear Information System (INIS)

    Narayan, V.; Diwekar, W.M.; Hoza, M.

    1996-01-01

    Vitrification of tank wastes to form glass is a technique that will be used for the disposal of high-level waste at Hanford. Process and storage economics show that minimizing the total number of glass logs produced is the key to keeping cost as low as possible. The amount of glass produced can be reduced by blending of the wastes. The optimal way to combine the tanks to minimize the vole of glass can be determined from a discrete blend calculation. However, this problem results in a combinatorial explosion as the number of tanks increases. Moreover, the property constraints make this problem highly nonconvex where many algorithms get trapped in local minima. In this paper the authors examine the use of different combinatorial optimization approaches to solve this problem. A two-stage approach using a combination of simulated annealing and nonlinear programming (NLP) is developed. The results of different methods such as the heuristics approach based on human knowledge and judgment, the mixed integer nonlinear programming (MINLP) approach with GAMS, and branch and bound with lower bound derived from the structure of the given blending problem are compared with this coupled simulated annealing and NLP approach

  2. Giga-Voxel Structural Optimization

    DEFF Research Database (Denmark)

    Aage, Niels; Andreassen, Erik; Lazarov, Boyan Stefanov

    2017-01-01

    The optimal topology of large structural systems has until now been concerned with the design of individual parts and not that of complete assemblies. However, due to recent advances in numerical algorithms tailored for large scale structural optimization this limitation can now be circumvented....... In this work we present several examplesdisplaying how high resolution topology optimization can be used to obtain new, as well as already known, insight within the field of structural optimization. To demonstrate the capabilities of the developed framework we apply it to the design of the supporting structure...... topology optimization provides new insight and possible weight savings forfuture aircraft designs....

  3. Topology optimized permanent magnet systems

    DEFF Research Database (Denmark)

    Bjørk, Rasmus; Bahl, Christian; Insinga, Andrea Roberto

    2017-01-01

    Topology optimization of permanent magnet systems consisting of permanent magnets, high permeability iron and air is presented. An implementation of topology optimization for magnetostatics is discussed and three examples are considered. The Halbach cylinder is topology optimized with iron...... and an increase of 15% in magnetic efficiency is shown. A topology optimized structure to concentrate a homogeneous field is shown to increase the magnitude of the field by 111%. Finally, a permanent magnet with alternating high and low field regions is topology optimized and a ΛcoolΛcool figure of merit of 0...

  4. The Theory of Optimal Taxation

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    The paper discusses the implications of optimal tax theory for the debates on uniform commodity taxation and neutral capital income taxation. While strong administrative and political economy arguments in favor of uniform and neutral taxation remain, recent advances in optimal tax theory suggest...... that the information needed to implement the differentiated taxation prescribed by optimal tax theory may be easier to obtain than previously believed. The paper also points to the strong similarity between optimal commodity tax rules and the rules for optimal source-based capital income taxation...

  5. The theory of optimal taxation

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    2007-01-01

    The paper discusses the implications of optimal tax theory for the debates on uniform commodity taxation and neutral capital income taxation. While strong administrative and political economy arguments in favor of uniform and neutral taxation remain, recent advances in optimal tax theory suggest...... that the information needed to implement the differentiated taxation prescribed by optimal tax theory may be easier to obtain than previously believed. The paper also points to the strong similarity between optimal commodity tax rules and the rules for optimal source-based capital income taxation...

  6. Optimal Control of Mechanical Systems

    Directory of Open Access Journals (Sweden)

    Vadim Azhmyakov

    2007-01-01

    Full Text Available In the present work, we consider a class of nonlinear optimal control problems, which can be called “optimal control problems in mechanics.” We deal with control systems whose dynamics can be described by a system of Euler-Lagrange or Hamilton equations. Using the variational structure of the solution of the corresponding boundary-value problems, we reduce the initial optimal control problem to an auxiliary problem of multiobjective programming. This technique makes it possible to apply some consistent numerical approximations of a multiobjective optimization problem to the initial optimal control problem. For solving the auxiliary problem, we propose an implementable numerical algorithm.

  7. Optimal taxation with household production

    DEFF Research Database (Denmark)

    Kleven, Henrik Jacobsen; Richter, Wolfram F.; Sørensen, Peter Birch

    2000-01-01

    on consumer services even if such services are complements to leisure. Second, we find that when services and other goods are equally substitutable for leisure, so that uniform commodity taxation would be optimal in the absence of home production, the optimal tax structure will certainly involve a relatively......This paper suggests that the optimal tax system should favour market-produced services which are close substitutes for home-produced services. First, we modify the classical Corlett-Hague rule for optimal commodity taxation by showing that it may be optimal to impose a relatively low tax rate...... low tax rate on consumer services...

  8. Application of Nontraditional Optimization Techniques for Airfoil Shape Optimization

    Directory of Open Access Journals (Sweden)

    R. Mukesh

    2012-01-01

    Full Text Available The method of optimization algorithms is one of the most important parameters which will strongly influence the fidelity of the solution during an aerodynamic shape optimization problem. Nowadays, various optimization methods, such as genetic algorithm (GA, simulated annealing (SA, and particle swarm optimization (PSO, are more widely employed to solve the aerodynamic shape optimization problems. In addition to the optimization method, the geometry parameterization becomes an important factor to be considered during the aerodynamic shape optimization process. The objective of this work is to introduce the knowledge of describing general airfoil geometry using twelve parameters by representing its shape as a polynomial function and coupling this approach with flow solution and optimization algorithms. An aerodynamic shape optimization problem is formulated for NACA 0012 airfoil and solved using the methods of simulated annealing and genetic algorithm for 5.0 deg angle of attack. The results show that the simulated annealing optimization scheme is more effective in finding the optimum solution among the various possible solutions. It is also found that the SA shows more exploitation characteristics as compared to the GA which is considered to be more effective explorer.

  9. Optimal Ski Jump

    Science.gov (United States)

    Rebilas, Krzysztof

    2013-02-01

    Consider a skier who goes down a takeoff ramp, attains a speed V, and jumps, attempting to land as far as possible down the hill below (Fig. 1). At the moment of takeoff the angle between the skier's velocity and the horizontal is α. What is the optimal angle α that makes the jump the longest possible for the fixed magnitude of the velocity V? Of course, in practice, this is a very sophisticated problem; the skier's range depends on a variety of complex factors in addition to V and α. However, if we ignore these and assume the jumper is in free fall between the takeoff ramp and the landing point below, the problem becomes an exercise in kinematics that is suitable for introductory-level students. The solution is presented here.

  10. Optimized nanoporous materials.

    Energy Technology Data Exchange (ETDEWEB)

    Braun, Paul V. (University of Illinois at Urbana-Champaign, Urbana, IL); Langham, Mary Elizabeth; Jacobs, Benjamin W.; Ong, Markus D.; Narayan, Roger J. (North Carolina State University, Raleigh, NC); Pierson, Bonnie E. (North Carolina State University, Raleigh, NC); Gittard, Shaun D. (North Carolina State University, Raleigh, NC); Robinson, David B.; Ham, Sung-Kyoung (Korea Basic Science Institute, Gangneung, South Korea); Chae, Weon-Sik (Korea Basic Science Institute, Gangneung, South Korea); Gough, Dara V. (University of Illinois at Urbana-Champaign, Urbana, IL); Wu, Chung-An Max; Ha, Cindy M.; Tran, Kim L.

    2009-09-01

    Nanoporous materials have maximum practical surface areas for electrical charge storage; every point in an electrode is within a few atoms of an interface at which charge can be stored. Metal-electrolyte interfaces make best use of surface area in porous materials. However, ion transport through long, narrow pores is slow. We seek to understand and optimize the tradeoff between capacity and transport. Modeling and measurements of nanoporous gold electrodes has allowed us to determine design principles, including the fact that these materials can deplete salt from the electrolyte, increasing resistance. We have developed fabrication techniques to demonstrate architectures inspired by these principles that may overcome identified obstacles. A key concept is that electrodes should be as close together as possible; this is likely to involve an interpenetrating pore structure. However, this may prove extremely challenging to fabricate at the finest scales; a hierarchically porous structure can be a worthy compromise.

  11. On optimal population paths

    CERN Document Server

    Lane, John S

    1977-01-01

    The overall purpose of this monograph is to integrate and critically evaluate the existing literature in the area of optimal joint savings population programs. The existing diverse presentations are all seen to be discussions within a unified framework. The central problem is to compare the desirability of alternative inter-temporal sequences of total savings and population sizes. Of critical importance is whether one regards persons as the fundamental moral entities or whether one takes Sidgwick's viewpoint that something good being the result of one's action is the baSic reason for dOing anything. The latter viewpoint is consistent with defining a complete social preference ordering over these alternative sequences. Since part of one's interest is to evaluate the consequences of various ethical beliefs a com­ parative study of several such orderings is presented; in particular the Mill-Wolfe average utilitarian, and Sidgwick-Meade classical utilitarian) formulations. A possible problem with the social pref...

  12. LHCb trigger streams optimization

    Science.gov (United States)

    Derkach, D.; Kazeev, N.; Neychev, R.; Panin, A.; Trofimov, I.; Ustyuzhanin, A.; Vesterinen, M.

    2017-10-01

    The LHCb experiment stores around 1011 collision events per year. A typical physics analysis deals with a final sample of up to 107 events. Event preselection algorithms (lines) are used for data reduction. Since the data are stored in a format that requires sequential access, the lines are grouped into several output file streams, in order to increase the efficiency of user analysis jobs that read these data. The scheme efficiency heavily depends on the stream composition. By putting similar lines together and balancing the stream sizes it is possible to reduce the overhead. We present a method for finding an optimal stream composition. The method is applied to a part of the LHCb data (Turbo stream) on the stage where it is prepared for user physics analysis. This results in an expected improvement of 15% in the speed of user analysis jobs, and will be applied on data to be recorded in 2017.

  13. Database Optimizing Services

    Directory of Open Access Journals (Sweden)

    Adrian GHENCEA

    2010-12-01

    Full Text Available Almost every organization has at its centre a database. The database provides support for conducting different activities, whether it is production, sales and marketing or internal operations. Every day, a database is accessed for help in strategic decisions. The satisfaction therefore of such needs is entailed with a high quality security and availability. Those needs can be realised using a DBMS (Database Management System which is, in fact, software for a database. Technically speaking, it is software which uses a standard method of cataloguing, recovery, and running different data queries. DBMS manages the input data, organizes it, and provides ways of modifying or extracting the data by its users or other programs. Managing the database is an operation that requires periodical updates, optimizing and monitoring.

  14. NV FUEL OPTIMIZER

    OpenAIRE

    Calderón de la Peña, Juan Carlos; Opgenorth, Fadi Steven; Rey, Juan Pablo; Trujillo Stefanow, Pedro José; Varela Olea, Santiago María

    2013-01-01

    Trabajo Fin de Máster de Administración y Dirección de Empresas (MBA)con un proyecto de inversión NV FUEL OPTIMIZER, un proyecto conservador, ecológico y novedoso para el sector de la automoción, estratégico para la economía española, tanto por su elevado peso en la industria, el empleo y las exportaciones, así como por su efecto sobre el sector servicios. Con el objetivo de ofrecer un producto que ayude a hacer más kilómetros sin necesidad de cambiar de coche y ayude a cuidar el medio ambien...

  15. Convex Optimization in R

    Directory of Open Access Journals (Sweden)

    Roger Koenker

    2014-09-01

    Full Text Available Convex optimization now plays an essential role in many facets of statistics. We briefly survey some recent developments and describe some implementations of these methods in R . Applications of linear and quadratic programming are introduced including quantile regression, the Huber M-estimator and various penalized regression methods. Applications to additively separable convex problems subject to linear equality and inequality constraints such as nonparametric density estimation and maximum likelihood estimation of general nonparametric mixture models are described, as are several cone programming problems. We focus throughout primarily on implementations in the R environment that rely on solution methods linked to R, like MOSEK by the package Rmosek. Code is provided in R to illustrate several of these problems. Other applications are available in the R package REBayes, dealing with empirical Bayes estimation of nonparametric mixture models.

  16. Optimal reconstruction angles

    International Nuclear Information System (INIS)

    Cook, G.O. Jr.; Knight, L.

