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Sample records for linear pde approach

  1. A "Reverse-Schur" Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design.

    Science.gov (United States)

    Bardhan, Jaydeep P; Altman, Michael D; Tidor, B; White, Jacob K

    2009-01-01

    We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule's electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts-in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method.

  2. A “Reverse-Schur” Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design

    Science.gov (United States)

    Bardhan, Jaydeep P.; Altman, Michael D.

    2009-01-01

    We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule’s electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts–in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method. PMID:23055839

  3. Using system theory and energy methods to prove existence of non-linear PDE's

    NARCIS (Netherlands)

    Zwart, H.J.

    2015-01-01

    In this discussion paper we present an idea of combining techniques known from systems theory with energy estimates to show existence for a class of non-linear partial differential equations (PDE's). At the end of the paper a list of research questions with possible approaches is given.

  4. Boundary Control of Linear Uncertain 1-D Parabolic PDE Using Approximate Dynamic Programming.

    Science.gov (United States)

    Talaei, Behzad; Jagannathan, Sarangapani; Singler, John

    2018-04-01

    This paper develops a near optimal boundary control method for distributed parameter systems governed by uncertain linear 1-D parabolic partial differential equations (PDE) by using approximate dynamic programming. A quadratic surface integral is proposed to express the optimal cost functional for the infinite-dimensional state space. Accordingly, the Hamilton-Jacobi-Bellman (HJB) equation is formulated in the infinite-dimensional domain without using any model reduction. Subsequently, a neural network identifier is developed to estimate the unknown spatially varying coefficient in PDE dynamics. Novel tuning law is proposed to guarantee the boundedness of identifier approximation error in the PDE domain. A radial basis network (RBN) is subsequently proposed to generate an approximate solution for the optimal surface kernel function online. The tuning law for near optimal RBN weights is created, such that the HJB equation error is minimized while the dynamics are identified and closed-loop system remains stable. Ultimate boundedness (UB) of the closed-loop system is verified by using the Lyapunov theory. The performance of the proposed controller is successfully confirmed by simulation on an unstable diffusion-reaction process.

  5. Biomolecular surface construction by PDE transform.

    Science.gov (United States)

    Zheng, Qiong; Yang, Siyang; Wei, Guo-Wei

    2012-03-01

    This work proposes a new framework for the surface generation based on the partial differential equation (PDE) transform. The PDE transform has recently been introduced as a general approach for the mode decomposition of images, signals, and data. It relies on the use of arbitrarily high-order PDEs to achieve the time-frequency localization, control the spectral distribution, and regulate the spatial resolution. The present work provides a new variational derivation of high-order PDE transforms. The fast Fourier transform is utilized to accomplish the PDE transform so as to avoid stringent stability constraints in solving high-order PDEs. As a consequence, the time integration of high-order PDEs can be done efficiently with the fast Fourier transform. The present approach is validated with a variety of test examples in two-dimensional and three-dimensional settings. We explore the impact of the PDE transform parameters, such as the PDE order and propagation time, on the quality of resulting surfaces. Additionally, we utilize a set of 10 proteins to compare the computational efficiency of the present surface generation method and a standard approach in Cartesian meshes. Moreover, we analyze the present method by examining some benchmark indicators of biomolecular surface, that is, surface area, surface-enclosed volume, solvation free energy, and surface electrostatic potential. A test set of 13 protein molecules is used in the present investigation. The electrostatic analysis is carried out via the Poisson-Boltzmann equation model. To further demonstrate the utility of the present PDE transform-based surface method, we solve the Poisson-Nernst-Planck equations with a PDE transform surface of a protein. Second-order convergence is observed for the electrostatic potential and concentrations. Finally, to test the capability and efficiency of the present PDE transform-based surface generation method, we apply it to the construction of an excessively large biomolecule, a

  6. PDE9A, PDE10A, and PDE11A expression in rat trigeminovascular pain signalling system

    DEFF Research Database (Denmark)

    Kruse, Lars S; Møller, Morten; Tibaek, Maiken

    2009-01-01

    as neocortex and cerebellar cortex. Real-time PCR and Western blotting showed that PDE9A, PDE10A and PDE11A are expressed in components of the rat trigeminovascular pain signalling system including middle cerebral artery, basilar artery, meninges, trigeminal ganglion and spinal trigeminal nucleus. Aorta...... and mesenteric artery as well as cerebral neocortex and cerebellar cortex also showed expression of PDE9A, PDE10A and PDE11A. Immunohistochemistry revealed that PDE9A, PDE10A and PDE11A are localised in the cytosol of nerve cell bodies of the trigeminal ganglion. We here present, for the first time...

  7. Exploring pyrazolo[3,4-d]pyrimidine phosphodiesterase 1 (PDE1) inhibitors: a predictive approach combining comparative validated multiple molecular modelling techniques.

    Science.gov (United States)

    Amin, Sk Abdul; Bhargava, Sonam; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2018-02-01

    Phosphodiesterase 1 (PDE1) is a potential target for a number of neurodegenerative disorders such as Schizophrenia, Parkinson's and Alzheimer's diseases. A number of pyrazolo[3,4-d]pyrimidine PDE1 inhibitors were subjected to different molecular modelling techniques [such as regression-based quantitative structure-activity relationship (QSAR): multiple linear regression, support vector machine and artificial neural network; classification-based QSAR: Bayesian modelling and Recursive partitioning; Monte Carlo based QSAR; Open3DQSAR; pharmacophore mapping and molecular docking analyses] to get a detailed knowledge about the physicochemical and structural requirements for higher inhibitory activity. The planarity of the pyrimidinone ring plays an important role for PDE1 inhibition. The N-methylated function at the 5th position of the pyrazolo[3,4-d]pyrimidine core is required for interacting with the PDE1 enzyme. The cyclopentyl ring fused with the parent scaffold is necessary for PDE1 binding potency. The phenylamino substitution at 3rd position is crucial for PDE1 inhibition. The N2-substitution at the pyrazole moiety is important for PDE1 inhibition compared to the N1-substituted analogues. Moreover, the p-substituted benzyl side chain at N2-position helps to enhance the PDE1 inhibitory profile. Depending on these observations, some new molecules are predicted that may possess better PDE1 inhibition.

  8. Stopping test of iterative methods for solving PDE

    International Nuclear Information System (INIS)

    Wang Bangrong

    1991-01-01

    In order to assure the accuracy of the numerical solution of the iterative method for solving PDE (partial differential equation), the stopping test is very important. If the coefficient matrix of the system of linear algebraic equations is strictly diagonal dominant or irreducible weakly diagonal dominant, the stopping test formulas of the iterative method for solving PDE is proposed. Several numerical examples are given to illustrate the applications of the stopping test formulas

  9. Pricing index-based catastrophe bonds: Part 1: Formulation and discretization issues using a numerical PDE approach

    Science.gov (United States)

    Unger, André J. A.

    2010-02-01

    This work is the first installment in a two-part series, and focuses on the development of a numerical PDE approach to price components of a Bermudan-style callable catastrophe (CAT) bond. The bond is based on two underlying stochastic variables; the PCS index which posts quarterly estimates of industry-wide hurricane losses as well as a single-factor CIR interest rate model for the three-month LIBOR. The aggregate PCS index is analogous to losses claimed under traditional reinsurance in that it is used to specify a reinsurance layer. The proposed CAT bond model contains a Bermudan-style call feature designed to allow the reinsurer to minimize their interest rate risk exposure on making substantial fixed coupon payments using capital from the reinsurance premium. Numerical PDE methods are the fundamental strategy for pricing early-exercise constraints, such as the Bermudan-style call feature, into contingent claim models. Therefore, the objective and unique contribution of this first installment in the two-part series is to develop a formulation and discretization strategy for the proposed CAT bond model utilizing a numerical PDE approach. Object-oriented code design is fundamental to the numerical methods used to aggregate the PCS index, and implement the call feature. Therefore, object-oriented design issues that relate specifically to the development of a numerical PDE approach for the component of the proposed CAT bond model that depends on the PCS index and LIBOR are described here. Formulation, numerical methods and code design issues that relate to aggregating the PCS index and introducing the call option are the subject of the companion paper.

  10. A penalty method for PDE-constrained optimization in inverse problems

    International Nuclear Information System (INIS)

    Leeuwen, T van; Herrmann, F J

    2016-01-01

    Many inverse and parameter estimation problems can be written as PDE-constrained optimization problems. The goal is to infer the parameters, typically coefficients of the PDE, from partial measurements of the solutions of the PDE for several right-hand sides. Such PDE-constrained problems can be solved by finding a stationary point of the Lagrangian, which entails simultaneously updating the parameters and the (adjoint) state variables. For large-scale problems, such an all-at-once approach is not feasible as it requires storing all the state variables. In this case one usually resorts to a reduced approach where the constraints are explicitly eliminated (at each iteration) by solving the PDEs. These two approaches, and variations thereof, are the main workhorses for solving PDE-constrained optimization problems arising from inverse problems. In this paper, we present an alternative method that aims to combine the advantages of both approaches. Our method is based on a quadratic penalty formulation of the constrained optimization problem. By eliminating the state variable, we develop an efficient algorithm that has roughly the same computational complexity as the conventional reduced approach while exploiting a larger search space. Numerical results show that this method indeed reduces some of the nonlinearity of the problem and is less sensitive to the initial iterate. (paper)

  11. Estimating the magnitude of near-membrane PDE4 activity in living cells.

    Science.gov (United States)

    Xin, Wenkuan; Feinstein, Wei P; Britain, Andrea L; Ochoa, Cristhiaan D; Zhu, Bing; Richter, Wito; Leavesley, Silas J; Rich, Thomas C

    2015-09-15

    Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. Copyright © 2015 the American Physiological Society.

  12. A boundary PDE feedback control approach for the stabilization of mortgage price dynamics

    Science.gov (United States)

    Rigatos, G.; Siano, P.; Sarno, D.

    2017-11-01

    Several transactions taking place in financial markets are dependent on the pricing of mortgages (loans for the purchase of residences, land or farms). In this article, a method for stabilization of mortgage price dynamics is developed. It is considered that mortgage prices follow a PDE model which is equivalent to a multi-asset Black-Scholes PDE. Actually it is a diffusion process evolving in a 2D assets space, where the first asset is the house price and the second asset is the interest rate. By applying semi-discretization and a finite differences scheme this multi-asset PDE is transformed into a state-space model consisting of ordinary nonlinear differential equations. For the local subsystems, into which the mortgage PDE is decomposed, it becomes possible to apply boundary-based feedback control. The controller design proceeds by showing that the state-space model of the mortgage price PDE stands for a differentially flat system. Next, for each subsystem which is related to a nonlinear ODE, a virtual control input is computed, that can invert the subsystem's dynamics and can eliminate the subsystem's tracking error. From the last row of the state-space description, the control input (boundary condition) that is actually applied to the multi-factor mortgage price PDE system is found. This control input contains recursively all virtual control inputs which were computed for the individual ODE subsystems associated with the previous rows of the state-space equation. Thus, by tracing the rows of the state-space model backwards, at each iteration of the control algorithm, one can finally obtain the control input that should be applied to the mortgage price PDE system so as to assure that all its state variables will converge to the desirable setpoints. By showing the feasibility of such a control method it is also proven that through selected modification of the PDE boundary conditions the price of the mortgage can be made to converge and stabilize at specific

  13. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    Science.gov (United States)

    Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

    2016-01-01

    Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

  14. Multiscale Reaction-Diffusion Algorithms: PDE-Assisted Brownian Dynamics

    KAUST Repository

    Franz, Benjamin

    2013-06-19

    Two algorithms that combine Brownian dynami cs (BD) simulations with mean-field partial differential equations (PDEs) are presented. This PDE-assisted Brownian dynamics (PBD) methodology provides exact particle tracking data in parts of the domain, whilst making use of a mean-field reaction-diffusion PDE description elsewhere. The first PBD algorithm couples BD simulations with PDEs by randomly creating new particles close to the interface, which partitions the domain, and by reincorporating particles into the continuum PDE-description when they cross the interface. The second PBD algorithm introduces an overlap region, where both descriptions exist in parallel. It is shown that the overlap region is required to accurately compute variances using PBD simulations. Advantages of both PBD approaches are discussed and illustrative numerical examples are presented. © 2013 Society for Industrial and Applied Mathematics.

  15. Parallel PDE-Based Simulations Using the Common Component Architecture

    International Nuclear Information System (INIS)

    McInnes, Lois C.; Allan, Benjamin A.; Armstrong, Robert; Benson, Steven J.; Bernholdt, David E.; Dahlgren, Tamara L.; Diachin, Lori; Krishnan, Manoj Kumar; Kohl, James A.; Larson, J. Walter; Lefantzi, Sophia; Nieplocha, Jarek; Norris, Boyana; Parker, Steven G.; Ray, Jaideep; Zhou, Shujia

    2006-01-01

    The complexity of parallel PDE-based simulations continues to increase as multimodel, multiphysics, and multi-institutional projects become widespread. A goal of component based software engineering in such large-scale simulations is to help manage this complexity by enabling better interoperability among various codes that have been independently developed by different groups. The Common Component Architecture (CCA) Forum is defining a component architecture specification to address the challenges of high-performance scientific computing. In addition, several execution frameworks, supporting infrastructure, and general purpose components are being developed. Furthermore, this group is collaborating with others in the high-performance computing community to design suites of domain-specific component interface specifications and underlying implementations. This chapter discusses recent work on leveraging these CCA efforts in parallel PDE-based simulations involving accelerator design, climate modeling, combustion, and accidental fires and explosions. We explain how component technology helps to address the different challenges posed by each of these applications, and we highlight how component interfaces built on existing parallel toolkits facilitate the reuse of software for parallel mesh manipulation, discretization, linear algebra, integration, optimization, and parallel data redistribution. We also present performance data to demonstrate the suitability of this approach, and we discuss strategies for applying component technologies to both new and existing applications

  16. Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

    Science.gov (United States)

    Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

    2002-03-26

    Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

  17. Identification of cancer cytotoxic modulators of PDE3A by predictive chemogenomics

    Science.gov (United States)

    de Waal, Luc; Lewis, Timothy A.; Rees, Matthew G.; Tsherniak, Aviad; Wu, Xiaoyun; Choi, Peter S.; Gechijian, Lara; Hartigan, Christina; Faloon, Patrick W.; Hickey, Mark J.; Tolliday, Nicola; Carr, Steven A.; Clemons, Paul A.; Munoz, Benito; Wagner, Bridget K.; Shamji, Alykhan F.; Koehler, Angela N.; Schenone, Monica; Burgin, Alex B.; Schreiber, Stuart L.; Greulich, Heidi; Meyerson, Matthew

    2015-01-01

    High cancer death rates indicate the need for new anti-cancer therapeutic agents. Approaches to discover new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds by phenotypic compound library screening and target deconvolution by predictive chemogenomics. We found that sensitivity to 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, across 766 cancer cell lines correlates with expression of the phosphodiesterase 3A gene, PDE3A. Like DNMDP, a subset of known PDE3A inhibitors kill selected cancer cells while others do not. Furthermore, PDE3A depletion leads to DNMDP resistance. We demonstrated that DNMDP binding to PDE3A promotes an interaction between PDE3A and Schlafen 12 (SLFN12), suggesting a neomorphic activity. Co-expression of SLFN12 with PDE3A correlates with DNMDP sensitivity, while depletion of SLFN12 results in decreased DNMDP sensitivity. Our results implicate PDE3A modulators as candidate cancer therapeutic agents and demonstrate the power of predictive chemogenomics in small-molecule discovery. PMID:26656089

  18. Adaptive wavelet collocation methods for initial value boundary problems of nonlinear PDE's

    Science.gov (United States)

    Cai, Wei; Wang, Jian-Zhong

    1993-01-01

    We have designed a cubic spline wavelet decomposition for the Sobolev space H(sup 2)(sub 0)(I) where I is a bounded interval. Based on a special 'point-wise orthogonality' of the wavelet basis functions, a fast Discrete Wavelet Transform (DWT) is constructed. This DWT transform will map discrete samples of a function to its wavelet expansion coefficients in O(N log N) operations. Using this transform, we propose a collocation method for the initial value boundary problem of nonlinear PDE's. Then, we test the efficiency of the DWT transform and apply the collocation method to solve linear and nonlinear PDE's.

  19. Co-possession of phosphodiesterase type-5 inhibitors (PDE5-I) with nitrates.

    Science.gov (United States)

    Chang, Li-Ling; Ma, Mark; Allmen, Heather von; Henderson, Scott C; Harper, Kristine; Hornbuckle, Kenneth

    2010-06-01

    Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group. Secondarily, examine the percentage of co-possession of PDE5-Is and nitrates where the products were dispensed on the same day or written by the same prescriber. Male patients aged 18+ years filling PDE5-I prescriptions between December 2003 and March 2006 were identified using a U.S. longitudinal prescription database (IMS Health LRx). Similar patients not dispensed a PDE5-I during this period were matched to the tadalafil-dispensed cohort using a propensity score approach. Co-possession, as a proxy for concurrent use, was defined as an overlap in time on therapy for a PDE5-I and nitrate and was compared for the three PDE5-Is and for tadalafil to the matched control group. Among 601,063 tadalafil patients, 3.31% were dispensed a nitrate during the study period, compared to 6.18% in control patients (n = 601,063). When co-possessed prescriptions were defined by overlapping exposure periods, the proportion of PDE5-I patients with co-possessed nitrates ranged from 1.44% (tadalafil) to 1.72% (vardenafil) and 2.13% (sildenafil). Co-possession percentages of PDE5-I prescriptions were 0.83% for tadalafil and 1.07% for sildenafil and vardenafil. The majority (54.29%) of co-possessed PDE5-I and nitrate prescriptions had the nitrate dispensed prior to the PDE5-I prescription identified in the study cohort. Keeping in mind the limitations of observational studies, these results suggest that co-dispensing of nitrates and PDE5-Is is low. Compared to control patients, the proportion of nitrate co-possession was lowest for patients filling tadalafil. Tadalafil patients also had the lowest co-possessed proportion among the three PDE5-I cohorts. While the majority of co-possessed drug pairs were prescribed by different providers, the highest percentage of co-prescribing from the same

  20. PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

    Science.gov (United States)

    Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

    2013-01-01

    Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of

  1. Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted

    2016-08-24

    Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The

  2. Optimal traffic control in highway transportation networks using linear programming

    KAUST Repository

    Li, Yanning; Canepa, Edward S.; Claudel, Christian G.

    2014-01-01

    of the Hamilton-Jacobi PDE, the problem of controlling the state of the system on a network link in a finite horizon can be posed as a Linear Program. Assuming all intersections in the network are controllable, we show that the optimization approach can

  3. Research on odor interaction between aldehyde compounds via a partial differential equation (PDE) model.

    Science.gov (United States)

    Yan, Luchun; Liu, Jiemin; Qu, Chen; Gu, Xingye; Zhao, Xia

    2015-01-28

    In order to explore the odor interaction of binary odor mixtures, a series of odor intensity evaluation tests were performed using both individual components and binary mixtures of aldehydes. Based on the linear relation between the logarithm of odor activity value and odor intensity of individual substances, the relationship between concentrations of individual constituents and their joint odor intensity was investigated by employing a partial differential equation (PDE) model. The obtained results showed that the binary odor interaction was mainly influenced by the mixing ratio of two constituents, but not the concentration level of an odor sample. Besides, an extended PDE model was also proposed on the basis of the above experiments. Through a series of odor intensity matching tests for several different binary odor mixtures, the extended PDE model was proved effective at odor intensity prediction. Furthermore, odorants of the same chemical group and similar odor type exhibited similar characteristics in the binary odor interaction. The overall results suggested that the PDE model is a more interpretable way of demonstrating the odor interactions of binary odor mixtures.

  4. PDE-Foam - a probability-density estimation method using self-adapting phase-space binning

    CERN Document Server

    Dannheim, Dominik; Voigt, Alexander; Grahn, Karl-Johan; Speckmayer, Peter

    2009-01-01

    Probability-Density Estimation (PDE) is a multivariate discrimination technique based on sampling signal and background densities defined by event samples from data or Monte-Carlo (MC) simulations in a multi-dimensional phase space. To efficiently use large event samples to estimate the probability density, a binary search tree (range searching) is used in the PDE-RS implementation. It is a generalisation of standard likelihood methods and a powerful classification tool for problems with highly non-linearly correlated observables. In this paper, we present an innovative improvement of the PDE method that uses a self-adapting binning method to divide the multi-dimensional phase space in a finite number of hyper-rectangles (cells). The binning algorithm adjusts the size and position of a predefined number of cells inside the multidimensional phase space, minimizing the variance of the signal and background densities inside the cells. The binned density information is stored in binary trees, allowing for a very ...

  5. The emperor's new clothes: PDE5 and the heart.

    Directory of Open Access Journals (Sweden)

    Chantal V Degen

    Full Text Available Phosphodiesterase-5 (PDE5 is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP activates protein kinase G (PKG, which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction, dog (control and HFpEF as well as human (healthy and failing heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design.

  6. Commutator identities on associative algebras and integrability of nonlinear pde's

    OpenAIRE

    Pogrebkov, A. K.

    2007-01-01

    It is shown that commutator identities on associative algebras generate solutions of linearized integrable equations. Next, a special kind of the dressing procedure is suggested that in a special class of integral operators enables to associate to such commutator identity both nonlinear equation and its Lax pair. Thus problem of construction of new integrable pde's reduces to construction of commutator identities on associative algebras.

  7. Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.

    Science.gov (United States)

    Viringipurampeer, I A; Shan, X; Gregory-Evans, K; Zhang, J P; Mohammadi, Z; Gregory-Evans, C Y

    2014-05-01

    Achromatopsia is a progressive autosomal recessive retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss. In most cases, mutations have been identified in CNGA3, CNGB3, GNAT2, PDE6C or PDE6H genes. Owing to this genetic heterogeneity, mutation-independent therapeutic schemes aimed at preventing cone cell death are very attractive treatment strategies. In pde6c(w59) mutant zebrafish, cone photoreceptors expressed high levels of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3) kinases, key regulators of necroptotic cell death. In contrast, rod photoreceptor cells were alternatively immunopositive for caspase-3 indicating activation of caspase-dependent apoptosis in these cells. Morpholino gene knockdown of rip3 in pde6c(w59) embryos rescued the dying cone photoreceptors by inhibiting the formation of reactive oxygen species and by inhibiting second-order neuron remodelling in the inner retina. In rip3 morphant larvae, visual function was restored in the cones by upregulation of the rod phosphodiesterase genes (pde6a and pde6b), compensating for the lack of cone pde6c suggesting that cones are able to adapt to their local environment. Furthermore, we demonstrated through pharmacological inhibition of RIP1 and RIP3 activity that cone cell death was also delayed. Collectively, these results demonstrate that the underlying mechanism of cone cell death in the pde6c(w59) mutant retina is through necroptosis, whereas rod photoreceptor bystander death occurs through a caspase-dependent mechanism. This suggests that targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. As bystander cell death is an important feature of many retinal diseases, combinatorial approaches targeting different cell death pathways may evolve as an important general principle in treatment.