    1979-07-01

    The question of optimal projection angles has recently become of interest in the field of reconstruction from projections. Here, studies are concentrated on the n x n pixel space, where literative algorithms such as ART and direct matrix techniques due to Katz are considered. The best angles are determined in a Gauss--Markov statistical sense as well as with respect to a function-theoretical error bound. The possibility of making photon intensity a function of angle is also examined. Finally, the best angles to use in an ART-like algorithm are studied. A certain set of unequally spaced angles was found to be preferred in several contexts. 15 figures, 6 tables

  17. Power, control and optimization

    CERN Document Server

    Vasant, Pandian; Barsoum, Nader

    2013-01-01

    The book consists of chapters based on selected papers of international conference „Power, Control and Optimization 2012”, held in Las Vegas, USA. Readers can find interesting chapters discussing various topics from the field of power control, its distribution and related fields. Book discusses topics like energy consumption impacted by climate, mathematical modeling of the influence of thermal power plant on the aquatic environment, investigation of cost reduction in residential electricity bill using electric vehicle at peak times or allocation and size evaluation of distributed generation using ANN model and others.  Chapter authors are to the best of our knowledge the originators or closely related to the originators of presented ideas and its applications. Hence, this book certainly is one of the few books discussing the benefit from intersection of those modern and fruitful scientific fields of research with very tight and deep impact on real life and industry. This book is devoted to the studies o...

  18. Transpetrol and undue optimism

    International Nuclear Information System (INIS)

    Beer, G.; Slovak, K.

    2006-01-01

    We will get Transpetrol Lubomir Jahnatek, the Minister of Economy, was full of optimism following negotiations with the representatives of the Dutch company, Yukos Finance. According to the results of the meetings, the shares should have been back in Slovakia by the end of August. This enthusiasm was premature. The negotiating power of the delegation which came to Bratislava to promise the return of Transpetrol was very weak. The managers of Yukos Finance thought they would manage to avoid communication with Eduard Rebgun, Yukos' Russian bankruptcy supervisor. Their analyses showed that Yukos Finance is legally only marginally connected with the parent company, Yukos, and that they will be able to decide on the sale of Transpetrol and the Latvian refinery, Mazeikiu Nafta, on their own. On Friday last week, the Dutch courts decided that the Russian administrator is authorized to call an extraordinary general meeting of the Dutch company and to replace its management. This has further complicated the entire situation. (authors)

  19. Optimization of radiation protection

    International Nuclear Information System (INIS)

    Li Deping

    1988-01-01

    The basic concept of 'As Low As Reasonably Achievable' is explained. It takes linear non-threshold dose-effect relationship as a prudent assumption, but its application are not strictly limited to this case. Cost-benefit analysis and impementation of quantitative optimization are discussed. It is emphasized that cost-benefit analysis should be based on sound cost effectiveness analysis. The importance of the capability of prediciting the collective dose due to a specified operation and feed back from operators to designers are pointed out. The critical value α of the specific cost is discussed. The limitations of the suggestion that a lower limit of α should be proportional to the gross national product per capita is explained as it comes from a simple pure economic consideration. Attemps to adopt such value is citicized. Some functional relationship between cost and effectiveness are examined

  20. Puncture panel optimization

    International Nuclear Information System (INIS)

    Glass, R.E.; Longenbaugh, R.S.

    1986-01-01

    Sandia National Laboratories developed the TRansUranic PACkage Transporter (TRUPACT) to transport defense contact-handled transuranic wastes. The package has been designed to meet the normal and hypothetical accident conditions in 10CFR71 which includes the demonstrated ability to survive a 1-meter drop onto a mild steel pin. The puncture protection is provided by puncture resistant panels. In conjunction with the development of TRUPACT, a series of experiments has been conducted to reduce the weight of the puncture resistant panels. The initial scoping tests resulted in a preliminary design incorporating 30 layers of Kevlar. This design has been shown to meet the regulatory puncture test. To reduce the weight of this panel, subscale tests were conducted on panels utilizing Kevlar yarns with varying mass per unit length (denier) as well as different resins. This paper reviews the testing undertaken in the original panel development and discusses the results obtained from the recent subscale and full-scale optimization tests

  1. OPTIMAL NETWORK TOPOLOGY DESIGN

    Science.gov (United States)

    Yuen, J. H.

    1994-01-01

    This program was developed as part of a research study on the topology design and performance analysis for the Space Station Information System (SSIS) network. It uses an efficient algorithm to generate candidate network designs (consisting of subsets of the set of all network components) in increasing order of their total costs, and checks each design to see if it forms an acceptable network. This technique gives the true cost-optimal network, and is particularly useful when the network has many constraints and not too many components. It is intended that this new design technique consider all important performance measures explicitly and take into account the constraints due to various technical feasibilities. In the current program, technical constraints are taken care of by the user properly forming the starting set of candidate components (e.g. nonfeasible links are not included). As subsets are generated, they are tested to see if they form an acceptable network by checking that all requirements are satisfied. Thus the first acceptable subset encountered gives the cost-optimal topology satisfying all given constraints. The user must sort the set of "feasible" link elements in increasing order of their costs. The program prompts the user for the following information for each link: 1) cost, 2) connectivity (number of stations connected by the link), and 3) the stations connected by that link. Unless instructed to stop, the program generates all possible acceptable networks in increasing order of their total costs. The program is written only to generate topologies that are simply connected. Tests on reliability, delay, and other performance measures are discussed in the documentation, but have not been incorporated into the program. This program is written in PASCAL for interactive execution and has been implemented on an IBM PC series computer operating under PC DOS. The disk contains source code only. This program was developed in 1985.

  2. Public optimism towards nanomedicine.

    Science.gov (United States)

    Bottini, Massimo; Rosato, Nicola; Gloria, Fulvia; Adanti, Sara; Corradino, Nunziella; Bergamaschi, Antonio; Magrini, Andrea

    2011-01-01

    Previous benefit-risk perception studies and social experiences have clearly demonstrated that any emerging technology platform that ignores benefit-risk perception by citizens might jeopardize its public acceptability and further development. The aim of this survey was to investigate the Italian judgment on nanotechnology and which demographic and heuristic variables were most influential in shaping public perceptions of the benefits and risks of nanotechnology. In this regard, we investigated the role of four demographic (age, gender, education, and religion) and one heuristic (knowledge) predisposing factors. The present study shows that gender, education, and knowledge (but not age and religion) influenced the Italian perception of how nanotechnology will (positively or negatively) affect some areas of everyday life in the next twenty years. Furthermore, the picture that emerged from our study is that Italian citizens, despite minimal familiarity with nanotechnology, showed optimism towards nanotechnology applications, especially those related to health and medicine (nanomedicine). The high regard for nanomedicine was tied to the perception of risks associated with environmental and societal implications (division among social classes and increased public expenses) rather than health issues. However, more highly educated people showed greater concern for health issues but this did not decrease their strong belief about the benefits that nanotechnology would bring to medical fields. The results reported here suggest that public optimism towards nanomedicine appears to justify increased scientific effort and funding for medical applications of nanotechnology. It also obligates toxicologists, politicians, journalists, entrepreneurs, and policymakers to establish a more responsible dialog with citizens regarding the nature and implications of this emerging technology platform.

  3. Optimization of radiation therapy

    International Nuclear Information System (INIS)

    Ohtsubo, Masaaki

    1990-01-01

    In radiotherapy, dose optimization is to give adequate dose uniformly over target volume and minimize the dose to normal and adjacent critical organs. Therefore, it is necessary to analyze dose distribution in detail. This paper presents a method for quantitatively assessing treatment planning by analysis of dose distribution. For this purpose, several parameters were introduced, such as D T, min (minimum target absorbed dose), NUF (nonuniformity factor), volume rate of damaged lung and spinal cord, R T/T (ratio of target volume to treatment volume), LE (local efficiency), integral dose, etc. And some criteria were made using these parameters, and were applied to evaluate various plans in external beam radiation therapy for lung and esophagus cancer. In these parameters, NUF was especially useful to obtain three-dimensional dose information of target volume, and value of NUF was in agreement with the information provided by dose volume histogram. AP-PA parallel opposed fields technique was inferior in D T,min and NUF. In lung cancer, there was no spinal cord injury in oblique parallel opposed fields technique, and this technique is particularly useful when target volume is in posterior. In these two techniques, R T/T was small and hot spots were frequently observed. R T/T was largest in oblique wedged two-fields technique, but this technique was inferior in D T, min and NUF. About D T, min and NUF, four fields technique was the best, but in this technique spinal cord complication often occurred in case that target volume was in the middle. In moving beam technique (360deg rotation or arc), integral dose is large, and the more target volume is in posterior, the more often spinal cord complication occurs. In esophageal cancer, three fields technique was the best to avoid spinal cord injury. It seems that this method is very useful for optimization in radiation treatment planning. (author)

  4. Portfolio optimization retail investor

    Directory of Open Access Journals (Sweden)

    I. А. Kiseleva

    2016-01-01

    Full Text Available The article notes that the task of the investor's risk management is to, on the one hand, as much as possible to strive to achieve the criterion of risk level, and on the other hand, in any case not exceed it. Since the domestic theory of risk management is under development, the problem of the optimal ratio of "risk-income" becomes now of particular relevance. This article discusses the different distribution areas of the private investor in order to obtain the maximum profit. The analysis showed us the overall economic and political system of the country, as well as the legislative provision of guarantees to the investor. To obtain sufficient income and reduce losses it is important to maintain the optimum value found between the amount of the investor's risk and capital transactions. Model of optimal placement of funds led to the conclusion about inexpediency strong increase in the diversification of the investment portfolio (more than 10 different types of assets in the portfolio, since it increases the complexity of its practical form, while the portfolio characteristics are improved significantly. It is concluded that it is impossible to increase revenue without increasing the risk or reduce risk without reducing income. The analysis shows that there is no single best asset portfolio. It is impossible to increase revenue without increasing the risk or reduce risk without reducing income. Possible combination of the "riskincome" will depend on the objective function. Most diversified and bringing the best return per unit of risk, is a portfolio that contains the most risky assets.

  5. A hybrid bird mating optimizer algorithm with teaching-learning-based optimization for global numerical optimization

    Directory of Open Access Journals (Sweden)

    Qingyang Zhang

    2015-02-01

    Full Text Available Bird Mating Optimizer (BMO is a novel meta-heuristic optimization algorithm inspired by intelligent mating behavior of birds. However, it is still insufficient in convergence of speed and quality of solution. To overcome these drawbacks, this paper proposes a hybrid algorithm (TLBMO, which is established by combining the advantages of Teaching-learning-based optimization (TLBO and Bird Mating Optimizer (BMO. The performance of TLBMO is evaluated on 23 benchmark functions, and compared with seven state-of-the-art approaches, namely BMO, TLBO, Artificial Bee Bolony (ABC, Particle Swarm Optimization (PSO, Fast Evolution Programming (FEP, Differential Evolution (DE, Group Search Optimization (GSO. Experimental results indicate that the proposed method performs better than other existing algorithms for global numerical optimization.

  6. Constrained Optimization and Optimal Control for Partial Differential Equations

    CERN Document Server

    Leugering, Günter; Griewank, Andreas

    2012-01-01

    This special volume focuses on optimization and control of processes governed by partial differential equations. The contributors are mostly participants of the DFG-priority program 1253: Optimization with PDE-constraints which is active since 2006. The book is organized in sections which cover almost the entire spectrum of modern research in this emerging field. Indeed, even though the field of optimal control and optimization for PDE-constrained problems has undergone a dramatic increase of interest during the last four decades, a full theory for nonlinear problems is still lacking. The cont

  7. Optimal PMU Placement By Improved Particle Swarm Optimization

    DEFF Research Database (Denmark)

    Rather, Zakir Hussain; Liu, Leo; Chen, Zhe

    2013-01-01

    This paper presents an improved method of binary particle swarm optimization (IBPSO) technique for optimal phasor measurement unit (PMU) placement in a power network for complete system observability. Various effective improvements have been proposed to enhance the efficiency and convergence rate...... of conventional particle swarm optimization method. The proposed method of IBPSO ensures optimal PMU placement with and without consideration of zero injection measurements. The proposed method has been applied to standard test systems like 17 bus, IEEE 24-bus, IEEE 30-bus, New England 39-bus, IEEE 57-bus system...