  8. Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

    Science.gov (United States)

    Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

    2017-06-01

    Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

  9. In vitro differentiation of human monocytes to macrophages: change of PDE profile and its relationship to suppression of tumour necrosis factor-α release by PDE inhibitors

    Science.gov (United States)

    Gantner, Florian; Kupferschmidt, Rochus; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

    1997-01-01

    During in vitro culture in 10% human AB serum, human peripheral blood monocytes acquire a macrophage-like phenotype. The underlying differentiation was characterized by increased activities of the macrophage marker enzymes unspecific esterase (NaF-insensitive form) and acid phosphatase, as well as by a down-regulation in surface CD14 expression. In parallel, a dramatic change in the phosphodiesterase (PDE) profile became evident within a few days that strongly resembled that previously described for human alveolar macrophages. Whereas PDE1 and PDE3 activities were augmented, PDE4 activity, which represented the major cyclic AMP-hydrolysing activity of peripheral blood monocytes, rapidly declined. Monocytes and monocyte-derived macrophages responded to lipopolysaccharide (LPS) with the release of tumour necrosis factor-α (TNF). In line with the change in CD14 expression, the EC50 value of LPS for induction of TNF release increased from approximately 0.1 ng ml−1 in peripheral blood monocytes to about 2 ng ml−1 in macrophages. Both populations of cells were equally susceptible towards inhibition of TNF release by cyclic AMP elevating agents such as dibutyryl cyclic AMP, prostaglandin E2 (PGE2) or forskolin, which all led to a complete abrogation of TNF production in a concentration-dependent manner and which were more efficient than the glucocorticoid dexamethasone. In monocytes, PDE4 selective inhibitors (rolipram, RP73401) suppressed TNF formation by 80%, whereas motapizone, a PDE3 selective compound, exerted a comparatively weak effect (10–15% inhibition). Combined use of PDE3 plus PDE4 inhibitors resulted in an additive effect and fully abrogated LPS-induced TNF release as did the mixed PDE3/4 inhibitor tolafentrine. In monocyte-derived macrophages, neither PDE3- nor PDE4-selective drugs markedly affected TNF generation when used alone (<15% inhibition), whereas in combination, they led to a maximal inhibition of TNF formation by about 40–50

  10. Optimal traffic control in highway transportation networks using linear programming

    KAUST Repository

    Li, Yanning

    2014-06-01

    This article presents a framework for the optimal control of boundary flows on transportation networks. The state of the system is modeled by a first order scalar conservation law (Lighthill-Whitham-Richards PDE). Based on an equivalent formulation of the Hamilton-Jacobi PDE, the problem of controlling the state of the system on a network link in a finite horizon can be posed as a Linear Program. Assuming all intersections in the network are controllable, we show that the optimization approach can be extended to an arbitrary transportation network, preserving linear constraints. Unlike previously investigated transportation network control schemes, this framework leverages the intrinsic properties of the Halmilton-Jacobi equation, and does not require any discretization or boolean variables on the link. Hence this framework is very computational efficient and provides the globally optimal solution. The feasibility of this framework is illustrated by an on-ramp metering control example.

  11. Effect of PVA and PDE on selected structural characteristics of extrusion-cooked starch foams

    Directory of Open Access Journals (Sweden)

    Maciej Combrzyński

    2018-03-01

    Full Text Available Abstract The aim of this work was to determine selected physical properties of biodegradable thermoplastic starch (TPS filling foams manufactured by extrusion-cooking technique from different combinations of potato starch and two additives: poly(vinyl alcohol PVA and Plastronfoam PDE. Foams were processed with seven starch/additives combinations at two different extruder-cooker’s screw rotational speeds. The densities of starch foams depended significantly on the additive type and content. The linear relationship between the Young modulus and the ultimate compression force and apparent density was found. The foams processed with the addition of PVA had low density, porosity and lower values of the Young modulus than the foams prepared with PDE.

  12. Parallels between control PDE's (Partial Differential Equations) and systems of ODE's (Ordinary Differential Equations)

    Science.gov (United States)

    Hunt, L. R.; Villarreal, Ramiro

    1987-01-01

    System theorists understand that the same mathematical objects which determine controllability for nonlinear control systems of ordinary differential equations (ODEs) also determine hypoellipticity for linear partial differentail equations (PDEs). Moreover, almost any study of ODE systems begins with linear systems. It is remarkable that Hormander's paper on hypoellipticity of second order linear p.d.e.'s starts with equations due to Kolmogorov, which are shown to be analogous to the linear PDEs. Eigenvalue placement by state feedback for a controllable linear system can be paralleled for a Kolmogorov equation if an appropriate type of feedback is introduced. Results concerning transformations of nonlinear systems to linear systems are similar to results for transforming a linear PDE to a Kolmogorov equation.

  13. PDE5 Inhibitors As Potential Tools In The Treatment Of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Sabrina eNoel

    2012-09-01

    Full Text Available Despite great advances in the understanding of the genetics and pathophysiology of cystic fibrosis (CF, there is still no cure for the disease. Using phosphodiesterase type 5 (PDE5 inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and corrected deficient chloride transport activity. Studies using PDE5 inhibitors in mice homozygous for the clinically relevant F508del mutation have been conducted with the aim of restoring F508del-CFTR protein function. We demonstrated, by measuring transepithelial nasal potential difference in F508del mice following intraperitoneal injection of sildenafil, vardenafil or taladafil at clinical doses are able to restore the decreased CFTR-dependent chloride transport across the nasal mucosa. Moreover, vardenafil, but not sildenafil, stimulates chloride transport through the normal CFTR protein. We developed a specific nebulizer setup for mice, with which we demonstrated, through a single inhalation of PDE5 inhibitors, local activation of CFTR protein in CF. Significant potential advantages of inhalation drug therapy over oral or intravenous routes include rapid onset of pharmacological action, reduced systemic secondary effects and reduced effective drug doses compared to the drug delivered orally; this underlines the relevance and impact of our work for translational science. More recently, we analyzed the bronchoalveolar lavage of CF and wild-type mice for cell infiltrates and expression of pro-inflammatory cytokines and chemokines; we found that the CFTR activating effect of vardenafil, selected as a representative long-lasting PDE5 inhibitor, breaks the vicious circle of lung inflammation which plays a major role in morbi-mortality in CF. Our data highlight the potential use of PDE5 inhibitors in CF. Therapeutic approaches using clinically approved PDE5 inhibitors to address F508del-CFTR defects could speed up the development of new therapies for CF.

  14. Novel selective PDE type 1 inhibitors cause vasodilatation and lower blood pressure in rats

    DEFF Research Database (Denmark)

    Laursen, Morten; Beck, Lilliana; Kehler, Jan

    2017-01-01

    BACKGROUND AND PURPOSE: The PDE enzymes (PDE1-11) hydrolyse and thus inactivate cyclic nucleotides and are important in the regulation of the cardiovascular system. Here,we have investigated the effects on the cardiovascular system, of two novel selective PDE1 inhibitors, Lu AF41228 and Lu AF58027...... and Lu AF58027 inhibited PDE1A, PDE1B and PDE1C enzyme activity, while micromolar concentrations were required to observe inhibitory effects at other PDEs. RT-PCR revealed expression of PDE1A, PDE1B and PDE1C in rat brain, heart and aorta, but only PDE1A and PDE1B in mesenteric arteries. In rat isolated...... and Lu AF58027 dose-dependently lowered mean BP and increased heart rate. In conscious rats with telemetric pressure transducers, repeated dosing with Lu AF41228 lowered mean arterial BP 10-15 mmHg and increased heart rate. CONCLUSIONS AND IMPLICATIONS: These novel PDE1 inhibitors induce vasodilation...

  15. Mesh dependence in PDE-constrained optimisation an application in tidal turbine array layouts

    CERN Document Server

    Schwedes, Tobias; Funke, Simon W; Piggott, Matthew D

    2017-01-01

    This book provides an introduction to PDE-constrained optimisation using finite elements and the adjoint approach. The practical impact of the mathematical insights presented here are demonstrated using the realistic scenario of the optimal placement of marine power turbines, thereby illustrating the real-world relevance of best-practice Hilbert space aware approaches to PDE-constrained optimisation problems. Many optimisation problems that arise in a real-world context are constrained by partial differential equations (PDEs). That is, the system whose configuration is to be optimised follows physical laws given by PDEs. This book describes general Hilbert space formulations of optimisation algorithms, thereby facilitating optimisations whose controls are functions of space. It demonstrates the importance of methods that respect the Hilbert space structure of the problem by analysing the mathematical drawbacks of failing to do so. The approaches considered are illustrated using the optimisation problem arisin...

  16. Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2000-12-29

    Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

  17. PDE1A inhibition elicits cGMP-dependent relaxation of rat mesenteric arteries

    DEFF Research Database (Denmark)

    Khammy, Makhala Michell; Dalsgaard, Thomas; Larsen, Peter Hjorringgaard

    2017-01-01

    (EC50 = 32 nM). Inhibition of NOS with L-NAME, soluble GC with ODQ, or PKG with Rp-8-Br-PET-cGMP all attenuated PDE1 inhibition-induced relaxation, whereas PKA inhibition with H89 had no effect. CONCLUSION AND IMPLICATIONS: Pde1a was the dominant PDE1 isoform present in VSMC and relaxation mediated...... by PDE1A-inhibition was predominantly driven by enhanced cGMP signalling. These results imply that isoform-selective PDE1 inhibitors are powerful investigative tools allowing examination of physiological and pathological roles of PDE1 isoforms....

  18. PDE7B is a novel, prognostically significant mediator of glioblastoma growth whose expression is regulated by endothelial cells.

    Directory of Open Access Journals (Sweden)

    Michael D Brooks

    Full Text Available Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM cells and endothelial cells (ECs establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM.

  19. A PDE Pricing Framework for Cross-Currency Interest Rate Derivatives with Target Redemption Features

    Science.gov (United States)

    Christara, Christina C.; Minh Dang, Duy; Jackson, Kenneth R.; Lakhany, Asif

    2010-09-01

    We propose a general framework for efficient pricing via a partial differential equation (PDE) approach for exotic cross-currency interest rate (IR) derivatives, with strong emphasis on long-dated foreign exchange (FX) IR hybrids, namely Power Reverse Dual Currency (PRDC) swaps with a FX Target Redemption (FX-TARN) provision. The FX-TARN provision provides a cap on the FX-linked PRDC coupon amounts, and once the accumulated coupon amount reaches this cap, the underlying PRDC swap terminates. Our PDE pricing framework is based on an auxiliary state variable to keep track of the total accumulated PRDC coupon amount. Finite differences on uniform grids and the Alternating Direction Implicit (ADI) method are used for the spatial and time discretizations, respectively, of the model-dependent PDE corresponding to each discretized value of the auxiliary variable. Numerical examples illustrating the convergence properties of the numerical methods are provided.

  20. Is PDE4 too difficult a drug target?

    Science.gov (United States)

    Higgs, Gerry

    2010-05-01

    The search for selective inhibitors of PDE4 as novel anti-inflammatory drugs has continued for more than 30 years. Although several compounds have demonstrated therapeutic effects in diseases such as asthma, COPD, atopic dermatitis and psoriasis, none have reached the market. A persistent challenge in the development of PDE4 inhibitors has been drug-induced gastrointestinal adverse effects, such as nausea. However, extensive clinical trials with well-tolerated doses of roflumilast (Daxas; Nycomed/Mitsubishi Tanabe Pharma Corp/Forest Laboratories Inc) in COPD, a disease that is generally unresponsive to existing therapies, have demonstrated significant therapeutic improvements. In addition, GlaxoSmithKline plc is developing 256066, an inhaled formulation of a PDE4 inhibitor that has demonstrated efficacy in trials in asthma, and apremilast from Celgene Corp has been reported to be effective for the treatment of psoriasis. Despite the challenges and complications that have been encountered during the development of PDE4 inhibitors, these drugs may provide a genuinely novel class of anti-inflammatory agents, and there are several compounds in development that could fulfill that promise.

  1. Numerical Methods for Pricing American Options with Time-Fractional PDE Models

    Directory of Open Access Journals (Sweden)

    Zhiqiang Zhou

    2016-01-01

    Full Text Available In this paper we develop a Laplace transform method and a finite difference method for solving American option pricing problem when the change of the option price with time is considered as a fractal transmission system. In this scenario, the option price is governed by a time-fractional partial differential equation (PDE with free boundary. The Laplace transform method is applied to the time-fractional PDE. It then leads to a nonlinear equation for the free boundary (i.e., optimal early exercise boundary function in Laplace space. After numerically finding the solution of the nonlinear equation, the Laplace inversion is used to transform the approximate early exercise boundary into the time space. Finally the approximate price of the American option is obtained. A boundary-searching finite difference method is also proposed to solve the free-boundary time-fractional PDEs for pricing the American options. Numerical examples are carried out to compare the Laplace approach with the finite difference method and it is confirmed that the former approach is much faster than the latter one.

  2. A novel algebraic procedure for solving non-linear evolution equations of higher order

    International Nuclear Information System (INIS)

    Huber, Alfred

    2007-01-01

    We report here a systematic approach that can easily be used for solving non-linear partial differential equations (nPDE), especially of higher order. We restrict the analysis to the so called evolution equations describing any wave propagation. The proposed new algebraic approach leads us to traveling wave solutions and moreover, new class of solution can be obtained. The crucial step of our method is the basic assumption that the solutions satisfy an ordinary differential equation (ODE) of first order that can be easily integrated. The validity and reliability of the method is tested by its application to some non-linear evolution equations. The important aspect of this paper however is the fact that we are able to calculate distinctive class of solutions which cannot be found in the current literature. In other words, using this new algebraic method the solution manifold is augmented to new class of solution functions. Simultaneously we would like to stress the necessity of such sophisticated methods since a general theory of nPDE does not exist. Otherwise, for practical use the algebraic construction of new class of solutions is of fundamental interest

  3. Selective Extraction of Entangled Textures via Adaptive PDE Transform

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2012-01-01

    Full Text Available Texture and feature extraction is an important research area with a wide range of applications in science and technology. Selective extraction of entangled textures is a challenging task due to spatial entanglement, orientation mixing, and high-frequency overlapping. The partial differential equation (PDE transform is an efficient method for functional mode decomposition. The present work introduces adaptive PDE transform algorithm to appropriately threshold the statistical variance of the local variation of functional modes. The proposed adaptive PDE transform is applied to the selective extraction of entangled textures. Successful separations of human face, clothes, background, natural landscape, text, forest, camouflaged sniper and neuron skeletons have validated the proposed method.

  4. New PDE-based methods for image enhancement using SOM and Bayesian inference in various discretization schemes

    International Nuclear Information System (INIS)

    Karras, D A; Mertzios, G B

    2009-01-01

    A novel approach is presented in this paper for improving anisotropic diffusion PDE models, based on the Perona–Malik equation. A solution is proposed from an engineering perspective to adaptively estimate the parameters of the regularizing function in this equation. The goal of such a new adaptive diffusion scheme is to better preserve edges when the anisotropic diffusion PDE models are applied to image enhancement tasks. The proposed adaptive parameter estimation in the anisotropic diffusion PDE model involves self-organizing maps and Bayesian inference to define edge probabilities accurately. The proposed modifications attempt to capture not only simple edges but also difficult textural edges and incorporate their probability in the anisotropic diffusion model. In the context of the application of PDE models to image processing such adaptive schemes are closely related to the discrete image representation problem and the investigation of more suitable discretization algorithms using constraints derived from image processing theory. The proposed adaptive anisotropic diffusion model illustrates these concepts when it is numerically approximated by various discretization schemes in a database of magnetic resonance images (MRI), where it is shown to be efficient in image filtering and restoration applications

  5. DISC1, PDE4B, and NDE1 at the centrosome and synapse

    International Nuclear Information System (INIS)

    Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz; Chubb, Jennifer E.; Carlyle, Becky C.; Christie, Sheila; Claessens, Antoine; Porteous, David J.; Millar, J. Kirsty

    2008-01-01

    Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

  6. Convergence of hybrid methods for solving non-linear partial ...

    African Journals Online (AJOL)

    This paper is concerned with the numerical solution and convergence analysis of non-linear partial differential equations using a hybrid method. The solution technique involves discretizing the non-linear system of PDE to obtain a corresponding non-linear system of algebraic difference equations to be solved at each time ...

  7. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  8. A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

    Science.gov (United States)

    Granovsky, A E; Artemyev, N O

    2001-11-06

    In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

  9. New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is).

    Science.gov (United States)

    Ribaudo, Giovanni; Pagano, Mario Angelo; Bova, Sergio; Zagotto, Giuseppe

    2016-01-01

    Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). In addition to this, sildenafil and tadalafil, have also been approved for the treatment of pulmonary arterial hypertension. Due to its expression and localization in many tissues, PDE5 and its regulation has been reported to be involved in several other diseases. We aim to provide an updated overview of the emerging therapeutic applications of PDE5-Is besides ED, taking into account the latest ongoing research reports. We searched online databases (Pubmed, Reaxys, Scopus) to lay the bases for an accurate, quality criteria-based literature update. We focused our attention on most recent research reports, in particular when supported by pre-clinical and clinical data. The regulation of PDE5 may influence pathological conditions such as, among the others, heart failure, cystic fibrosis, cancer, CNS-related diseases, diabetes and dysfunctions affecting male urinary/reproductive system. Sildenafil, vardenafil, tadalafil and the other chemical entities considered PDE5-Is showed overall positive results and significant improvements in the studied disease, thus some discordant results, in particular when comparing pre-clinical and clinical data, have to be pointed out, suggesting that further insights are needed especially to assess the exact molecular pathway underlying.

  10. Collocation methods for uncertainty quanti cation in PDE models with random data

    KAUST Repository

    Nobile, Fabio

    2014-01-06

    In this talk we consider Partial Differential Equations (PDEs) whose input data are modeled as random fields to account for their intrinsic variability or our lack of knowledge. After parametrizing the input random fields by finitely many independent random variables, we exploit the high regularity of the solution of the PDE as a function of the input random variables and consider sparse polynomial approximations in probability (Polynomial Chaos expansion) by collocation methods. We first address interpolatory approximations where the PDE is solved on a sparse grid of Gauss points in the probability space and the solutions thus obtained interpolated by multivariate polynomials. We present recent results on optimized sparse grids in which the selection of points is based on a knapsack approach and relies on sharp estimates of the decay of the coefficients of the polynomial chaos expansion of the solution. Secondly, we consider regression approaches where the PDE is evaluated on randomly chosen points in the probability space and a polynomial approximation constructed by the least square method. We present recent theoretical results on the stability and optimality of the approximation under suitable conditions between the number of sampling points and the dimension of the polynomial space. In particular, we show that for uniform random variables, the number of sampling point has to scale quadratically with the dimension of the polynomial space to maintain the stability and optimality of the approximation. Numerical results show that such condition is sharp in the monovariate case but seems to be over-constraining in higher dimensions. The regression technique seems therefore to be attractive in higher dimensions.

  11. Simulation of Stochastic Processes by Coupled ODE-PDE

    Science.gov (United States)

    Zak, Michail

    2008-01-01

    A document discusses the emergence of randomness in solutions of coupled, fully deterministic ODE-PDE (ordinary differential equations-partial differential equations) due to failure of the Lipschitz condition as a new phenomenon. It is possible to exploit the special properties of ordinary differential equations (represented by an arbitrarily chosen, dynamical system) coupled with the corresponding Liouville equations (used to describe the evolution of initial uncertainties in terms of joint probability distribution) in order to simulate stochastic processes with the proscribed probability distributions. The important advantage of the proposed approach is that the simulation does not require a random-number generator.

  12. Distribution of PDE8A in the nervous system of the Sprague-Dawley rat

    DEFF Research Database (Denmark)

    Kruse, Lars Schack; Møller, Morten; Kruuse, Christina

    2011-01-01

    in the brain of adult male Sprague-Dawley rats and in the trigeminal ganglion. PDE8A was confined to neuronal perikaryal cytoplasm and to processes extending from those perikarya. The neurons exhibiting PDE8A-immunoreactivity were widely distributed in the forebrain, brain stem, and cerebellum. Strongly...... immunoreactive neurons were located in the olfactory bulb, the septal area, zona incerta, and reticular nucleus of the thalamus. Less immunoreactivity was seen in the hippocampus and cerebral cortex. Intense staining was detected in both the substantia nigra and the sensory trigeminal nucleus. In cerebellum PDE8....... The localization of the cAMP degrading PDE8A may indicate a role for PDE8A in cAMP signaling related to pain transmission, motor function, cognition and olfaction....

  13. On the removal of boundary errors caused by Runge-Kutta integration of non-linear partial differential equations

    Science.gov (United States)

    Abarbanel, Saul; Gottlieb, David; Carpenter, Mark H.

    1994-01-01

    It has been previously shown that the temporal integration of hyperbolic partial differential equations (PDE's) may, because of boundary conditions, lead to deterioration of accuracy of the solution. A procedure for removal of this error in the linear case has been established previously. In the present paper we consider hyperbolic (PDE's) (linear and non-linear) whose boundary treatment is done via the SAT-procedure. A methodology is present for recovery of the full order of accuracy, and has been applied to the case of a 4th order explicit finite difference scheme.

  14. Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

    Science.gov (United States)

    Chen, Si; Knight, Walter E; Yan, Chen

    2018-04-23

    Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

  15. A General Symbolic PDE Solver Generator: Explicit Schemes

    Directory of Open Access Journals (Sweden)

    K. Sheshadri

    2003-01-01

    Full Text Available A symbolic solver generator to deal with a system of partial differential equations (PDEs in functions of an arbitrary number of variables is presented; it can also handle arbitrary domains (geometries of the independent variables. Given a system of PDEs, the solver generates a set of explicit finite-difference methods to any specified order, and a Fourier stability criterion for each method. For a method that is stable, an iteration function is generated symbolically using the PDE and its initial and boundary conditions. This iteration function is dynamically generated for every PDE problem, and its evaluation provides a solution to the PDE problem. A C++/Fortran 90 code for the iteration function is generated using the MathCode system, which results in a performance gain of the order of a thousand over Mathematica, the language that has been used to code the solver generator. Examples of stability criteria are presented that agree with known criteria; examples that demonstrate the generality of the solver and the speed enhancement of the generated C++ and Fortran 90 codes are also presented.

  16. Convergence acceleration for time-independent first-order PDE using optimal PNB-approximations

    Energy Technology Data Exchange (ETDEWEB)

    Holmgren, S.; Branden, H. [Uppsala Univ. (Sweden)

    1996-12-31

    We consider solving time-independent (steady-state) flow problems in 2D or 3D governed by hyperbolic or {open_quotes}almost hyperbolic{close_quotes} systems of partial differential equations (PDE). Examples of such PDE are the Euler and the Navier-Stokes equations. The PDE is discretized using a finite difference or finite volume scheme with arbitrary order of accuracy. If the matrix B describes the discretized differential operator and u denotes the approximate solution, the discrete problem is given by a large system of equations.

  17. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS.