  8. Optimization of mechanical structures using particle swarm optimization

    International Nuclear Information System (INIS)

    Leite, Victor C.; Schirru, Roberto

    2015-01-01

    Several optimization problems are dealed with the particle swarm optimization (PSO) algorithm, there is a wide kind of optimization problems, it may be applications related to logistics or the reload of nuclear reactors. This paper discusses the use of the PSO in the treatment of problems related to mechanical structure optimization. The geometry and material characteristics of mechanical components are important for the proper functioning and performance of the systems were they are applied, particularly to the nuclear field. Calculations related to mechanical aspects are all made using ANSYS, while the PSO is programed in MATLAB. (author)

  9. Optimization of mechanical structures using particle swarm optimization

    Energy Technology Data Exchange (ETDEWEB)

    Leite, Victor C.; Schirru, Roberto, E-mail: victor.coppo.leite@lmp.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (LMP/PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Monitoracao de Processos

    2015-07-01

    Several optimization problems are dealed with the particle swarm optimization (PSO) algorithm, there is a wide kind of optimization problems, it may be applications related to logistics or the reload of nuclear reactors. This paper discusses the use of the PSO in the treatment of problems related to mechanical structure optimization. The geometry and material characteristics of mechanical components are important for the proper functioning and performance of the systems were they are applied, particularly to the nuclear field. Calculations related to mechanical aspects are all made using ANSYS, while the PSO is programed in MATLAB. (author)

  10. Optimal Design and Related Areas in Optimization and Statistics

    CERN Document Server

    Pronzato, Luc

    2009-01-01

    This edited volume, dedicated to Henry P. Wynn, reflects his broad range of research interests, focusing in particular on the applications of optimal design theory in optimization and statistics. It covers algorithms for constructing optimal experimental designs, general gradient-type algorithms for convex optimization, majorization and stochastic ordering, algebraic statistics, Bayesian networks and nonlinear regression. Written by leading specialists in the field, each chapter contains a survey of the existing literature along with substantial new material. This work will appeal to both the

  11. Topology optimization under stochastic stiffness

    Science.gov (United States)

    Asadpoure, Alireza

    Topology optimization is a systematic computational tool for optimizing the layout of materials within a domain for engineering design problems. It allows variation of structural boundaries and connectivities. This freedom in the design space often enables discovery of new, high performance designs. However, solutions obtained by performing the optimization in a deterministic setting may be impractical or suboptimal when considering real-world engineering conditions with inherent variabilities including (for example) variabilities in fabrication processes and operating conditions. The aim of this work is to provide a computational methodology for topology optimization in the presence of uncertainties associated with structural stiffness, such as uncertain material properties and/or structural geometry. Existing methods for topology optimization under deterministic conditions are first reviewed. Modifications are then proposed to improve the numerical performance of the so-called Heaviside Projection Method (HPM) in continuum domains. Next, two approaches, perturbation and Polynomial Chaos Expansion (PCE), are proposed to account for uncertainties in the optimization procedure. These approaches are intrusive, allowing tight and efficient coupling of the uncertainty quantification with the optimization sensitivity analysis. The work herein develops a robust topology optimization framework aimed at reducing the sensitivity of optimized solutions to uncertainties. The perturbation-based approach combines deterministic topology optimization with a perturbation method for the quantification of uncertainties. The use of perturbation transforms the problem of topology optimization under uncertainty to an augmented deterministic topology optimization problem. The PCE approach combines the spectral stochastic approach for the representation and propagation of uncertainties with an existing deterministic topology optimization technique. The resulting compact representations

  12. Stiffened Composite Fuselage Barrel Optimization

    Science.gov (United States)

    Movva, R. G.; Mittal, A.; Agrawal, K.; Upadhyay, C. S.

    2012-07-01

    In a typical commercial transport aircraft, Stiffened skin panels and frames contribute around 40% of the fuselage weight. In the current study a stiffened composite fuselage skin panel optimization engine is developed for optimization of the layups of composite panels and stringers using Genetic Algorithm (GA). The skin and stringers of the fuselage section are optimized for the strength and the stability requirements. The selection of the GA parameters considered for the optimization is arrived by performing case studies on selected problems. The optimization engine facilitates in carrying out trade studies for selection of the optimum ply layup and material combination for the configuration being analyzed. The optimization process is applied on a sample model and the results are presented.

  13. Recent advances in computational optimization

    CERN Document Server

    2013-01-01

    Optimization is part of our everyday life. We try to organize our work in a better way and optimization occurs in minimizing time and cost or the maximization of the profit, quality and efficiency. Also many real world problems arising in engineering, economics, medicine and other domains can be formulated as optimization tasks. This volume is a comprehensive collection of extended contributions from the Workshop on Computational Optimization. This book presents recent advances in computational optimization. The volume includes important real world problems like parameter settings for con- trolling processes in bioreactor, robot skin wiring, strip packing, project scheduling, tuning of PID controller and so on. Some of them can be solved by applying traditional numerical methods, but others need a huge amount of computational resources. For them it is shown that is appropriate to develop algorithms based on metaheuristic methods like evolutionary computation, ant colony optimization, constrain programming etc...

  14. Optimal patent policies: A survey

    DEFF Research Database (Denmark)

    Poulsen, Odile

    2002-01-01

    This paper surveys some of the patent literature, in particular, it focuses on optimal patent policies. We compare two situations. The first where the government only has a single policy tool to design the optimal patent policy, namely the optimal patent length. In the second situation......, the government uses two policy tools, the optimal breadth and length. We show that theoretical models give very different answers to what is the optimal patent policy. In particular, we show that the optimal patent policy depends among othet things on the price elasticity of demand, the intersectoral elasticity...... of research outputs as well as the degree of compettition in the R&D sector. The actual law on intellectual property, which advocates a unique patent length of 20 years is in general not supported by theoretical models....

  15. Structural Optimization with Reliability Constraints

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    1986-01-01

    During the last 25 years considerable progress has been made in the fields of structural optimization and structural reliability theory. In classical deterministic structural optimization all variables are assumed to be deterministic. Due to the unpredictability of loads and strengths of actual......]. In this paper we consider only structures which can be modelled as systems of elasto-plastic elements, e.g. frame and truss structures. In section 2 a method to evaluate the reliability of such structural systems is presented. Based on a probabilistic point of view a modern structural optimization problem...... is formulated in section 3. The formulation is a natural extension of the commonly used formulations in determinstic structural optimization. The mathematical form of the optimization problem is briefly discussed. In section 4 two new optimization procedures especially designed for the reliability...

  16. Optimal management strategies in variable environments: Stochastic optimal control methods

    Science.gov (United States)

    Williams, B.K.

    1985-01-01

    Dynamic optimization was used to investigate the optimal defoliation of salt desert shrubs in north-western Utah. Management was formulated in the context of optimal stochastic control theory, with objective functions composed of discounted or time-averaged biomass yields. Climatic variability and community patterns of salt desert shrublands make the application of stochastic optimal control both feasible and necessary. A primary production model was used to simulate shrub responses and harvest yields under a variety of climatic regimes and defoliation patterns. The simulation results then were used in an optimization model to determine optimal defoliation strategies. The latter model encodes an algorithm for finite state, finite action, infinite discrete time horizon Markov decision processes. Three questions were addressed: (i) What effect do changes in weather patterns have on optimal management strategies? (ii) What effect does the discounting of future returns have? (iii) How do the optimal strategies perform relative to certain fixed defoliation strategies? An analysis was performed for the three shrub species, winterfat (Ceratoides lanata), shadscale (Atriplex confertifolia) and big sagebrush (Artemisia tridentata). In general, the results indicate substantial differences among species in optimal control strategies, which are associated with differences in physiological and morphological characteristics. Optimal policies for big sagebrush varied less with variation in climate, reserve levels and discount rates than did either shadscale or winterfat. This was attributed primarily to the overwintering of photosynthetically active tissue and to metabolic activity early in the growing season. Optimal defoliation of shadscale and winterfat generally was more responsive to differences in plant vigor and climate, reflecting the sensitivity of these species to utilization and replenishment of carbohydrate reserves. Similarities could be seen in the influence of both

  17. Optimizing towing processes at airports

    OpenAIRE

    Du, Jia Yan

    2015-01-01

    This work addresses the optimization of push-back and towing processes at airports, as an important part of the turnaround process. A vehicle routing based scheduling model is introduced to find a cost optimal assignment of jobs to towing tractors in daily operations. A second model derives an investment strategy to optimize tractor fleet size and mix in the long-run. Column generation heuristics are proposed as solution procedures. The thesis concludes with a case study of a major European ...

  18. Nature-inspired optimization algorithms

    CERN Document Server

    Yang, Xin-She

    2014-01-01

    Nature-Inspired Optimization Algorithms provides a systematic introduction to all major nature-inspired algorithms for optimization. The book's unified approach, balancing algorithm introduction, theoretical background and practical implementation, complements extensive literature with well-chosen case studies to illustrate how these algorithms work. Topics include particle swarm optimization, ant and bee algorithms, simulated annealing, cuckoo search, firefly algorithm, bat algorithm, flower algorithm, harmony search, algorithm analysis, constraint handling, hybrid methods, parameter tuning

  19. Optimization problem in quantum cryptography

    International Nuclear Information System (INIS)

    Brandt, Howard E

    2003-01-01

    A complete optimization was recently performed, yielding the maximum information gain by a general unitary entangling probe in the four-state protocol of quantum cryptography. A larger set of optimum probe parameters was found than was known previously from an incomplete optimization. In the present work, a detailed comparison is made between the complete and incomplete optimizations. Also, a new set of optimum probe parameters is identified for the four-state protocol

  20. An Optimal Lower Eigenvalue System

    Directory of Open Access Journals (Sweden)

    Yingfan Liu

    2011-01-01

    Full Text Available An optimal lower eigenvalue system is studied, and main theorems including a series of necessary and suffcient conditions concerning existence and a Lipschitz continuity result concerning stability are obtained. As applications, solvability results to some von-Neumann-type input-output inequalities, growth, and optimal growth factors, as well as Leontief-type balanced and optimal balanced growth paths, are also gotten.

  1. Professor: The Animal Planet Optimization

    OpenAIRE

    Satish Gajawada

    2014-01-01

    This paper is dedicated to everyone who is interested in making this planet a better place to live. In the past, researchers have explored behavior of several animals separately. But there is scope to explore in the direction where various artificial animals together solve the optimization problem. In this paper, Satish Gajawada proposed The AnimalPlanet Optimization. The concept of this paper is to imitate all the animals on this planet. The idea is to solve the optimization problem where al...

  2. A Parallel Particle Swarm Optimizer

    National Research Council Canada - National Science Library

    Schutte, J. F; Fregly, B .J; Haftka, R. T; George, A. D

    2003-01-01

    .... Motivated by a computationally demanding biomechanical system identification problem, we introduce a parallel implementation of a stochastic population based global optimizer, the Particle Swarm...

  3. Optimal Design of Porous Materials

    DEFF Research Database (Denmark)

    Andreassen, Erik

    The focus of this thesis is topology optimization of material microstructures. That is, creating new materials, with attractive properties, by combining classic materials in periodic patterns. First, large-scale topology optimization is used to design complicated three-dimensional materials......, throughout the thesis extra attention is given to obtain structures that can be manufactured. That is also the case in the final part, where a simple multiscale method for the optimization of structural damping is presented. The method can be used to obtain an optimized component with structural details...

  4. Portfolio optimization and performance evaluation

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Christensen, Michael

    2013-01-01

    Based on an exclusive business-to-business database comprising nearly 1,000 customers, the applicability of portfolio analysis is documented, and it is examined how such an optimization analysis can be used to explore the growth potential of a company. As opposed to any previous analyses, optimal...... customer portfolios are determined, and it is shown how marketing decision-makers can use this information in their marketing strategies to optimize the revenue growth of the company. Finally, our analysis is the first analysis which applies portfolio based methods to measure customer performance......, and it is shown how these performance measures complement the optimization analysis....

  5. Optimization methods for logical inference

    CERN Document Server

    Chandru, Vijay

    2011-01-01

    Merging logic and mathematics in deductive inference-an innovative, cutting-edge approach. Optimization methods for logical inference? Absolutely, say Vijay Chandru and John Hooker, two major contributors to this rapidly expanding field. And even though ""solving logical inference problems with optimization methods may seem a bit like eating sauerkraut with chopsticks. . . it is the mathematical structure of a problem that determines whether an optimization model can help solve it, not the context in which the problem occurs."" Presenting powerful, proven optimization techniques for logic in

  6. Optimally segmented permanent magnet structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bjørk, Rasmus; Smith, Anders

    2016-01-01

    We present an optimization approach which can be employed to calculate the globally optimal segmentation of a two-dimensional magnetic system into uniformly magnetized pieces. For each segment the algorithm calculates the optimal shape and the optimal direction of the remanent flux density vector......, with respect to a linear objective functional. We illustrate the approach with results for magnet design problems from different areas, such as a permanent magnet electric motor, a beam focusing quadrupole magnet for particle accelerators and a rotary device for magnetic refrigeration....