    Science.gov (United States)

    Vignozzi, Linda; Gacci, Mauro; Cellai, Ilaria; Morelli, Annamaria; Maneschi, Elena; Comeglio, Paolo; Santi, Raffaella; Filippi, Sandra; Sebastianelli, Arcangelo; Nesi, Gabriella; Serni, Sergio; Carini, Marco; Maggi, Mario

    2013-09-01

    Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH)/low urinary tract symptoms (LUTS) are often comorbid. Chronic inflammation is one of the putative links between these diseases. Phosphodiesterase type 5 inhibitors (PDE5i) are recognized as an effective treatment of BPH-related LUTS. One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation. In this study we investigate whether PDE5i could blunt inflammation in the human prostate. Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 (IL-8, a surrogate marker of prostate inflammation) by human myofibroblast prostatic cells (hBPH) exposed to different inflammatory stimuli. We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a randomized, double bind, placebo controlled study aimed at investigating the efficacy of vardenafil (10 mg/day, for 12 weeks) on BPH/LUTS. In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors, including oxidized low-density lipoprotein, oxLDL, to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP. These effects were reverted by the PKG inhibitor KT5823, suggesting a cGMP/PKG-dependency. Treatment with tadalafil or vardenafil significantly suppressed oxLDL receptor (LOX-1) expression. Histological evaluation of anti-CD45 staining (CD45 score) in prostatectomy specimens of BPH patients showed a positive association with MetS severity. Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score. In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one. © 2013 Wiley Periodicals, Inc.

  18. Optimization with PDE constraints ESF networking program 'OPTPDE'

    CERN Document Server

    2014-01-01

    This book on PDE Constrained Optimization contains contributions on the mathematical analysis and numerical solution of constrained optimal control and optimization problems where a partial differential equation (PDE) or a system of PDEs appears as an essential part of the constraints. The appropriate treatment of such problems requires a fundamental understanding of the subtle interplay between optimization in function spaces and numerical discretization techniques and relies on advanced methodologies from the theory of PDEs and numerical analysis as well as scientific computing. The contributions reflect the work of the European Science Foundation Networking Programme ’Optimization with PDEs’ (OPTPDE).

  19. Fast solution of elliptic partial differential equations using linear combinations of plane waves.

    Science.gov (United States)

    Pérez-Jordá, José M

    2016-02-01

    Given an arbitrary elliptic partial differential equation (PDE), a procedure for obtaining its solution is proposed based on the method of Ritz: the solution is written as a linear combination of plane waves and the coefficients are obtained by variational minimization. The PDE to be solved is cast as a system of linear equations Ax=b, where the matrix A is not sparse, which prevents the straightforward application of standard iterative methods in order to solve it. This sparseness problem can be circumvented by means of a recursive bisection approach based on the fast Fourier transform, which makes it possible to implement fast versions of some stationary iterative methods (such as Gauss-Seidel) consuming O(NlogN) memory and executing an iteration in O(Nlog(2)N) time, N being the number of plane waves used. In a similar way, fast versions of Krylov subspace methods and multigrid methods can also be implemented. These procedures are tested on Poisson's equation expressed in adaptive coordinates. It is found that the best results are obtained with the GMRES method using a multigrid preconditioner with Gauss-Seidel relaxation steps.

  20. Mutation in rod PDE6 linked to congenital stationary night blindness impairs the enzyme inhibition by its gamma-subunit.

    Science.gov (United States)

    Muradov, Khakim G; Granovsky, Alexey E; Artemyev, Nikolai O

    2003-03-25

    Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the vertebrate visual transduction cascade. The activity of rod PDE6 catalytic alpha- and beta-subunits is blocked in the dark by two inhibitory Pgamma-subunits. The inhibition is released upon light-stimulation of photoreceptor cells. Mutation H258N in PDE6beta has been linked to congenital stationary night blindness (CSNB) in a large Danish family (Rambusch pedigree) (Gal, A., Orth, U., Baehr, W., Schwinger, E., and Rosenberg, T. (1994) Nat. Genet. 7, 64-67.) We have analyzed the consequences of this mutation for PDE6 function using a Pgamma-sensitive PDE6alpha'/PDE5 chimera, Chi16. Biochemical analysis of the H257N mutant, an equivalent of PDE6betaH258N, demonstrates that this substitution does not alter the ability of chimeric PDE to dimerize or the enzyme's catalytic properties. The sensitivity of H257N to a competitive inhibitor zaprinast was also unaffected. However, the mutant displayed a significant impairment in the inhibitory interaction with Pgamma, which was apparent from a approximately 20-fold increase in the K(i) value (46 nM) and incomplete maximal inhibition. The inhibitory defect of H257N is not due to perturbation of noncatalytic cGMP binding to the PDE6alpha' GAF domains. The noncatalytic cGMP-binding characteristics of the H257N mutant were similar to those of the parent PDE6alpha'/PDE5 chimera. Since rod PDE6 in the Rambusch CSNB is a catalytic heterodimer of the wild-type PDE6alpha and mutant PDE6beta, Chi16 and H257N were coexpressed, and a heterodimeric PDE, Chi16/H257N, was isolated. It displayed two Pgamma inhibitory sites with the K(i) values of 5 and 57 nM. Our results support the hypothesis that mutation H258N in PDE6beta causes CSNB through incomplete inhibition of PDE6 activity by Pgamma, which leads to desensitization of rod photoreceptors.

  1. Discovery of a novel orally active PDE-4 inhibitor effective in an ovalbumin-induced asthma murine model.

    Science.gov (United States)

    Kwak, Hyun Jeong; Nam, Ji Yeon; Song, Jin Sook; No, Zaesung; Yang, Sung Don; Cheon, Hyae Gyeong

    2012-06-15

    Phosphodiesterase-4 (PDE-4) is responsible for metabolizing adenosine 3',5'-cyclic monophosphate that reduces the activation of a wide range of inflammatory cells including eosinophils. PDE-4 inhibitors are under development for the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Herein, we report a novel PDE-4 inhibitor, PDE-423 (3-[1-(3-cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid), which shows good in vitro and in vivo oral activities. PDE-423 exhibited in vitro IC(50)s of 140 nM and 550 nM in enzyme assay and cell-based assay, respectively. In vivo study using ovalbumin-induced asthmatic mice revealed that PDE-423 reduced methacholine-stimulated airway hyperreactivity in a dose-dependent manner by once daily oral administration (ED(50)=18.3 mg/kg), in parallel with decreased eosinophil peroxidase activity and improved lung histology. In addition, PDE-423 was effective in diminishing lipopolysaccharide-induced neutrophilia in vivo as well as in vitro. Oral administration of PDE-423 (100 mg/kg) had no effect on the duration of xylazine/ketamine-induced anesthesia and did not induce vomiting incidence in ferrets up to the dose of 1000 mg/kg. The present study indicates that a novel PDE-4 inhibitor, PDE-423, has good pharmacological profiles implicating this as a potential candidate for the development of a new anti-asthmatic drug. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Repercussão cardiovascular, com e sem álcool, do carbonato de lodenafila, um novo inibidor da PDE5 Repercusión cardiovascular, con y sin alcohol, del carbonato de lodenafila, un nuevo inhibidor de la PDE5 Cardiovascular repercussion of lodenafil carbonate, a new PDE5 inhibitor, with and without alcohol consumption

    OpenAIRE

    Adauto Carvalho Silva; Odaly Toffoletto; Luiz Antonio Galvão Lucio; Paula Ferreira dos Santos; Jorge Barros Afiune; João Massud Filho; Sergio Tufik

    2010-01-01

    FUNDAMENTO: A disfunção erétil afeta um grande número de homens no mundo e os inibidores de PDE 5 (iPDE5) estão entre os principais métodos de tratamento desses pacientes. O consumo social de álcool e o ato sexual apresentam uma relação considerável. Portanto, a associação entre álcool e iPDE5 pode ocorrer. O carbonato de lodenafila é um novo iPDE5 desenvolvido por uma empresa brasileira. OBJETIVO: Avaliar a repercussão cardiovascular do carbonato de lodenafila, associado ou não ao álcool, as...

  3. Application of alternating decision trees in selecting sparse linear solvers

    KAUST Repository

    Bhowmick, Sanjukta; Eijkhout, Victor; Freund, Yoav; Fuentes, Erika; Keyes, David E.

    2010-01-01

    The solution of sparse linear systems, a fundamental and resource-intensive task in scientific computing, can be approached through multiple algorithms. Using an algorithm well adapted to characteristics of the task can significantly enhance the performance, such as reducing the time required for the operation, without compromising the quality of the result. However, the best solution method can vary even across linear systems generated in course of the same PDE-based simulation, thereby making solver selection a very challenging problem. In this paper, we use a machine learning technique, Alternating Decision Trees (ADT), to select efficient solvers based on the properties of sparse linear systems and runtime-dependent features, such as the stages of simulation. We demonstrate the effectiveness of this method through empirical results over linear systems drawn from computational fluid dynamics and magnetohydrodynamics applications. The results also demonstrate that using ADT can resolve the problem of over-fitting, which occurs when limited amount of data is available. © 2010 Springer Science+Business Media LLC.

  4. Algebraic coarsening methods for linear and nonlinear PDE and systems

    International Nuclear Information System (INIS)

    McWilliams, J C

    2000-01-01

    In [l] Brandt describes a general approach for algebraic coarsening. Given fine-grid equations and a prescribed relaxation method, an approach is presented for defining both the coarse-grid variables and the coarse-grid equations corresponding to these variables. Although, these two tasks are not necessarily related (and, indeed, are often performed independently and with distinct techniques) in the approaches of [1] both revolve around the same underlying observation. To determine whether a given set of coarse-grid variables is appropriate it is suggested that one should employ compatible relaxation. This is a generalization of so-called F-relaxation (e.g., [2]). Suppose that the coarse-grid variables are defined as a subset of the fine-grid variables. Then, F-relaxation simply means relaxing only the F-variables (i.e., fine-grid variables that do not correspond to coarse-grid variables), while leaving the remaining fine-grid variables (C-variables) unchanged. The generalization of compatible relaxation is in allowing the coarse-grid variables to be defined differently, say as linear combinations of fine-grid variables, or even nondeterministically (see examples in [1]). For the present summary it suffices to consider the simple case. The central observation regarding the set of coarse-grid variables is the following [1]: Observation 1--A general measure for the quality of the set of coarse-grid variables is the convergence rate of compatible relaxation. The conclusion is that a necessary condition for efficient multigrid solution (e.g., with convergence rates independent of problem size) is that the compatible-relaxation convergence be bounded away from 1, independently of the number of variables. This is often a sufficient condition, provided that the coarse-grid equations are sufficiently accurate. Therefore, it is suggested in [1] that the convergence rate of compatible relaxation should be used as a criterion for choosing and evaluating the set of coarse

  5. Bounding the electrostatic free energies associated with linear continuum models of molecular solvation.

    Science.gov (United States)

    Bardhan, Jaydeep P; Knepley, Matthew G; Anitescu, Mihai

    2009-03-14

    The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

  6. Bounding the electrostatic free energies associated with linear continuum models of molecular solvation.

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, J. P.; Knepley, M. G.; Anitescu, M. (Biosciences Division); ( MCS); (Rush Univ.)

    2009-03-01

    The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

  7. Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.

    Science.gov (United States)

    Prosdocimi, Tommaso; Mollica, Luca; Donini, Stefano; Semrau, Marta S; Lucarelli, Anna Paola; Aiolfi, Egidio; Cavalli, Andrea; Storici, Paola; Alfei, Silvana; Brullo, Chiara; Bruno, Olga; Parisini, Emilio

    2018-05-01

    Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms.

  8. Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases.

    Science.gov (United States)

    Kalash, Leen; Val, Cristina; Azuaje, Jhonny; Loza, María I; Svensson, Fredrik; Zoufir, Azedine; Mervin, Lewis; Ladds, Graham; Brea, José; Glen, Robert; Sotelo, Eddy; Bender, Andreas

    2017-12-30

    Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A 1 and A 2A receptors (A 1 R and A 2A R) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A 1 and A 2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction and docking, which may be generally applicable to multi-target compound design at several target classes. This approach has identified 2-aminopyridine-3-carbonitriles as the first multi-target ligands at A 1 R, A 2A R and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efficient one-pot scheme and validated pharmacologically as A 1 R/A 2A R-PDE10A ligands, with IC 50 values of 2.4-10.0 μM at PDE10A and K i values of 34-294 nM at A 1 R and/or A 2A R. Furthermore, selectivity profiling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested off-targets. In addition, both compounds 8 and 16 exhibited the desired multi-target profile, which could be considered for further functional efficacy assessment, analog modification for the improvement of selectivity towards A 1 R, A 2A R and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels.

  9. PDE 7 inhibitors: new potential drugs for the therapy of spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Irene Paterniti

    Full Text Available BACKGROUND: Primary traumatic mechanical injury to the spinal cord (SCI causes the death of a number of neurons that to date can neither be recovered nor regenerated. During the last years our group has been involved in the design, synthesis and evaluation of PDE7 inhibitors as new innovative drugs for several neurological disorders. Our working hypothesis is based on two different facts. Firstly, neuroinflammation is modulated by cAMP levels, thus the key role for phosphodiesterases (PDEs, which hydrolyze cAMP, is undoubtedly demonstrated. On the other hand, PDE7 is expressed simultaneously on leukocytes and on the brain, highlighting the potential crucial role of PDE7 as drug target for neuroinflammation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present two chemically diverse families of PDE7 inhibitors, designed using computational techniques such as virtual screening and neuronal networks. We report their biological profile and their efficacy in an experimental SCI model induced by the application of vascular clips (force of 24 g to the dura via a four-level T5-T8 laminectomy. We have selected two candidates, namely S14 and VP1.15, as PDE7 inhibitors. These compounds increase cAMP production both in macrophage and neuronal cell lines. Regarding drug-like properties, compounds were able to cross the blood brain barrier using parallel artificial membranes (PAMPA methodology. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with S14 and VP1.15, two PDE7 inhibitors, significantly reduced the degree of spinal cord inflammation, tissue injury (histological score, and TNF-α, IL-6, COX-2 and iNOS expression. CONCLUSIONS/SIGNIFICANCE: All these data together led us to propose PDE7 inhibitors, and specifically S14 and VP1.15, as potential drug candidates to be further studied for the treatment of SCI.

  10. Some contributions to non-linear physic: Mathematical problems

    International Nuclear Information System (INIS)

    1981-01-01

    The main results contained in this report are the following: i ) Lagrangian universality holds in a precisely defined weak sense. II ) Isolation of 5th order polynomial evolution equations having high order conservation laws. III ) Hamiltonian formulation of a wide class of non-linear evolution equations. IV) Some properties of the symmetries of Gardner-like systems. v) Characterization of the range and Kernel of ζ/ζ u α , |α | - 1. vi) A generalized variational approach and application to the anharmonic oscillator. v II ) Relativistic correction and quasi-classical approximation to the anechoic oscillator. VII ) Properties of a special class of 6th-order anharmonic oscillators. ix) A new method for constructing conserved densities In PDE. (Author) 97 refs

  11. Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation

    Science.gov (United States)

    Gantner, Florian; Götz, Christine; Gekeler, Volker; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

    1998-01-01

    CD19+ B lymphocytes were purified from the peripheral blood of normal and atopic subjects to analyse and compare the phosphodiesterase (PDE) activity profile, PDE mRNA expression and the importance of PDE activity for the regulation of B cell function.The majority of cyclic AMP hydrolyzing activity of human B cells was cytosolic PDE4, followed by cytosolic PDE7-like activity; marginal PDE3 activity was found only in the particulate B cell fraction. PDE1, PDE2 and PDE5 activities were not detected.By cDNA-PCR analysis mRNA of the PDE4 subtypes A, B (splice variant PDE4B2) and D were detected. In addition, a weak signal for PDE3A was found.No differences in PDE activities or mRNA expression of PDE subtypes were found in B cells from either normal or atopic subjects.Stimulation of B lymphocytes with the polyclonal stimulus lipopolysaccharide (LPS) induced a proliferative response in a time- and concentration-dependent manner, which was increased in the presence of interleukin-4 (IL-4). PDE4 inhibitors (rolipram, piclamilast) led to an increase in the cellular cyclic AMP concentration and to an augmentation of proliferation, whereas a PDE3 inhibitor (motapizone) was ineffective, which is in accordance with the PDE profile found. The proliferation enhancing effect of the PDE4 inhibitors was partly mimicked by the cyclic AMP analogues dibutyryl (db) cyclic AMP and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3′,5′-cyclic monophosphorothioate, Sp-isomer (dcl-cBIMPS), respectively. However, at concentrations exceeding 100 μM db-cyclic AMP suppressed B lymphocyte proliferation, probably as a result of cytotoxicity. Prostaglandin E2 (PGE2, 1 μM) and forskolin (10 μM) did not affect B cell proliferation, even when given in combination with rolipram.Inhibition of protein kinase A (PKA) by differentially acting selective inhibitors (KT 5720, Rp-8-Br-cyclic AMPS) decreased the proliferative response of control cells and reversed the proliferation enhancing effects

  12. PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.

    Science.gov (United States)

    Monterisi, Stefania; Lobo, Miguel J; Livie, Craig; Castle, John C; Weinberger, Michael; Baillie, George; Surdo, Nicoletta C; Musheshe, Nshunge; Stangherlin, Alessandra; Gottlieb, Eyal; Maizels, Rory; Bortolozzi, Mario; Micaroni, Massimo; Zaccolo, Manuela

    2017-05-02

    cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.

  13. Combination of 2D/3D ligand-based similarity search in rapid virtual screening from multimillion compound repositories. Selection and biological evaluation of potential PDE4 and PDE5 inhibitors.

    Science.gov (United States)

    Dobi, Krisztina; Hajdú, István; Flachner, Beáta; Fabó, Gabriella; Szaszkó, Mária; Bognár, Melinda; Magyar, Csaba; Simon, István; Szisz, Dániel; Lőrincz, Zsolt; Cseh, Sándor; Dormán, György

    2014-05-28

    Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost effective approach. If structures of active compounds are available rapid 2D similarity search can be performed on multimillion compound databases but the generated library requires further focusing by various 2D/3D chemoinformatics tools. We report here a combination of the 2D approach with a ligand-based 3D method (Screen3D) which applies flexible matching to align reference and target compounds in a dynamic manner and thus to assess their structural and conformational similarity. In the first case study we compared the 2D and 3D similarity scores on an existing dataset derived from the biological evaluation of a PDE5 focused library. Based on the obtained similarity metrices a fusion score was proposed. The fusion score was applied to refine the 2D similarity search in a second case study where we aimed at selecting and evaluating a PDE4B focused library. The application of this fused 2D/3D similarity measure led to an increase of the hit rate from 8.5% (1st round, 47% inhibition at 10 µM) to 28.5% (2nd round at 50% inhibition at 10 µM) and the best two hits had 53 nM inhibitory activities.

  14. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia

    DEFF Research Database (Denmark)

    Grau, Tanja; Artemyev, Nikolai O; Rosenberg, Thomas

    2011-01-01

    study on PDE6C mutations including the mutation spectrum, its prevalence in a large cohort of ACHM/cone dysfunction patients, the clinical phenotype and the functional characterization of mutant PDE6C proteins. Twelve affected patients from seven independent families segregating PDE6C mutations were......Mutations in the gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase (PDE6C) have been recently reported in patients with autosomal recessive inherited achromatopsia (ACHM) and early-onset cone photoreceptor dysfunction. Here we present the results of a comprehensive...... identified in our total patient cohort of 492 independent families. Eleven different PDE6C mutations were found including two nonsense mutations, three mutations affecting transcript splicing as shown by minigene assays, one 1 bp-insertion and five missense mutations. We also performed a detailed functional...

  15. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype.

    Science.gov (United States)

    Libé, Rossella; Horvath, Anelia; Vezzosi, Delphine; Fratticci, Amato; Coste, Joel; Perlemoine, Karine; Ragazzon, Bruno; Guillaud-Bataille, Marine; Groussin, Lionel; Clauser, Eric; Raffin-Sanson, Marie-Laure; Siegel, Jennifer; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Bertagna, Xavier; Bertherat, Jerome; Stratakis, Constantine A

    2011-01-01

    Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

  16. Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.

    Science.gov (United States)

    Chino, Ayaka; Seo, Ryushi; Amano, Yasushi; Namatame, Ichiji; Hamaguchi, Wataru; Honbou, Kazuya; Mihara, Takuma; Yamazaki, Mayako; Tomishima, Masaki; Masuda, Naoyuki

    2018-01-01

    In this study, we report the identification of potent pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties.

  17. Image denoising: Learning the noise model via nonsmooth PDE-constrained optimization

    KAUST Repository

    Reyes, Juan Carlos De los

    2013-11-01

    We propose a nonsmooth PDE-constrained optimization approach for the determination of the correct noise model in total variation (TV) image denoising. An optimization problem for the determination of the weights corresponding to different types of noise distributions is stated and existence of an optimal solution is proved. A tailored regularization approach for the approximation of the optimal parameter values is proposed thereafter and its consistency studied. Additionally, the differentiability of the solution operator is proved and an optimality system characterizing the optimal solutions of each regularized problem is derived. The optimal parameter values are numerically computed by using a quasi-Newton method, together with semismooth Newton type algorithms for the solution of the TV-subproblems. © 2013 American Institute of Mathematical Sciences.

  18. Image denoising: Learning the noise model via nonsmooth PDE-constrained optimization

    KAUST Repository

    Reyes, Juan Carlos De los; Schö nlieb, Carola-Bibiane

    2013-01-01

    We propose a nonsmooth PDE-constrained optimization approach for the determination of the correct noise model in total variation (TV) image denoising. An optimization problem for the determination of the weights corresponding to different types of noise distributions is stated and existence of an optimal solution is proved. A tailored regularization approach for the approximation of the optimal parameter values is proposed thereafter and its consistency studied. Additionally, the differentiability of the solution operator is proved and an optimality system characterizing the optimal solutions of each regularized problem is derived. The optimal parameter values are numerically computed by using a quasi-Newton method, together with semismooth Newton type algorithms for the solution of the TV-subproblems. © 2013 American Institute of Mathematical Sciences.

  19. PdeH, a high-affinity cAMP phosphodiesterase, is a key regulator of asexual and pathogenic differentiation in Magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Ravikrishna Ramanujam

    2010-05-01

    Full Text Available Cyclic AMP-dependent pathways mediate the communication between external stimuli and the intracellular signaling machinery, thereby influencing important aspects of cellular growth, morphogenesis and differentiation. Crucial to proper function and robustness of these signaling cascades is the strict regulation and maintenance of intracellular levels of cAMP through a fine balance between biosynthesis (by adenylate cyclases and hydrolysis (by cAMP phosphodiesterases. We functionally characterized gene-deletion mutants of a high-affinity (PdeH and a low-affinity (PdeL cAMP phosphodiesterase in order to gain insights into the spatial and temporal regulation of cAMP signaling in the rice-blast fungus Magnaporthe oryzae. In contrast to the expendable PdeL function, the PdeH activity was found to be a key regulator of asexual and pathogenic development in M. oryzae. Loss of PdeH led to increased accumulation of intracellular cAMP during vegetative and infectious growth. Furthermore, the pdeHDelta showed enhanced conidiation (2-3 fold, precocious appressorial development, loss of surface dependency during pathogenesis, and highly reduced in planta growth and host colonization. A pdeHDelta pdeLDelta mutant showed reduced conidiation, exhibited dramatically increased (approximately 10 fold cAMP levels relative to the wild type, and was completely defective in virulence. Exogenous addition of 8-Br-cAMP to the wild type simulated the pdeHDelta defects in conidiation as well as in planta growth and development. While a fully functional GFP-PdeH was cytosolic but associated dynamically with the plasma membrane and vesicular compartments, the GFP-PdeL localized predominantly to the nucleus. Based on data from cAMP measurements and Real-Time RTPCR, we uncover a PdeH-dependent biphasic regulation of cAMP levels during early and late stages of appressorial development in M. oryzae. We propose that PdeH-mediated sustenance and dynamic regulation of cAMP signaling