  7. Optimally cloned binary coherent states

    Science.gov (United States)

    Müller, C. R.; Leuchs, G.; Marquardt, Ch.; Andersen, U. L.

    2017-10-01

    Binary coherent state alphabets can be represented in a two-dimensional Hilbert space. We capitalize this formal connection between the otherwise distinct domains of qubits and continuous variable states to map binary phase-shift keyed coherent states onto the Bloch sphere and to derive their quantum-optimal clones. We analyze the Wigner function and the cumulants of the clones, and we conclude that optimal cloning of binary coherent states requires a nonlinearity above second order. We propose several practical and near-optimal cloning schemes and compare their cloning fidelity to the optimal cloner.

  8. Pro Android Apps Performance Optimization

    CERN Document Server

    Guihot, Hervé

    2012-01-01

    Today's Android apps developers are often running into the need to refine, improve and optimize their apps performances. As more complex apps can be created, it is even more important for developers to deal with this critical issue. Android allows developers to write apps using Java, C or a combination of both with the Android SDK and the Android NDK. Pro Android Apps Performance Optimization reveals how to fine-tune your Android apps, making them more stable and faster. In this book, you'll learn the following: * How to optimize your Java code with the SDK, but also how to write and optimize

  9. Characteristics for Software Optimization Projects

    Directory of Open Access Journals (Sweden)

    Iulian NITESCU

    2008-01-01

    Full Text Available The increasing of the software systems complexity imposes the identification and implementation of some methods and techniques in order to manage it. The software optimization project is a way in which the software complexity is controlled. The software optimization project must face to the organization need to earn profit. The software optimization project is an integrated part of the application cycle because share same resources, depends on other stages and influences next phases. The optimization project has some particularities because it works on an finished product around its quality. The process is quality and performance oriented and it assumes that the product life cycle is almost finished.

  10. On the efficiency of chaos optimization algorithms for global optimization

    International Nuclear Information System (INIS)

    Yang Dixiong; Li Gang; Cheng Gengdong

    2007-01-01

    Chaos optimization algorithms as a novel method of global optimization have attracted much attention, which were all based on Logistic map. However, we have noticed that the probability density function of the chaotic sequences derived from Logistic map is a Chebyshev-type one, which may affect the global searching capacity and computational efficiency of chaos optimization algorithms considerably. Considering the statistical property of the chaotic sequences of Logistic map and Kent map, the improved hybrid chaos-BFGS optimization algorithm and the Kent map based hybrid chaos-BFGS algorithm are proposed. Five typical nonlinear functions with multimodal characteristic are tested to compare the performance of five hybrid optimization algorithms, which are the conventional Logistic map based chaos-BFGS algorithm, improved Logistic map based chaos-BFGS algorithm, Kent map based chaos-BFGS algorithm, Monte Carlo-BFGS algorithm, mesh-BFGS algorithm. The computational performance of the five algorithms is compared, and the numerical results make us question the high efficiency of the chaos optimization algorithms claimed in some references. It is concluded that the efficiency of the hybrid optimization algorithms is influenced by the statistical property of chaotic/stochastic sequences generated from chaotic/stochastic algorithms, and the location of the global optimum of nonlinear functions. In addition, it is inappropriate to advocate the high efficiency of the global optimization algorithms only depending on several numerical examples of low-dimensional functions

  11. Optimism and Adaptation to Multiple Sclerosis: What Does Optimism Mean?

    NARCIS (Netherlands)

    Fournier, M.; Ridder, D.T.D. de; Bensing, J.

    1999-01-01

    The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaire s (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires.

  12. Optimism and adaptation to multiple sclerosis: what does optimism mean?

    NARCIS (Netherlands)

    Fournier, M.; Ridder, D. de; Bensing, J.

    1999-01-01

    The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaires (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires. In

  13. Binary Cockroach Swarm Optimization for Combinatorial Optimization Problem

    Directory of Open Access Journals (Sweden)

    Ibidun Christiana Obagbuwa

    2016-09-01

    Full Text Available The Cockroach Swarm Optimization (CSO algorithm is inspired by cockroach social behavior. It is a simple and efficient meta-heuristic algorithm and has been applied to solve global optimization problems successfully. The original CSO algorithm and its variants operate mainly in continuous search space and cannot solve binary-coded optimization problems directly. Many optimization problems have their decision variables in binary. Binary Cockroach Swarm Optimization (BCSO is proposed in this paper to tackle such problems and was evaluated on the popular Traveling Salesman Problem (TSP, which is considered to be an NP-hard Combinatorial Optimization Problem (COP. A transfer function was employed to map a continuous search space CSO to binary search space. The performance of the proposed algorithm was tested firstly on benchmark functions through simulation studies and compared with the performance of existing binary particle swarm optimization and continuous space versions of CSO. The proposed BCSO was adapted to TSP and applied to a set of benchmark instances of symmetric TSP from the TSP library. The results of the proposed Binary Cockroach Swarm Optimization (BCSO algorithm on TSP were compared to other meta-heuristic algorithms.

  14. Optimal investment horizons

    Science.gov (United States)

    Simonsen, I.; Jensen, M. H.; Johansen, A.

    2002-06-01

    In stochastic finance, one traditionally considers the return as a competitive measure of an asset, i.e., the profit generated by that asset after some fixed time span Δt, say one week or one year. This measures how well (or how bad) the asset performs over that given period of time. It has been established that the distribution of returns exhibits ``fat tails'' indicating that large returns occur more frequently than what is expected from standard Gaussian stochastic processes [1-3]. Instead of estimating this ``fat tail'' distribution of returns, we propose here an alternative approach, which is outlined by addressing the following question: What is the smallest time interval needed for an asset to cross a fixed return level of say 10%? For a particular asset, we refer to this time as the investment horizon and the corresponding distribution as the investment horizon distribution. This latter distribution complements that of returns and provides new and possibly crucial information for portfolio design and risk-management, as well as for pricing of more exotic options. By considering historical financial data, exemplified by the Dow Jones Industrial Average, we obtain a novel set of probability distributions for the investment horizons which can be used to estimate the optimal investment horizon for a stock or a future contract.

  15. Optimizing kaon production

    International Nuclear Information System (INIS)

    Berley, D.

    1976-01-01

    Kaon production data is examined with the view toward producing high quality beams in the future. Emphasis is placed upon the low momentum region, below 1 GeV/c, where the behavior of the kaon momentum spectrum is shown to be dominated by strongly momentum dependent kinematic factors. No complete experimental survey of production cross sections at different incident proton energies exists from a single apparatus. Information on relative production yields for different proton energies is important in the choice of parameters for an accelerator constructed primarily as a source of kaons. Data from different accelerators do exist and have been compiled. The key element in understanding how to present the data from different laboratories in a consistent way is an analysis of the effects of target material, target size, and production angle. This analysis not only enables a unification of the data but also indicates simple, useful and powerful principles about optimizing target efficiency. A summary is presented of existing kaon production facilities in the United States. These are all at proton accelerators. The possibility of using electron accelerators as kaon sources is examined. It is found that secondary beam fluxes can be obtained at electron linacs which are comparable to those obtained at proton synchrotrons

  16. Optimal background matching camouflage.

    Science.gov (United States)

    Michalis, Constantine; Scott-Samuel, Nicholas E; Gibson, David P; Cuthill, Innes C

    2017-07-12

    Background matching is the most familiar and widespread camouflage strategy: avoiding detection by having a similar colour and pattern to the background. Optimizing background matching is straightforward in a homogeneous environment, or when the habitat has very distinct sub-types and there is divergent selection leading to polymorphism. However, most backgrounds have continuous variation in colour and texture, so what is the best solution? Not all samples of the background are likely to be equally inconspicuous, and laboratory experiments on birds and humans support this view. Theory suggests that the most probable background sample (in the statistical sense), at the size of the prey, would, on average, be the most cryptic. We present an analysis, based on realistic assumptions about low-level vision, that estimates the distribution of background colours and visual textures, and predicts the best camouflage. We present data from a field experiment that tests and supports our predictions, using artificial moth-like targets under bird predation. Additionally, we present analogous data for humans, under tightly controlled viewing conditions, searching for targets on a computer screen. These data show that, in the absence of predator learning, the best single camouflage pattern for heterogeneous backgrounds is the most probable sample. © 2017 The Authors.

  17. Mathematics of optimization

    CERN Document Server

    Miller, Steven J

    2017-01-01

    Optimization Theory is an active area of research with numerous applications; many of the books are designed for engineering classes, and thus have an emphasis on problems from such fields. Covering much of the same material, there is less emphasis on coding and detailed applications as the intended audience is more mathematical. There are still several important problems discussed (especially scheduling problems), but there is more emphasis on theory and less on the nuts and bolts of coding. A constant theme of the text is the "why" and the "how" in the subject. Why are we able to do a calculation efficiently? How should we look at a problem? Extensive effort is made to motivate the mathematics and isolate how one can apply ideas/perspectives to a variety of problems. As many of the key algorithms in the subject require too much time or detail to analyze in a first course (such as the run-time of the Simplex Algorithm), there are numerous comparisons to simpler algorithms which students have either seen or c...

  18. CBM RICH geometry optimization

    Energy Technology Data Exchange (ETDEWEB)

    Mahmoud, Tariq; Hoehne, Claudia [II. Physikalisches Institut, Giessen Univ. (Germany); Collaboration: CBM-Collaboration

    2016-07-01

    The Compressed Baryonic Matter (CBM) experiment at the future FAIR complex will investigate the phase diagram of strongly interacting matter at high baryon density and moderate temperatures in A+A collisions from 2-11 AGeV (SIS100) beam energy. The main electron identification detector in the CBM experiment will be a RICH detector with a CO{sub 2} gaseous-radiator, focusing spherical glass mirrors, and MAPMT photo-detectors being placed on a PMT-plane. The RICH detector is located directly behind the CBM dipole magnet. As the final magnet geometry is now available, some changes in the RICH geometry become necessary. In order to guarantee a magnetic field of 1 mT at maximum in the PMT plane for effective operation of the MAPMTs, two measures have to be taken: The PMT plane is moved outwards of the stray field by tilting the mirrors by 10 degrees and shielding boxes have been designed. In this contribution the results of the geometry optimization procedure are presented.

  19. Particle swarm optimization: an alternative in marine propeller optimization?

    Science.gov (United States)

    Vesting, F.; Bensow, R. E.

    2018-01-01

    This article deals with improving and evaluating the performance of two evolutionary algorithm approaches for automated engineering design optimization. Here a marine propeller design with constraints on cavitation nuisance is the intended application. For this purpose, the particle swarm optimization (PSO) algorithm is adapted for multi-objective optimization and constraint handling for use in propeller design. Three PSO algorithms are developed and tested for the optimization of four commercial propeller designs for different ship types. The results are evaluated by interrogating the generation medians and the Pareto front development. The same propellers are also optimized utilizing the well established NSGA-II genetic algorithm to provide benchmark results. The authors' PSO algorithms deliver comparable results to NSGA-II, but converge earlier and enhance the solution in terms of constraints violation.

  20. Ant colony search algorithm for optimal reactive power optimization

    Directory of Open Access Journals (Sweden)

    Lenin K.

    2006-01-01

    Full Text Available The paper presents an (ACSA Ant colony search Algorithm for Optimal Reactive Power Optimization and voltage control of power systems. ACSA is a new co-operative agents’ approach, which is inspired by the observation of the behavior of real ant colonies on the topic of ant trial formation and foraging methods. Hence, in the ACSA a set of co-operative agents called "Ants" co-operates to find good solution for Reactive Power Optimization problem. The ACSA is applied for optimal reactive power optimization is evaluated on standard IEEE, 30, 57, 191 (practical test bus system. The proposed approach is tested and compared to genetic algorithm (GA, Adaptive Genetic Algorithm (AGA.