  20. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Nelson, Michael D; Rader, Florian; Tang, Xiu; Tavyev, Jane; Nelson, Stanley F; Miceli, M Carrie; Elashoff, Robert M; Sweeney, H Lee; Victor, Ronald G

    2014-06-10

    To determine whether phosphodiesterase type 5 (PDE5) inhibition can alleviate exercise-induced skeletal muscle ischemia in boys with Duchenne muscular dystrophy (DMD). In 10 boys with DMD and 10 healthy age-matched male controls, we assessed exercise-induced attenuation of reflex sympathetic vasoconstriction, i.e., functional sympatholysis, a protective mechanism that matches oxygen delivery to metabolic demand. Reflex vasoconstriction was induced by simulated orthostatic stress, measured as the decrease in forearm muscle oxygenation with near-infrared spectroscopy, and performed when the forearm muscles were rested or lightly exercised with rhythmic handgrip exercise. Then, the patients underwent an open-label, dose-escalation, crossover trial with single oral doses of tadalafil or sildenafil. The major new findings are 2-fold: first, sympatholysis is impaired in boys with DMD-producing functional muscle ischemia-despite contemporary background therapy with corticosteroids alone or in combination with cardioprotective medication. Second, PDE5 inhibition with standard clinical doses of either tadalafil or sildenafil alleviates this ischemia in a dose-dependent manner. Furthermore, PDE5 inhibition also normalizes the exercise-induced increase in skeletal muscle blood flow (measured by Doppler ultrasound), which is markedly blunted in boys with DMD. These data provide in-human proof of concept for PDE5 inhibition as a putative new therapeutic strategy for DMD. This study provides Class IV evidence that in patients with DMD, PDE5 inhibition restores functional sympatholysis. © 2014 American Academy of Neurology.

  1. In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

    Science.gov (United States)

    Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

    2017-06-16

    Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

  2. The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices

    NARCIS (Netherlands)

    Kistemaker, Loes E M; Oenema, Tjitske A; Baarsma, Hoeke A; Bos, I. Sophie T.; Schmidt, Martina; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Gosens, Reinoud

    2017-01-01

    Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced

  3. Cross-talk between PKA-Cβ and p65 mediates synergistic induction of PDE4B by roflumilast and NTHi

    Science.gov (United States)

    Susuki-Miyata, Seiko; Miyata, Masanori; Lee, Byung-Cheol; Xu, Haidong; Kai, Hirofumi; Yan, Chen; Li, Jian-Dong

    2015-01-01

    Phosphodiesterase 4B (PDE4B) plays a key role in regulating inflammation. Roflumilast, a phosphodiesterase (PDE)4-selective inhibitor, has recently been approved for treating severe chronic obstructive pulmonary disease (COPD) patients with exacerbation. However, there is also clinical evidence suggesting the development of tachyphylaxis or tolerance on repeated dosing of roflumilast and the possible contribution of PDE4B up-regulation, which could be counterproductive for suppressing inflammation. Thus, understanding how PDE4B is up-regulated in the context of the complex pathogenesis and medications of COPD may help improve the efficacy and possibly ameliorate the tolerance of roflumilast. Here we show that roflumilast synergizes with nontypeable Haemophilus influenzae (NTHi), a major bacterial cause of COPD exacerbation, to up-regulate PDE4B2 expression in human airway epithelial cells in vitro and in vivo. Up-regulated PDE4B2 contributes to the induction of certain important chemokines in both enzymatic activity-dependent and activity-independent manners. We also found that protein kinase A catalytic subunit β (PKA-Cβ) and nuclear factor-κB (NF-κB) p65 subunit were required for the synergistic induction of PDE4B2. PKA-Cβ phosphorylates p65 in a cAMP-dependent manner. Moreover, Ser276 of p65 is critical for mediating the PKA-Cβ–induced p65 phosphorylation and the synergistic induction of PDE4B2. Collectively, our data unveil a previously unidentified mechanism underlying synergistic up-regulation of PDE4B2 via a cross-talk between PKA-Cβ and p65 and may help develop new therapeutic strategies to improve the efficacy of PDE4 inhibitor. PMID:25831493

  4. Computer-Aided Transformation of PDE Models: Languages, Representations, and a Calculus of Operations

    Science.gov (United States)

    2016-01-05

    Computer-aided transformation of PDE models: languages, representations, and a calculus of operations A domain-specific embedded language called...languages, representations, and a calculus of operations Report Title A domain-specific embedded language called ibvp was developed to model initial...Computer-aided transformation of PDE models: languages, representations, and a calculus of operations 1 Vision and background Physical and engineered systems

  5. An approach for solving linear fractional programming problems ...

    African Journals Online (AJOL)

    The paper presents a new approach for solving a fractional linear programming problem in which the objective function is a linear fractional function, while the constraint functions are in the form of linear inequalities. The approach adopted is based mainly upon solving the problem algebraically using the concept of duality ...

  6. Gene Therapy in a Large Animal Model of PDE6A-Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Freya M. Mowat

    2017-06-01

    Full Text Available Despite mutations in the rod phosphodiesterase 6-alpha (PDE6A gene being well-recognized as a cause of human retinitis pigmentosa, no definitive treatments have been developed to treat this blinding disease. We performed a trial of retinal gene augmentation in the Pde6a mutant dog using Pde6a delivery by capsid-mutant adeno-associated virus serotype 8, previously shown to have a rapid onset of transgene expression in the canine retina. Subretinal injections were performed in 10 dogs at 29–44 days of age, and electroretinography and vision testing were performed to assess functional outcome. Retinal structure was assessed using color fundus photography, spectral domain optical coherence tomography, and histology. Immunohistochemistry was performed to examine transgene expression and expression of other retinal genes. Treatment resulted in improvement in dim light vision and evidence of rod function on electroretinographic examination. Photoreceptor layer thickness in the treated area was preserved compared with the contralateral control vector treated or uninjected eye. Improved rod and cone photoreceptor survival, rhodopsin localization, cyclic GMP levels and bipolar cell dendrite distribution was observed in treated areas. Some adverse effects including foci of retinal separation, foci of retinal degeneration and rosette formation were identified in both AAV-Pde6a and control vector injected regions. This is the first description of successful gene augmentation for Pde6a retinitis pigmentosa in a large animal model. Further studies will be necessary to optimize visual outcomes and minimize complications before translation to human studies.

  7. [A study of PDE6B gene mutation and phenotype in Chinese cases with retinitis pigmentosa].

    Science.gov (United States)

    Cui, Yun; Zhao, Kan-xing; Wang, Li; Wang, Qing; Zhang, Wei; Chen, Wei-ying; Wang, Li-ming

    2003-01-01

    To identify the mutation spectrum of phosphodiesterase beta subunit (PDE6B) gene, the incidence in Chinese patients with retinitis pigmentosa (RP) and their clinical phenotypic characteristics. Screening of mutations within PDE6B gene was performed using polymerase chain reaction-heteroduplex-single strand conformation polymorphism (PCR-SSCP) and DNA sequence in 35 autosomal recessive (AR) RP and 55 sporadic RP cases. The phenotypes of the patients with the gene mutation were examined and analyzed. Novel complex heterozygous variants of PDE6B gene in a sporadic case, a T to C transversion in codon 323 resulting in the substitution of Gly by Ser and 2 base pairs (bp: G and T) insert between the 27th-28th bp upstream of the 5'-end of exon 10 were both present in a same isolate RP. But they are not found in 100 unrelated healthy individuals. Ocular findings showed diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi, optic atrophy and vessel attenuation. Multi-focal ERG indicated that the rod function was more severely deteriorated. A mutation was found in a case with RP in a ARRP family, a G to A transversion at 19th base upstream 5'-end of exon 11 (within intron 10) of PDE6B gene. A sporadic RP carried a sequence variant of PDE6B gene, a G to C transition, at the 15th base adjacent to the 3'-end of exon l8. In another isolate case with RP was found 2 bp (GT) insert between 31st and 32nd base upstream 5'-end of exon 4 (in intron 3) of PDE6B gene. There are novel complex heterozygous mutations of PDE6B gene responsible for a sporadic RP patient in China. This gene mutation associated with rod deterioration and RP. Several DNA variants were found in introns of PDE6B gene in national population.

  8. An Approach for Solving Linear Fractional Programming Problems

    OpenAIRE

    Andrew Oyakhobo Odior

    2012-01-01

    Linear fractional programming problems are useful tools in production planning, financial and corporate planning, health care and hospital planning and as such have attracted considerable research interest. The paper presents a new approach for solving a fractional linear programming problem in which the objective function is a linear fractional function, while the constraint functions are in the form of linear inequalities. The approach adopted is based mainly upon solving the problem algebr...

  9. 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.

  10. 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.

  11. A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin

    Directory of Open Access Journals (Sweden)

    Mauro M Teixeira

    1997-12-01

    Full Text Available The elevation of intracellular cyclic AMP by phosphodiesterase (PDE4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibt eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo.

  12. A linear algebraic approach to electron-molecule collisions

    International Nuclear Information System (INIS)

    Collins, L.A.; Schnieder, B.I.

    1982-01-01

    The linear algebraic approach to electron-molecule collisions is examined by firstly deriving the general set of coupled integrodifferential equations that describe electron collisional processes and then describing the linear algebraic approach for obtaining a solution to the coupled equations. Application of the linear algebraic method to static-exchange, separable exchange and effective optical potential, is examined. (U.K.)

  13. Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

    OpenAIRE

    Brown, Kim M.; Lee, Louisa C.Y; Findlay, Jane E.; Day, Jonathan P.; Baillie, George S.

    2012-01-01

    The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kin...

  14. PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.

    Science.gov (United States)

    Lehrke, Michael; Kahles, Florian; Makowska, Anna; Tilstam, Pathricia V; Diebold, Sebastian; Marx, Judith; Stöhr, Robert; Hess, Katharina; Endorf, Elizabeth B; Bruemmer, Dennis; Marx, Nikolaus; Findeisen, Hannes M

    2015-04-01

    Phosphodiesterase 4 (PDE4) activity mediates cAMP-dependent smooth muscle cell (SMC) activation following vascular injury. In this study we have investigated the effects of specific PDE4 inhibition with roflumilast on SMC proliferation and inflammatory activation in vitro and neointima formation following guide wire-induced injury of the femoral artery in mice in vivo. In vitro, roflumilast did not affect SMC proliferation, but diminished TNF-α induced expression of the vascular cell adhesion molecule 1 (VCAM-1). Specific activation of the cAMP effector Epac, but not PKA activation mimicked the effects of roflumilast on VCAM-1 expression. Consistently, the reduction of VCAM-1 expression was rescued following inhibition of Epac. TNF-α induced NFκB p65 translocation and VCAM-1 promoter activity were not altered by roflumilast in SMCs. However, roflumilast treatment and Epac activation repressed the induction of the activating epigenetic histone mark H3K4me2 at the VCAM-1 promoter, while PKA activation showed no effect. Furthermore, HDAC inhibition blocked the inhibitory effect of roflumilast on VCAM-1 expression. Both, roflumilast and Epac activation reduced monocyte adhesion to SMCs in vitro. Finally, roflumilast treatment attenuated femoral artery intima-media ratio by more than 50% after 4weeks. In summary, PDE4 inhibition regulates VCAM-1 through a novel Epac-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury. PDE4 inhibition and Epac activation might represent novel approaches for the treatment of vascular diseases, including atherosclerosis and in-stent restenosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Introducing linear functions: an alternative statistical approach

    Science.gov (United States)

    Nolan, Caroline; Herbert, Sandra

    2015-12-01

    The introduction of linear functions is the turning point where many students decide if mathematics is useful or not. This means the role of parameters and variables in linear functions could be considered to be `threshold concepts'. There is recognition that linear functions can be taught in context through the exploration of linear modelling examples, but this has its limitations. Currently, statistical data is easily attainable, and graphics or computer algebra system (CAS) calculators are common in many classrooms. The use of this technology provides ease of access to different representations of linear functions as well as the ability to fit a least-squares line for real-life data. This means these calculators could support a possible alternative approach to the introduction of linear functions. This study compares the results of an end-of-topic test for two classes of Australian middle secondary students at a regional school to determine if such an alternative approach is feasible. In this study, test questions were grouped by concept and subjected to concept by concept analysis of the means of test results of the two classes. This analysis revealed that the students following the alternative approach demonstrated greater competence with non-standard questions.