  1. Hybrid Optimization Algorithm of Particle Swarm Optimization and Cuckoo Search for Preventive Maintenance Period Optimization

    Directory of Open Access Journals (Sweden)

    Jianwen Guo

    2016-01-01

    Full Text Available All equipment must be maintained during its lifetime to ensure normal operation. Maintenance is one of the critical roles in the success of manufacturing enterprises. This paper proposed a preventive maintenance period optimization model (PMPOM to find an optimal preventive maintenance period. By making use of the advantages of particle swarm optimization (PSO and cuckoo search (CS algorithm, a hybrid optimization algorithm of PSO and CS is proposed to solve the PMPOM problem. The test functions show that the proposed algorithm exhibits more outstanding performance than particle swarm optimization and cuckoo search. Experiment results show that the proposed algorithm has advantages of strong optimization ability and fast convergence speed to solve the PMPOM problem.

  2. Global optimization and simulated annealing

    NARCIS (Netherlands)

    Dekkers, A.; Aarts, E.H.L.

    1988-01-01

    In this paper we are concerned with global optimization, which can be defined as the problem of finding points on a bounded subset of Rn in which some real valued functionf assumes its optimal (i.e. maximal or minimal) value. We present a stochastic approach which is based on the simulated annealing

  3. Conceptual optimal design of jackets

    DEFF Research Database (Denmark)

    Sandal, Kasper; Verbart, Alexander; Stolpe, Mathias

    Structural optimization can explore a large design space (400 jackets) in a short time (2 hours), and thus lead to better conceptual jacket designs.......Structural optimization can explore a large design space (400 jackets) in a short time (2 hours), and thus lead to better conceptual jacket designs....

  4. Accelerating ROP detector layout optimization

    International Nuclear Information System (INIS)

    Kastanya, D.; Fodor, B.

    2012-01-01

    The ADORE (Alternating Detector layout Optimization for REgional overpower protection system) algorithm for performing the optimization of regional overpower protection (ROP) system for CANDU® reactors have been recently developed. The simulated annealing (SA) stochastic optimization technique is utilized to come up with a quasi optimized detector layout for the ROP systems. Within each simulated annealing history, the objective function is calculated as a function of the trip set point (TSP) corresponding to the detector layout for that particular history. The evaluation of the TSP is done probabilistically using the ROVER-F code. Since during each optimization execution thousands of candidate detector layouts are evaluated, the overall optimization process is time consuming. Since for each ROVER-F evaluation the number of fuelling ripples controls the execution time, reducing the number of fuelling ripples used during the calculation of TSP will reduce the overall optimization execution time. This approach has been investigated and the results are presented in this paper. The challenge is to construct a set of representative fuelling ripples which will significantly speedup the optimization process while guaranteeing that the resulting detector layout has similar quality to the ones produced when the complete set of fuelling ripples is employed. Results presented in this paper indicate that a speedup of up to around 40 times is attainable when this approach is utilized. (author)

  5. Design of an Optimal Biorefinery

    DEFF Research Database (Denmark)

    Nawaz, Muhammad; Zondervan, Edwin; Woodley, John

    2011-01-01

    In this paper we propose a biorefinery optimization model that can be used to find the optimal processing route for the production of ethanol, butanol, succinic acid and blends of these chemicals with fossil fuel based gasoline. The approach unites transshipment models with a superstructure...

  6. Topology optimization of turbulent flows

    DEFF Research Database (Denmark)

    Dilgen, Cetin B.; Dilgen, Sumer B.; Fuhrman, David R.

    2018-01-01

    The aim of this work is to present a fast and viable approach for taking into account turbulence in topology optimization of complex fluid flow systems, without resorting to any simplifying assumptions in the derivation of discrete adjoints. Topology optimization is an iterative gradient...

  7. Approximate Reanalysis in Topology Optimization

    DEFF Research Database (Denmark)

    Amir, Oded; Bendsøe, Martin P.; Sigmund, Ole

    2009-01-01

    In the nested approach to structural optimization, most of the computational effort is invested in the solution of the finite element analysis equations. In this study, the integration of an approximate reanalysis procedure into the framework of topology optimization of continuum structures...

  8. Supply-Chain Optimization Template

    Science.gov (United States)

    Quiett, William F.; Sealing, Scott L.

    2009-01-01

    The Supply-Chain Optimization Template (SCOT) is an instructional guide for identifying, evaluating, and optimizing (including re-engineering) aerospace- oriented supply chains. The SCOT was derived from the Supply Chain Council s Supply-Chain Operations Reference (SCC SCOR) Model, which is more generic and more oriented toward achieving a competitive advantage in business.

  9. Sensitivity analysis in dynamic optimization

    NARCIS (Netherlands)

    Evers, A.H.

    1980-01-01

    To find the optimal control of chemical processes, Pontryagin's minimum principle can be used. In practice, however, one is not only interested in the optimal solution, which satisfies the restrictions on the control, the initial and terminal conditions, and the process parameters. It is also

  10. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas; Holzwarth, Natalie

    2009-01-01

    A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used.......A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used....

  11. Quantum information and convex optimization

    International Nuclear Information System (INIS)

    Reimpell, Michael

    2008-01-01

    This thesis is concerned with convex optimization problems in quantum information theory. It features an iterative algorithm for optimal quantum error correcting codes, a postprocessing method for incomplete tomography data, a method to estimate the amount of entanglement in witness experiments, and it gives necessary and sufficient criteria for the existence of retrodiction strategies for a generalized mean king problem. (orig.)

  12. A Problem on Optimal Transportation

    Science.gov (United States)

    Cechlarova, Katarina

    2005-01-01

    Mathematical optimization problems are not typical in the classical curriculum of mathematics. In this paper we show how several generalizations of an easy problem on optimal transportation were solved by gifted secondary school pupils in a correspondence mathematical seminar, how they can be used in university courses of linear programming and…

  13. Optimal Investment in Structured Bonds

    DEFF Research Database (Denmark)

    Jessen, Pernille; Jørgensen, Peter Løchte

    The paper examines the role of structured bonds in the optimal portfolio of a small retail investor. We consider the typical structured bond essentially repacking an exotic option and a zero coupon bond, i.e. an investment with portfolio insurance. The optimal portfolio is found when the investment...

  14. Optimal admission to higher education

    DEFF Research Database (Denmark)

    Albæk, Karsten

    2016-01-01

    that documents the relevance of theory and illustrates how to apply optimal admission procedures. Indirect gains from optimal admission procedures include the potential for increasing entire cohorts of students' probability of graduating with a higher education degree, thereby increasing the skill level...

  15. Non-euclidean simplex optimization

    International Nuclear Information System (INIS)

    Silver, G.L.

    1977-01-01

    Geometric optimization techniques useful for studying chemical equilibrium traditionally rely upon principles of euclidean geometry, but such algorithms may also be based upon principles of a non-euclidean geometry. The sequential simplex method is adapted to the hyperbolic plane, and application of optimization to problems such as the potentiometric titration of plutonium is suggested

  16. Quantum information and convex optimization

    Energy Technology Data Exchange (ETDEWEB)

    Reimpell, Michael

    2008-07-01

    This thesis is concerned with convex optimization problems in quantum information theory. It features an iterative algorithm for optimal quantum error correcting codes, a postprocessing method for incomplete tomography data, a method to estimate the amount of entanglement in witness experiments, and it gives necessary and sufficient criteria for the existence of retrodiction strategies for a generalized mean king problem. (orig.)

  17. Efficient AUC optimization for classification

    NARCIS (Netherlands)

    Calders, T.; Jaroszewicz, S.; Kok, J.N.; Koronacki, J.; Lopez de Mantaras, R.; Matwin, S.; Mladenic, D.; Skowron, A.

    2007-01-01

    In this paper we show an efficient method for inducing classifiers that directly optimize the area under the ROC curve. Recently, AUC gained importance in the classification community as a mean to compare the performance of classifiers. Because most classification methods do not optimize this

  18. Optimal Cash Management Under Uncertainty

    OpenAIRE

    Bensoussan, Alain; Chutani, Anshuman; Sethi, Suresh

    2009-01-01

    We solve an agent's optimization problem of meeting demands for cash over time with cash deposited in bank or invested in stock. The stock pays dividends and uncertain capital gains, and a commission is incurred in buying and selling of stock. We use a stochastic maximum principle to obtain explicitly the optimal transaction policy.

  19. Optimal Portfolio Choice with Annuitization

    NARCIS (Netherlands)

    Koijen, R.S.J.; Nijman, T.E.; Werker, B.J.M.

    2006-01-01

    We study the optimal consumption and portfolio choice problem over an individual's life-cycle taking into account annuity risk at retirement. Optimally, the investor allocates wealth at retirement to nominal, inflation-linked, and variable annuities and conditions this choice on the state of the

  20. Well-posed optimization problems

    CERN Document Server

    Dontchev, Asen L

    1993-01-01

    This book presents in a unified way the mathematical theory of well-posedness in optimization. The basic concepts of well-posedness and the links among them are studied, in particular Hadamard and Tykhonov well-posedness. Abstract optimization problems as well as applications to optimal control, calculus of variations and mathematical programming are considered. Both the pure and applied side of these topics are presented. The main subject is often introduced by heuristics, particular cases and examples. Complete proofs are provided. The expected knowledge of the reader does not extend beyond textbook (real and functional) analysis, some topology and differential equations and basic optimization. References are provided for more advanced topics. The book is addressed to mathematicians interested in optimization and related topics, and also to engineers, control theorists, economists and applied scientists who can find here a mathematical justification of practical procedures they encounter.

  1. Optimization of well field management

    DEFF Research Database (Denmark)

    Hansen, Annette Kirstine

    Groundwater is a limited but important resource for fresh water supply. Differ- ent conflicting objectives are important when operating a well field. This study investigates how the management of a well field can be improved with respect to different objectives simultaneously. A framework...... for optimizing well field man- agement using multi-objective optimization is developed. The optimization uses the Strength Pareto Evolutionary Algorithm 2 (SPEA2) to find the Pareto front be- tween the conflicting objectives. The Pareto front is a set of non-inferior optimal points and provides an important tool...... for the decision-makers. The optimization framework is tested on two case studies. Both abstract around 20,000 cubic meter of water per day, but are otherwise rather different. The first case study concerns the management of Hardhof waterworks, Switzer- land, where artificial infiltration of river water...

  2. Combined Shape and Topology Optimization

    DEFF Research Database (Denmark)

    Christiansen, Asger Nyman

    Shape and topology optimization seeks to compute the optimal shape and topology of a structure such that one or more properties, for example stiffness, balance or volume, are improved. The goal of the thesis is to develop a method for shape and topology optimization which uses the Deformable...... Simplicial Complex (DSC) method. Consequently, we present a novel method which combines current shape and topology optimization methods. This method represents the surface of the structure explicitly and discretizes the structure into non-overlapping elements, i.e. a simplicial complex. An explicit surface...... representation usually limits the optimization to minor shape changes. However, the DSC method uses a single explicit representation and still allows for large shape and topology changes. It does so by constantly applying a set of mesh operations during deformations of the structure. Using an explicit instead...

  3. Risk modelling in portfolio optimization

    Science.gov (United States)

    Lam, W. H.; Jaaman, Saiful Hafizah Hj.; Isa, Zaidi

    2013-09-01

    Risk management is very important in portfolio optimization. The mean-variance model has been used in portfolio optimization to minimize the investment risk. The objective of the mean-variance model is to minimize the portfolio risk and achieve the target rate of return. Variance is used as risk measure in the mean-variance model. The purpose of this study is to compare the portfolio composition as well as performance between the optimal portfolio of mean-variance model and equally weighted portfolio. Equally weighted portfolio means the proportions that are invested in each asset are equal. The results show that the portfolio composition of the mean-variance optimal portfolio and equally weighted portfolio are different. Besides that, the mean-variance optimal portfolio gives better performance because it gives higher performance ratio than the equally weighted portfolio.

  4. Optimal dynamic detection of explosives

    Energy Technology Data Exchange (ETDEWEB)

    Moore, David Steven [Los Alamos National Laboratory; Mcgrane, Shawn D [Los Alamos National Laboratory; Greenfield, Margo T [Los Alamos National Laboratory; Scharff, R J [Los Alamos National Laboratory; Rabitz, Herschel A [PRINCETON UNIV; Roslund, J [PRINCETON UNIV

    2009-01-01

    The detection of explosives is a notoriously difficult problem, especially at stand-off distances, due to their (generally) low vapor pressure, environmental and matrix interferences, and packaging. We are exploring optimal dynamic detection to exploit the best capabilities of recent advances in laser technology and recent discoveries in optimal shaping of laser pulses for control of molecular processes to significantly enhance the standoff detection of explosives. The core of the ODD-Ex technique is the introduction of optimally shaped laser pulses to simultaneously enhance sensitivity of explosives signatures while reducing the influence of noise and the signals from background interferents in the field (increase selectivity). These goals are being addressed by operating in an optimal nonlinear fashion, typically with a single shaped laser pulse inherently containing within it coherently locked control and probe sub-pulses. With sufficient bandwidth, the technique is capable of intrinsically providing orthogonal broad spectral information for data fusion, all from a single optimal pulse.

  5. Optimal control in thermal engineering

    CERN Document Server

    Badescu, Viorel

    2017-01-01

    This book is the first major work covering applications in thermal engineering and offering a comprehensive introduction to optimal control theory, which has applications in mechanical engineering, particularly aircraft and missile trajectory optimization. The book is organized in three parts: The first part includes a brief presentation of function optimization and variational calculus, while the second part presents a summary of the optimal control theory. Lastly, the third part describes several applications of optimal control theory in solving various thermal engineering problems. These applications are grouped in four sections: heat transfer and thermal energy storage, solar thermal engineering, heat engines and lubrication.Clearly presented and easy-to-use, it is a valuable resource for thermal engineers and thermal-system designers as well as postgraduate students.

  6. Optimization of power system operation

    CERN Document Server

    Zhu, Jizhong

    2015-01-01

    This book applies the latest applications of new technologies topower system operation and analysis, including new and importantareas that are not covered in the previous edition. Optimization of Power System Operation covers both traditional andmodern technologies, including power flow analysis, steady-statesecurity region analysis, security constrained economic dispatch,multi-area system economic dispatch, unit commitment, optimal powerflow, smart grid operation, optimal load shed, optimalreconfiguration of distribution network, power system uncertaintyanalysis, power system sensitivity analysis, analytic hierarchicalprocess, neural network, fuzzy theory, genetic algorithm,evolutionary programming, and particle swarm optimization, amongothers. New topics such as the wheeling model, multi-areawheeling, the total transfer capability computation in multipleareas, are also addressed. The new edition of this book continues to provide engineers andac demics with a complete picture of the optimization of techn...

  7. Optimal shapes of compact strings

    International Nuclear Information System (INIS)

    Maritan, A.; Micheletti, C.; Trovato, A.; Banavar, J.R.

    2000-07-01

    Optimal geometrical arrangements, such as the stacking of atoms, are of relevance in diverse disciplines. A classic problem is the determination of the optimal arrangement of spheres in three dimensions in order to achieve the highest packing fraction; only recently has it been proved that the answer for infinite systems is a face-centred-cubic lattice. This simply stated problem has had a profound impact in many areas, ranging from the crystallization and melting of atomic systems, to optimal packing of objects and subdivision of space. Here we study an analogous problem-that of determining the optimal shapes of closely packed compact strings. This problem is a mathematical idealization of situations commonly encountered in biology, chemistry and physics, involving the optimal structure of folded polymeric chains. We find that, in cases where boundary effects are not dominant, helices with a particular pitch-radius ratio are selected. Interestingly, the same geometry is observed in helices in naturally-occurring proteins. (author)

  8. Generalized massive optimal data compression

    Science.gov (United States)

    Alsing, Justin; Wandelt, Benjamin

    2018-05-01

    In this paper, we provide a general procedure for optimally compressing N data down to n summary statistics, where n is equal to the number of parameters of interest. We show that compression to the score function - the gradient of the log-likelihood with respect to the parameters - yields n compressed statistics that are optimal in the sense that they preserve the Fisher information content of the data. Our method generalizes earlier work on linear Karhunen-Loéve compression for Gaussian data whilst recovering both lossless linear compression and quadratic estimation as special cases when they are optimal. We give a unified treatment that also includes the general non-Gaussian case as long as mild regularity conditions are satisfied, producing optimal non-linear summary statistics when appropriate. As a worked example, we derive explicitly the n optimal compressed statistics for Gaussian data in the general case where both the mean and covariance depend on the parameters.

  9. Biocapacity optimization in regional planning

    Science.gov (United States)

    Guo, Jianjun; Yue, Dongxia; Li, Kai; Hui, Cang

    2017-01-01

    Ecological overshoot has been accelerating across the globe. Optimizing biocapacity has become a key to resolve the overshoot of ecological demand in regional sustainable development. However, most literature has focused on reducing ecological footprint but ignores the potential of spatial optimization of biocapacity through regional planning of land use. Here we develop a spatial probability model and present four scenarios for optimizing biocapacity of a river basin in Northwest China. The potential of enhanced biocapacity and its effects on ecological overshoot and water consumption in the region were explored. Two scenarios with no restrictions on croplands and water use reduced the overshoot by 29 to 53%, and another two scenarios which do not allow croplands and water use to increase worsened the overshoot by 11 to 15%. More spatially flexible transition rules of land use led to higher magnitude of change after optimization. However, biocapacity optimization required a large amount of additional water resources, casting considerable pressure on the already water-scarce socio-ecological system. Our results highlight the potential for policy makers to manage/optimize regional land use which addresses ecological overshoot. Investigation on the feasibility of such spatial optimization complies with the forward-looking policies for sustainable development and deserves further attention.

  10. Aircraft technology portfolio optimization using ant colony optimization

    Science.gov (United States)

    Villeneuve, Frederic J.; Mavris, Dimitri N.

    2012-11-01

    Technology portfolio selection is a combinatorial optimization problem often faced with a large number of combinations and technology incompatibilities. The main research question addressed in this article is to determine if Ant Colony Optimization (ACO) is better suited than Genetic Algorithms (GAs) and Simulated Annealing (SA) for technology portfolio optimization when incompatibility constraints between technologies are present. Convergence rate, capability to find optima, and efficiency in handling of incompatibilities are the three criteria of comparison. The application problem consists of finding the best technology portfolio from 29 aircraft technologies. The results show that ACO and GAs converge faster and find optima more easily than SA, and that ACO can optimize portfolios with technology incompatibilities without using penalty functions. This latter finding paves the way for more use of ACO when the number of constraints increases, such as in the technology and concept selection for complex engineering systems.

  11. A Novel Particle Swarm Optimization Algorithm for Global Optimization.

    Science.gov (United States)

    Wang, Chun-Feng; Liu, Kui

    2016-01-01

    Particle Swarm Optimization (PSO) is a recently developed optimization method, which has attracted interest of researchers in various areas due to its simplicity and effectiveness, and many variants have been proposed. In this paper, a novel Particle Swarm Optimization algorithm is presented, in which the information of the best neighbor of each particle and the best particle of the entire population in the current iteration is considered. Meanwhile, to avoid premature, an abandoned mechanism is used. Furthermore, for improving the global convergence speed of our algorithm, a chaotic search is adopted in the best solution of the current iteration. To verify the performance of our algorithm, standard test functions have been employed. The experimental results show that the algorithm is much more robust and efficient than some existing Particle Swarm Optimization algorithms.

  12. Optimal protocols and optimal transport in stochastic thermodynamics.

    Science.gov (United States)

    Aurell, Erik; Mejía-Monasterio, Carlos; Muratore-Ginanneschi, Paolo

    2011-06-24

    Thermodynamics of small systems has become an important field of statistical physics. Such systems are driven out of equilibrium by a control, and the question is naturally posed how such a control can be optimized. We show that optimization problems in small system thermodynamics are solved by (deterministic) optimal transport, for which very efficient numerical methods have been developed, and of which there are applications in cosmology, fluid mechanics, logistics, and many other fields. We show, in particular, that minimizing expected heat released or work done during a nonequilibrium transition in finite time is solved by the Burgers equation and mass transport by the Burgers velocity field. Our contribution hence considerably extends the range of solvable optimization problems in small system thermodynamics.

  13. Optimization strategies for discrete multi-material stiffness optimization

    DEFF Research Database (Denmark)

    Hvejsel, Christian Frier; Lund, Erik; Stolpe, Mathias

    2011-01-01

    Design of composite laminated lay-ups are formulated as discrete multi-material selection problems. The design problem can be modeled as a non-convex mixed-integer optimization problem. Such problems are in general only solvable to global optimality for small to moderate sized problems. To attack...... which numerically confirm the sought properties of the new scheme in terms of convergence to a discrete solution....

  14. Topology optimization for coated structures

    DEFF Research Database (Denmark)

    Clausen, Anders; Andreassen, Erik; Sigmund, Ole

    2015-01-01

    This paper presents new results within the design of three-dimensional (3D) coated structures using topology optimization.The work is an extension of a recently published two-dimensional (2D) method for including coatedstructures into the minimum compliance topology optimization problem. The high...... level of control over key parameters demonstrated for the 2D model can likewise be achieved in 3D. The effectiveness of the approach isdemonstrated with numerical examples, which for the 3D problems have been solved using a parallel topology optimization implementation based on the PETSc toolkit....

  15. Topology Optimization for Convection Problems

    DEFF Research Database (Denmark)

    Alexandersen, Joe

    2011-01-01

    This report deals with the topology optimization of convection problems.That is, the aim of the project is to develop, implement and examine topology optimization of purely thermal and coupled thermomechanical problems,when the design-dependent eects of convection are taken into consideration.......This is done by the use of a self-programmed FORTRAN-code, which builds on an existing 2D-plane thermomechanical nite element code implementing during the course `41525 FEM-Heavy'. The topology optimizationfeatures have been implemented from scratch, and allows the program to optimize elastostatic mechanical...

  16. OPTIMIZATION METHODS AND SEO TOOLS

    Directory of Open Access Journals (Sweden)

    Maria Cristina ENACHE

    2014-06-01

    Full Text Available SEO is the activity of optimizing Web pages or whole sites in order to make them more search engine friendly, thus getting higher positions in search results. Search engine optimization (SEO involves designing, writing, and coding a website in a way that helps to improve the volume and quality of traffic to your website from people using search engines. While Search Engine Optimization is the focus of this booklet, keep in mind that it is one of many marketing techniques. A brief overview of other marketing techniques is provided at the end of this booklet.

  17. The Theory of Optimal Taxation

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    The theory of optimal taxation has often been criticized for being of little practical policy relevance, due to a lack of robust theoretical results. This paper argues that recent advances in optimal tax theory has made that theory easier to apply and may help to explain some current trends...... in international tax policy. Covering the taxation of labour income and capital income as well as indirect taxation, the paper also illustrates how some of the key results in optimal tax theory may be derived in a simple, heuristic manner....

  18. Acoustic design by topology optimization

    DEFF Research Database (Denmark)

    Dühring, Maria Bayard; Jensen, Jakob Søndergaard; Sigmund, Ole

    2008-01-01

    To bring down noise levels in human surroundings is an important issue and a method to reduce noise by means of topology optimization is presented here. The acoustic field is modeled by Helmholtz equation and the topology optimization method is based on continuous material interpolation functions...... in the density and bulk modulus. The objective function is the squared sound pressure amplitude. First, room acoustic problems are considered and it is shown that the sound level can be reduced in a certain part of the room by an optimized distribution of reflecting material in a design domain along the ceiling...

  19. Optimal lag in dynamical investments

    OpenAIRE

    Serva, M.

    1998-01-01

    A portfolio of different stocks and a risk-less security whose composition is dynamically maintained stable by trading shares at any time step leads to a growth of the capital with a nonrandom rate. This is the key for the theory of optimal-growth investment formulated by Kelly. In presence of transaction costs, the optimal composition changes and, more important, it turns out that the frequency of transactions must be reduced. This simple observation leads to the definition of an optimal lag...

  20. Optimal Provision of Public Goods

    DEFF Research Database (Denmark)

    Kreiner, Claus Thustrup; Verdelin, Nicolaj

    2009-01-01

    There currently exist two competing approaches in the literature on the optimal provision of public goods. The standard approach highlights the importance of distortionary taxation and distributional concerns. The new approach neutralizes distributional concerns by adjusting the non-linear income...... for the optimal level of a public good without imposing strong assumptions on preferences. This formula shows that distortionary taxation may have a role to play as in the standard approach. However, the main determinants of optimal provision are completely different and the traditional formula with its emphasis...

  1. Optimal control theory an introduction

    CERN Document Server

    Kirk, Donald E

    2004-01-01

    Optimal control theory is the science of maximizing the returns from and minimizing the costs of the operation of physical, social, and economic processes. Geared toward upper-level undergraduates, this text introduces three aspects of optimal control theory: dynamic programming, Pontryagin's minimum principle, and numerical techniques for trajectory optimization.Chapters 1 and 2 focus on describing systems and evaluating their performances. Chapter 3 deals with dynamic programming. The calculus of variations and Pontryagin's minimum principle are the subjects of chapters 4 and 5, and chapter

  2. Optimal taxation with home production

    OpenAIRE

    Olovsson, Conny

    2014-01-01

    Optimal taxes for Europe and the U.S. are derived in a realistically calibrated model in which agents buy consumption goods and services and use home capital and labor to produce household services. The optimal tax rate on services is substantially lower than the tax rate on goods. Specifically, the planner cannot tax home production directly and instead lowers the tax rate on market services to increase the relative price of home production. The optimal tax rate on the return to home capital...

  3. On optimization of power production

    Energy Technology Data Exchange (ETDEWEB)

    Feltenmark, S.

    1997-01-01

    Short-term optimization of power production is treated. It concerns the problem of determining a production schedule for a power system, which minimizes the total cost of production, while satisfying various constraints. The thesis consists of an introductory chapter, four chapters that each concerns a specific problem area (economic dispatch, unit commitment, hydro power planning and cogeneration optimization), plus a chapter with relevant theory. The emphasis of the thesis is on the mathematical structures that arise in problems in this field, and how to exploit them algorithmically. A recurring theme is convexification, either implicit, by dualization, or explicit, as in our approach to hydro power optimization. 134 refs

  4. Instant PageSpeed optimization

    CERN Document Server

    Jaiswal, Sanjeev

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. Instant PageSpeed Optimization is a hands-on guide that provides a number of clear, step-by-step exercises for optimizing your websites for better performance and improving their efficiency.Instant PageSpeed Optimization is aimed at website developers and administrators who wish to make their websites load faster without any errors and consume less bandwidth. It's assumed that you will have some experience in basic web technologies like HTML, CSS3, JavaScript, and the basics of netw

  5. Optimal Control and Optimization of Stochastic Supply Chain Systems

    CERN Document Server

    Song, Dong-Ping

    2013-01-01

    Optimal Control and Optimization of Stochastic Supply Chain Systems examines its subject in the context of the presence of a variety of uncertainties. Numerous examples with intuitive illustrations and tables are provided, to demonstrate the structural characteristics of the optimal control policies in various stochastic supply chains and to show how to make use of these characteristics to construct easy-to-operate sub-optimal policies.                 In Part I, a general introduction to stochastic supply chain systems is provided. Analytical models for various stochastic supply chain systems are formulated and analysed in Part II. In Part III the structural knowledge of the optimal control policies obtained in Part II is utilized to construct easy-to-operate sub-optimal control policies for various stochastic supply chain systems accordingly. Finally, Part IV discusses the optimisation of threshold-type control policies and their robustness. A key feature of the book is its tying together of ...

  6. A New Hybrid Whale Optimizer Algorithm with Mean Strategy of Grey Wolf Optimizer for Global Optimization

    Directory of Open Access Journals (Sweden)

    Narinder Singh

    2018-03-01

    Full Text Available The quest for an efficient nature-inspired optimization technique has continued over the last few decades. In this paper, a hybrid nature-inspired optimization technique has been proposed. The hybrid algorithm has been constructed using Mean Grey Wolf Optimizer (MGWO and Whale Optimizer Algorithm (WOA. We have utilized the spiral equation of Whale Optimizer Algorithm for two procedures in the Hybrid Approach GWO (HAGWO algorithm: (i firstly, we used the spiral equation in Grey Wolf Optimizer algorithm for balance between the exploitation and the exploration process in the new hybrid approach; and (ii secondly, we also applied this equation in the whole population in order to refrain from the premature convergence and trapping in local minima. The feasibility and effectiveness of the hybrid algorithm have been tested by solving some standard benchmarks, XOR, Baloon, Iris, Breast Cancer, Welded Beam Design, Pressure Vessel Design problems and comparing the results with those obtained through other metaheuristics. The solutions prove that the newly existing hybrid variant has higher stronger stability, faster convergence rate and computational accuracy than other nature-inspired metaheuristics on the maximum number of problems and can successfully resolve the function of constrained nonlinear optimization in reality.

  7. behaved particle swarm optimization (QPSO)

    African Journals Online (AJOL)

    Administrator

    2011-06-13

    Jun 13, 2011 ... experiment results of L-glutamic acid fermentation process showed that our ... Key words: Soft-sensing model, quantum-behaved particle swarm optimization ... information about such biochemical variables is, in most practical ...

  8. Truss systems and shape optimization

    Science.gov (United States)

    Pricop, Mihai Victor; Bunea, Marian; Nedelcu, Roxana

    2017-07-01

    Structure optimization is an important topic because of its benefits and wide applicability range, from civil engineering to aerospace and automotive industries, contributing to a more green industry and life. Truss finite elements are still in use in many research/industrial codesfor their simple stiffness matrixand are naturally matching the requirements for cellular materials especially considering various 3D printing technologies. Optimality Criteria combined with Solid Isotropic Material with Penalization is the optimization method of choice, particularized for truss systems. Global locked structures areobtainedusinglocally locked lattice local organization, corresponding to structured or unstructured meshes. Post processing is important for downstream application of the method, to make a faster link to the CAD systems. To export the optimal structure in CATIA, a CATScript file is automatically generated. Results, findings and conclusions are given for two and three-dimensional cases.

  9. Aeroelastic Wingbox Stiffener Topology Optimization

    Science.gov (United States)

    Stanford, Bret K.

    2017-01-01

    This work considers an aeroelastic wingbox model seeded with run-out blade stiffeners along the skins. Topology optimization is conducted within the shell webs of the stiffeners, in order to add cutouts and holes for mass reduction. This optimization is done with a global-local approach in order to moderate the computational cost: aeroelastic loads are computed at the wing-level, but the topology and sizing optimization is conducted at the panel-level. Each panel is optimized separately under stress, buckling, and adjacency constraints, and periodically reassembled to update the trimmed aeroelastic loads. The resulting topology is baselined against a design with standard full-depth solid stiffener blades, and found to weigh 7.43% less.

  10. Optimally stopped variational quantum algorithms

    Science.gov (United States)

    Vinci, Walter; Shabani, Alireza

    2018-04-01

    Quantum processors promise a paradigm shift in high-performance computing which needs to be assessed by accurate benchmarking measures. In this article, we introduce a benchmark for the variational quantum algorithm (VQA), recently proposed as a heuristic algorithm for small-scale quantum processors. In VQA, a classical optimization algorithm guides the processor's quantum dynamics to yield the best solution for a given problem. A complete assessment of the scalability and competitiveness of VQA should take into account both the quality and the time of dynamics optimization. The method of optimal stopping, employed here, provides such an assessment by explicitly including time as a cost factor. Here, we showcase this measure for benchmarking VQA as a solver for some quadratic unconstrained binary optimization. Moreover, we show that a better choice for the cost function of the classical routine can significantly improve the performance of the VQA algorithm and even improve its scaling properties.

  11. Robust Optimization of Database Queries

    Indian Academy of Sciences (India)

    JAYANT

    2011-07-06

    Jul 6, 2011 ... Based on first-order logic. ○ Edgar ... Cost-based Query Optimizer s choice of execution plan ... Determines the values of goods shipped between nations in a time period select ..... Born: 1881 Elected: 1934 Section: Medicine.

  12. Radiation protection optimization of workers

    International Nuclear Information System (INIS)

    Lochard, J.

    1994-11-01

    This report presents the contribution of CEPN (study center on protection evaluation in nuclear area) to the Days of the French Radiation Protection Society (SFRP) on optimization of workers radiation protection in electronuclear, industrial and medical areas

  13. Topics in computational linear optimization

    DEFF Research Database (Denmark)

    Hultberg, Tim Helge

    2000-01-01

    Linear optimization has been an active area of research ever since the pioneering work of G. Dantzig more than 50 years ago. This research has produced a long sequence of practical as well as theoretical improvements of the solution techniques avilable for solving linear optimization problems...... of high quality solvers and the use of algebraic modelling systems to handle the communication between the modeller and the solver. This dissertation features four topics in computational linear optimization: A) automatic reformulation of mixed 0/1 linear programs, B) direct solution of sparse unsymmetric...... systems of linear equations, C) reduction of linear programs and D) integration of algebraic modelling of linear optimization problems in C++. Each of these topics is treated in a separate paper included in this dissertation. The efficiency of solving mixed 0-1 linear programs by linear programming based...

  14. Physical optimization of afterloading techniques

    International Nuclear Information System (INIS)

    Anderson, L.L.

    1985-01-01

    Physical optimization in brachytherapy refers to the process of determining the radioactive-source configuration which yields a desired dose distribution. In manually afterloaded intracavitary therapy for cervix cancer, discrete source strengths are selected iteratively to minimize the sum of squares of differences between trial and target doses. For remote afterloading with a stepping-source device, optimized (continuously variable) dwell times are obtained, either iteratively or analytically, to give least squares approximations to dose at an arbitrary number of points; in vaginal irradiation for endometrial cancer, the objective has included dose uniformity at applicator surface points in addition to a tapered contour of target dose at depth. For template-guided interstitial implants, seed placement at rectangular-grid mesh points may be least squares optimized within target volumes defined by computerized tomography; effective optimization is possible only for (uniform) seed strength high enough that the desired average peripheral dose is achieved with a significant fraction of empty seed locations. (orig.) [de

  15. Trends in PDE constrained optimization

    CERN Document Server

    Benner, Peter; Engell, Sebastian; Griewank, Andreas; Harbrecht, Helmut; Hinze, Michael; Rannacher, Rolf; Ulbrich, Stefan

    2014-01-01

    Optimization problems subject to constraints governed by partial differential equations (PDEs) are among the most challenging problems in the context of industrial, economical and medical applications. Almost the entire range of problems in this field of research was studied and further explored as part of the Deutsche Forschungsgemeinschaft (DFG) priority program 1253 on “Optimization with Partial Differential Equations” from 2006 to 2013. The investigations were motivated by the fascinating potential applications and challenging mathematical problems that arise in the field of PDE constrained optimization. New analytic and algorithmic paradigms have been developed, implemented and validated in the context of real-world applications. In this special volume, contributions from more than fifteen German universities combine the results of this interdisciplinary program with a focus on applied mathematics.   The book is divided into five sections on “Constrained Optimization, Identification and Control”...

  16. Optimal swimming of a sheet.

    Science.gov (United States)

    Montenegro-Johnson, Thomas D; Lauga, Eric

    2014-06-01

    Propulsion at microscopic scales is often achieved through propagating traveling waves along hairlike organelles called flagella. Taylor's two-dimensional swimming sheet model is frequently used to provide insight into problems of flagellar propulsion. We derive numerically the large-amplitude wave form of the two-dimensional swimming sheet that yields optimum hydrodynamic efficiency: the ratio of the squared swimming speed to the rate-of-working of the sheet against the fluid. Using the boundary element method, we show that the optimal wave form is a front-back symmetric regularized cusp that is 25% more efficient than the optimal sine wave. This optimal two-dimensional shape is smooth, qualitatively different from the kinked form of Lighthill's optimal three-dimensional flagellum, not predicted by small-amplitude theory, and different from the smooth circular-arc-like shape of active elastic filaments.

  17. Topology optimization of viscoelastic rectifiers

    DEFF Research Database (Denmark)

    Jensen, Kristian Ejlebjærg; Szabo, Peter; Okkels, Fridolin

    2012-01-01

    An approach for the design of microfluidic viscoelastic rectifiers is presented based on a combination of a viscoelastic model and the method of topology optimization. This presumption free approach yields a material layout topologically different from experimentally realized rectifiers...

  18. With careful optimism; Vorsichtig optimistisch

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Daniela

    2012-02-17

    While the PV industry is going strong, solar thermal conversion is still a slow-moving market. SW and W asked manufacturers about their sales in 2011 and their forecasts fro 2012. In all, there is reluctant optimism.

  19. Query optimization over crowdsourced data

    KAUST Repository

    Park, Hyunjung; Widom, Jennifer

    2013-01-01

    Deco is a comprehensive system for answering declarative queries posed over stored relational data together with data obtained on-demand from the crowd. In this paper we describe Deco's cost-based query optimizer, building on Deco's data model

  20. Partisan Optimism and Political Bargaining

    DEFF Research Database (Denmark)

    Jensen, Thomas; Madum, Andreas

    Partisan voters are optimistic about electoral outcomes: their estimates of the probability of electoral success for their party or candidate are substantially higher than the average among the electorate. This has large potential implications for political bargaining. Optimism about future...... electoral outcomes can make costly bargaining delay look more favorable, which may induce partisans to punish their party for agreeing to a compromise rather than waiting, for example by not turning out to vote. Therefore, party decision makers should take optimism among partisans into account when...... bargaining. In this paper we use game theoretic modeling to explore the implications of partisan optimism for political bargaining. We show that increased optimism among a partisan group leads to a stronger bargaining position for their party, but may hurt its electoral prospects. Another main finding...

  1. Convex analysis and global optimization

    CERN Document Server

    Tuy, Hoang

    2016-01-01

    This book presents state-of-the-art results and methodologies in modern global optimization, and has been a staple reference for researchers, engineers, advanced students (also in applied mathematics), and practitioners in various fields of engineering. The second edition has been brought up to date and continues to develop a coherent and rigorous theory of deterministic global optimization, highlighting the essential role of convex analysis. The text has been revised and expanded to meet the needs of research, education, and applications for many years to come. Updates for this new edition include: · Discussion of modern approaches to minimax, fixed point, and equilibrium theorems, and to nonconvex optimization; · Increased focus on dealing more efficiently with ill-posed problems of global optimization, particularly those with hard constraints;

  2. Multiobjective Optimization Involving Quadratic Functions

    Directory of Open Access Journals (Sweden)

    Oscar Brito Augusto

    2014-01-01

    Full Text Available Multiobjective optimization is nowadays a word of order in engineering projects. Although the idea involved is simple, the implementation of any procedure to solve a general problem is not an easy task. Evolutionary algorithms are widespread as a satisfactory technique to find a candidate set for the solution. Usually they supply a discrete picture of the Pareto front even if this front is continuous. In this paper we propose three methods for solving unconstrained multiobjective optimization problems involving quadratic functions. In the first, for biobjective optimization defined in the bidimensional space, a continuous Pareto set is found analytically. In the second, applicable to multiobjective optimization, a condition test is proposed to check if a point in the decision space is Pareto optimum or not and, in the third, with functions defined in n-dimensional space, a direct noniterative algorithm is proposed to find the Pareto set. Simple problems highlight the suitability of the proposed methods.

  3. Optimization of Laminated Composite Structures

    DEFF Research Database (Denmark)

    Henrichsen, Søren Randrup

    of the contributions of the PhD project are included in the second part of the thesis. Paper A presents a framework for free material optimization where commercially available finite element analysis software is used as analysis tool. Robust buckling optimization of laminated composite structures by including...... allows for a higher degree of tailoring of the resulting material. To enable better utilization of the composite materials, optimum design procedures can be used to assist the engineer. This PhD thesis is focused on developing numerical methods for optimization of laminated composite structures...... nonlinear analysis of structures, buckling and post-buckling analysis of structures, and formulations for optimization of structures considering stiffness, buckling, and post-buckling criteria. Lastly, descriptions, main findings, and conclusions of the papers are presented. The papers forming the basis...

  4. Scale-Independent Biomechanical Optimization

    National Research Council Canada - National Science Library

    Schutte, J. F; Koh, B; Reinbolt, J. A; Haftka, R. T; George, A; Fregly, B. J

    2003-01-01

    ...: the Particle Swarm Optimizer (PSO). They apply this method to the biomechanical system identification problem of finding positions and orientations of joint axes in body segments through the processing of experimental movement data...

  5. Optimization and industry new frontiers

    CERN Document Server

    Korotkikh, Victor

    2003-01-01

    Optimization from Human Genes to Cutting Edge Technologies The challenges faced by industry today are so complex that they can only be solved through the help and participation of optimization ex­ perts. For example, many industries in e-commerce, finance, medicine, and engineering, face several computational challenges due to the mas­ sive data sets that arise in their applications. Some of the challenges include, extended memory algorithms and data structures, new program­ ming environments, software systems, cryptographic protocols, storage devices, data compression, mathematical and statistical methods for knowledge mining, and information visualization. With advances in computer and information systems technologies, and many interdisci­ plinary efforts, many of the "data avalanche challenges" are beginning to be addressed. Optimization is the most crucial component in these efforts. Nowadays, the main task of optimization is to investigate the cutting edge frontiers of these technologies and systems ...

  6. Optimization methods in structural design

    CERN Document Server

    Rothwell, Alan

    2017-01-01

    This book offers an introduction to numerical optimization methods in structural design. Employing a readily accessible and compact format, the book presents an overview of optimization methods, and equips readers to properly set up optimization problems and interpret the results. A ‘how-to-do-it’ approach is followed throughout, with less emphasis at this stage on mathematical derivations. The book features spreadsheet programs provided in Microsoft Excel, which allow readers to experience optimization ‘hands-on.’ Examples covered include truss structures, columns, beams, reinforced shell structures, stiffened panels and composite laminates. For the last three, a review of relevant analysis methods is included. Exercises, with solutions where appropriate, are also included with each chapter. The book offers a valuable resource for engineering students at the upper undergraduate and postgraduate level, as well as others in the industry and elsewhere who are new to these highly practical techniques.Whi...

  7. Optimal selection of TLD chips

    International Nuclear Information System (INIS)

    Phung, P.; Nicoll, J.J.; Edmonds, P.; Paris, M.; Thompson, C.

    1996-01-01

    Large sets of TLD chips are often used to measure beam dose characteristics in radiotherapy. A sorting method is presented to allow optimal selection of chips from a chosen set. This method considers the variation

  8. Framework for sequential approximate optimization

    NARCIS (Netherlands)

    Jacobs, J.H.; Etman, L.F.P.; Keulen, van F.; Rooda, J.E.

    2004-01-01

    An object-oriented framework for Sequential Approximate Optimization (SAO) isproposed. The framework aims to provide an open environment for thespecification and implementation of SAO strategies. The framework is based onthe Python programming language and contains a toolbox of Python

  9. Topology Optimization of Nanophotonic Devices

    DEFF Research Database (Denmark)

    Yang, Lirong

    This thesis explores the various aspects of utilizing topology optimization in designing nanophotonic devices. Either frequency-domain or time-domain methods is used in combination with the optimization algorithms, depending on various aims of the designing problems. The frequency-domain methods...... lengthscale and flexible pulse delay are addressed to demonstrate time-domain based topology optimization’s potential in designing complicated photonic structures with specifications on the time characteristics of pulses....

  10. Learning from Experiments in Optimization

    DEFF Research Database (Denmark)

    Winthereik, Brit Ross; Jensen, Casper Bruun

    2017-01-01

    This article examines attempts by professionals in the Danish branch of the environmental NGO NatureAid to optimize their practice by developing a local standard. Describing these efforts as an experiment in optimization, we outline a post-critical alternative to critiques that centre on the redu...... of management as ‘broken up;’ as a distributed, ambient activity, variably performed by different actors using different standards....

  11. CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY

    Energy Technology Data Exchange (ETDEWEB)

    BERGMAN, T. B.; STEFANSKI, L. D.; SEELEY, P. N.; ZINSLI, L. C.; CUSACK, L. J.

    2012-09-19

    THE CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY WAS CONDUCTED TO DEVELOP AN OPTIMAL SEQUENCE OF REMEDIATION ACTIVITIES IMPLEMENTING THE CERCLA DECISION ON THE CENTRAL PLATEAU. THE STUDY DEFINES A SEQUENCE OF ACTIVITIES THAT RESULT IN AN EFFECTIVE USE OF RESOURCES FROM A STRATEGIC PERSPECTIVE WHEN CONSIDERING EQUIPMENT PROCUREMENT AND STAGING, WORKFORCE MOBILIZATION/DEMOBILIZATION, WORKFORCE LEVELING, WORKFORCE SKILL-MIX, AND OTHER REMEDIATION/DISPOSITION PROJECT EXECUTION PARAMETERS.

  12. New Optimization Algorithms in Physics

    CERN Document Server

    Hartmann, Alexander K

    2004-01-01

    Many physicists are not aware of the fact that they can solve their problems by applying optimization algorithms. Since the number of such algorithms is steadily increasing, many new algorithms have not been presented comprehensively until now. This presentation of recently developed algorithms applied in physics, including demonstrations of how they work and related results, aims to encourage their application, and as such the algorithms selected cover concepts and methods from statistical physics to optimization problems emerging in theoretical computer science.

  13. Optimal Trading with Alpha Predictors

    OpenAIRE

    Filippo Passerini; Samuel E. Vazquez

    2015-01-01

    We study the problem of optimal trading using general alpha predictors with linear costs and temporary impact. We do this within the framework of stochastic optimization with finite horizon using both limit and market orders. Consistently with other studies, we find that the presence of linear costs induces a no-trading zone when using market orders, and a corresponding market-making zone when using limit orders. We show that, when combining both market and limit orders, the problem is furthe...

  14. Optimization theory for large systems

    CERN Document Server

    Lasdon, Leon S

    2002-01-01

    Important text examines most significant algorithms for optimizing large systems and clarifying relations between optimization procedures. Much data appear as charts and graphs and will be highly valuable to readers in selecting a method and estimating computer time and cost in problem-solving. Initial chapter on linear and nonlinear programming presents all necessary background for subjects covered in rest of book. Second chapter illustrates how large-scale mathematical programs arise from real-world problems. Appendixes. List of Symbols.

  15. Topology Optimized Photonic Wire Splitters

    DEFF Research Database (Denmark)

    Frandsen, Lars Hagedorn; Borel, Peter Ingo; Jensen, Jakob Søndergaard

    2006-01-01

    Photonic wire splitters have been designed using topology optimization. The splitters have been fabricated in silicon-on-insulator material and display broadband low-loss 3dB splitting in a bandwidth larger than 100 nm.......Photonic wire splitters have been designed using topology optimization. The splitters have been fabricated in silicon-on-insulator material and display broadband low-loss 3dB splitting in a bandwidth larger than 100 nm....

  16. Optimal Advertising with Stochastic Demand

    OpenAIRE

    George E. Monahan

    1983-01-01

    A stochastic, sequential model is developed to determine optimal advertising expenditures as a function of product maturity and past advertising. Random demand for the product depends upon an aggregate measure of current and past advertising called "goodwill," and the position of the product in its life cycle measured by sales-to-date. Conditions on the parameters of the model are established that insure that it is optimal to advertise less as the product matures. Additional characteristics o...

  17. Optimal Liquidation under Stochastic Liquidity

    OpenAIRE

    Becherer, Dirk; Bilarev, Todor; Frentrup, Peter

    2016-01-01

    We solve explicitly a two-dimensional singular control problem of finite fuel type for infinite time horizon. The problem stems from the optimal liquidation of an asset position in a financial market with multiplicative and transient price impact. Liquidity is stochastic in that the volume effect process, which determines the inter-temporal resilience of the market in spirit of Predoiu, Shaikhet and Shreve (2011), is taken to be stochastic, being driven by own random noise. The optimal contro...

  18. Optimal Taxation under Income Uncertainty

    OpenAIRE

    Xianhua Dai

    2011-01-01

    Optimal taxation under income uncertainty has been extensively developed in expected utility theory, but it is still open for inseparable utility function between income and effort. As an alternative of decision-making under uncertainty, prospect theory (Kahneman and Tversky (1979), Tversky and Kahneman (1992)) has been obtained empirical support, for example, Kahneman and Tversky (1979), and Camerer and Lowenstein (2003). It is beginning to explore optimal taxation in the context of prospect...

  19. I-optimal mixture designs

    OpenAIRE

    GOOS, Peter; JONES, Bradley; SYAFITRI, Utami

    2013-01-01

    In mixture experiments, the factors under study are proportions of the ingredients of a mixture. The special nature of the factors in a mixture experiment necessitates specific types of regression models, and specific types of experimental designs. Although mixture experiments usually are intended to predict the response(s) for all possible formulations of the mixture and to identify optimal proportions for each of the ingredients, little research has been done concerning their I-optimal desi...

  20. Optimizing queries in distributed systems

    Directory of Open Access Journals (Sweden)

    Ion LUNGU

    2006-01-01

    Full Text Available This research presents the main elements of query optimizations in distributed systems. First, data architecture according with system level architecture in a distributed environment is presented. Then the architecture of a distributed database management system (DDBMS is described on conceptual level followed by the presentation of the distributed query execution steps on these information systems. The research ends with presentation of some aspects of distributed database query optimization and strategies used for that.