  16. Linderane Suppresses Hepatic Gluconeogenesis by Inhibiting the cAMP/PKA/CREB Pathway Through Indirect Activation of PDE 3 via ERK/STAT3

    Directory of Open Access Journals (Sweden)

    Wei Xie

    2018-05-01

    Full Text Available The role of phosphodiesterase 3 (PDE3, a cyclic AMP (cAMP-degrading enzyme, in modulating gluconeogenesis remains unknown. Here, linderane, a natural compound, was found to inhibit gluconeogenesis by activating hepatic PDE3 in rat primary hepatocytes. The underlying molecular mechanism and its effects on whole-body glucose and lipid metabolism were investigated. The effect of linderane on gluconeogenesis, cAMP content, phosphorylation of cAMP-response element-binding protein (CREB and PDE activity were examined in cultured primary hepatocytes and C57BL/6J mice. The precise mechanism by which linderane activates PDE3 and inhibits the cAMP pathway was explored using pharmacological inhibitors. The amelioration of metabolic disorders was observed in ob/ob mice. Linderane inhibited gluconeogenesis, reduced phosphoenolpyruvate carboxykinase (Pck1 and glucose-6-phosphatase (G6pc gene expression, and decreased intracellular cAMP concentration and CREB phosphorylation in rat primary hepatocytes under both basal and forskolin-stimulated conditions. In rat primary hepatocytes, it also increased total PDE and PDE3 activity but not PDE4 activity. The suppressive effect of linderane on the cAMP pathway and gluconeogenesis was abolished by the non-specific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX and the specific PDE3 inhibitor cilostazol. Linderane indirectly activated PDE3 through extracellular regulated protein kinase 1/2 (ERK1/2 and signal transducer and activator of transcription 3 (STAT3 activation. Linderane improved glucose and lipid metabolism after chronic oral administration in ob/ob mice. Our findings revealed linderane as an indirect PDE3 activator that suppresses gluconeogenesis through cAMP pathway inhibition and has beneficial effects on metabolic syndromes in ob/ob mice. This investigation highlighted the potential for PDE3 activation in the treatment of type 2 diabetes.

  17. A General Symbolic PDE Solver Generator: Beyond Explicit Schemes

    Directory of Open Access Journals (Sweden)

    K. Sheshadri

    2003-01-01

    Full Text Available This paper presents an extension of our Mathematica- and MathCode-based symbolic-numeric framework for solving a variety of partial differential equation (PDE problems. The main features of our earlier work, which implemented explicit finite-difference schemes, include the ability to handle (1 arbitrary number of dependent variables, (2 arbitrary dimensionality, and (3 arbitrary geometry, as well as (4 developing finite-difference schemes to any desired order of approximation. In the present paper, extensions of this framework to implicit schemes and the method of lines are discussed. While C++ code is generated, using the MathCode system for the implicit method, Modelica code is generated for the method of lines. The latter provides a preliminary PDE support for the Modelica language. Examples illustrating the various aspects of the solver generator are presented.

  18. Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A).

    Science.gov (United States)

    Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R

    2013-11-14

    Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

  19. Plano de Desenvolvimento da Escola (PDE-Escola): ferramenta de autonomia escolar?

    OpenAIRE

    Schimonek, Elisangela Maria Pereira; Muranaka, Maria Aparecida Segatto

    2013-01-01

    Resumo O presente artigo objetiva promover uma análise da implantação do PDE-Escola em duas unidades educacionais do município de Limeira-SP, que apresentaram o IDEB/2007 abaixo da média nacional e que foram direcionadas a implantar o Programa a partir de 2009. O PDE-Escola trata-se de um programa do Governo Federal que se proclama capaz de viabilizar a autonomia, a obtenção de melhores resultados educacionais e a modernização da estrutura, organização e gestão escolar a partir da adoção d...

  20. Effects of PDE5 Inhibitors and sGC Stimulators in a Rat Model of Artificial Ureteral Calculosis.

    Directory of Open Access Journals (Sweden)

    Peter Sandner

    Full Text Available Urinary colics from calculosis are frequent and intense forms of pain whose current pharmacological treatment remains unsatisfactory. New and more effective drugs are needed to control symptoms and improve stone expulsion. Recent evidence suggested that the Nitric Oxide (NO / cyclic guanosine monophosphate (cGMP/phosphodiesterase type 5 (PDE5 system may contribute to ureteral motility influencing stone expulsion. We investigated if PDE5 inhibitors and sGC stimulators influence ureteral contractility, pain behaviour and stone expulsion in a rat model of ureteral calculosis. We investigated: a the sex-specific PDE5 distribution in the rat ureter; b the functional in vitro effects of vardenafil and sildenafil (PDE5 inhibitors and BAY41-2272 (sGC stimulator on induced ureteral contractility in rats and c the in vivo effectiveness of vardenafil and BAY41-2272, alone and combined with ketoprofen, vs hyoscine-N-butylbromide alone or combined with ketoprofen, on behavioural pain indicators and stone expulsion in rats with artificial calculosis in one ureter. PDE5 was abundantly expressed in male and female rats' ureter. In vitro, both vardenafil and BAY41-2272 significantly relaxed pre-contracted ureteral strips. In vivo, all compounds significantly reduced number and global duration of "ureteral crises" and post-stone lumbar muscle hyperalgesia in calculosis rats. The highest level of reduction of the pain behaviour was observed with BAY41-2272 among all spasmolytics administered alone, and with the combination of ketoprofen with BAY41-2272. The percentage of stone expulsion was maximal in the ketoprofen+BAY41-2272 group. The NO/cGMP/PDE5 pathway is involved in the regulation of ureteral contractility and pain behaviour in urinary calculosis. PDE5 inhibitors and sGC stimulators could become a potent new option for treatment of urinary colic pain.

  1. Repercussão cardiovascular, com e sem álcool, do carbonato de lodenafila, um novo inibidor da PDE5

    OpenAIRE

    Silva, Adauto Carvalho; Toffoletto, Odaly; Lucio, Luiz Antonio Galvão; Santos, Paula Ferreira dos; Afiune, Jorge Barros; Massud Filho, João; Tufik, Sergio

    2010-01-01

    FUNDAMENTO: A disfunção erétil afeta um grande número de homens no mundo e os inibidores de PDE 5 (iPDE5) estão entre os principais métodos de tratamento desses pacientes. O consumo social de álcool e o ato sexual apresentam uma relação considerável. Portanto, a associação entre álcool e iPDE5 pode ocorrer. O carbonato de lodenafila é um novo iPDE5 desenvolvido por uma empresa brasileira. OBJETIVO: Avaliar a repercussão cardiovascular do carbonato de lodenafila, associado ou não ao álcool, as...

  2. Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: tuz@mir.wustl.edu; Xu Jinbin; Jones, Lynne A.; Li Shihong; Mach, Robert H. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2010-05-15

    Papaverine, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, a specific inhibitor of phosphodiesterase (PDE) 10A with IC{sub 50} values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A. Here, we report the radiosynthesis of [{sup 11}C]papaverine and the in vitro and in vivo evaluation of [{sup 11}C]papaverine as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of papaverine with {sup 11}C was achieved by O-methylation of the corresponding des-methyl precursor with [{sup 11}C]methyl iodide. [{sup 11}C]papaverine was obtained with {approx}70% radiochemical yield and a specific activity >10 Ci/{mu}mol. In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of [{sup 11}C]papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of [{sup 11}C]papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of [{sup 11}C]papaverine from brain. Our initial evaluation suggests that despite papaverine's utility for in vitro studies and as a pharmaceutical tool, [{sup 11}C]papaverine is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Analogs of papaverine having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

  3. The Person-Event Data Environment (PDE: Leveraging Big Data for Studies of Psychological Strengths in Soldiers

    Directory of Open Access Journals (Sweden)

    Loryana L. Vie

    2013-12-01

    Full Text Available The Department of Defense (DoD strives to efficiently manage the large volumes of administrative data collected and repurpose this information for research and analyses with policy implications. This need is especially present in the United States Army, which maintains numerous electronic databases with information on more than one million Active-Duty, Reserve, and National Guard soldiers, their family members, and Army civilian employees. The accumulation of vast amounts of digitized health, military service, and demographic data thus approaches, and may even exceed, traditional benchmarks for Big Data. Given the challenges of disseminating sensitive personal and health information, the Person-Event Data Environment (PDE was created to unify disparate Army and DoD databases in a secure cloud-based enclave. This electronic repository serves the ultimate goal of achieving cost efficiencies in psychological and healthcare studies and provides a platform for collaboration among diverse scientists. This paper provides an overview of the uses of the PDE to perform command surveillance and policy analysis for Army leadership. The paper highlights the confluence of both economic and behavioral science perspectives elucidating empirically-based studies examining relations between psychological assets, health, and healthcare utilization. Specific examples explore the role of psychological assets in major cost drivers such as medical expenditures both during deployment and stateside, drug use, attrition from basic training, and low reenlistment rates. Through creation of the PDE, the Army and scientific community can now capitalize on the vast amounts of personnel, financial, medical, training and education, deployment and security systems that influence Army-wide policies and procedures.

  4. Role of Ser102 and Ser104 as Regulators of cGMP Hydrolysis by PDE5A

    DEFF Research Database (Denmark)

    Carøe Nordgaard, Julie; Kruse, Lars Schack; Gammeltoft, Steen

    2014-01-01

    -N-AS neuroblastoma cells as C-terminal fusions with green fluorescent protein. Transfected cells were treated with sildenafil, cilostazol, glyceryl trinitrate, calcitonin gene-related peptide (CGRP) or sumatriptan. PDE5A-GFP fusion proteins were localized in fixed cells by immunofluorescence and PDE activity...

  5. Phosphodiesterase (PDE5) inhibition assay for rapid detection of erectile dysfunction drugs and analogs in sexual enhancement products.

    Science.gov (United States)

    Santillo, Michael F; Mapa, Mapa S T

    2018-02-28

    Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase-5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC 50 , 0.4-4.0 ng mL -1 ), demonstrating sensitive detection in matrix-free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g -1 , which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad-based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex-enhancement products. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  6. Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

    Science.gov (United States)

    Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

    2018-05-01

    Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

  7. New approach to solve symmetric fully fuzzy linear systems

    Indian Academy of Sciences (India)

    concepts of fuzzy set theory and then define a fully fuzzy linear system of equations. .... To represent the above problem as fully fuzzy linear system, we represent x .... Fully fuzzy linear systems can be solved by Linear programming approach, ...

  8. The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices.

    Science.gov (United States)

    Kistemaker, Loes E M; Oenema, Tjitske A; Baarsma, Hoeke A; Bos, I Sophie T; Schmidt, Martina; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Gosens, Reinoud

    2017-09-01

    Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodeling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Guinea pig precision-cut lung slices were preincubated with the PDE4 inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 μM) or TGF-β 1 (2 ng/ml) for 48 h. The inhibitory effects on airway smooth muscle remodeling, airway contraction, and TGF-β release were investigated. Methacholine-induced protein expression of smooth muscle-myosin was fully inhibited by CHF-6001 (0.3-100 nM), whereas roflumilast (1 µM) had smaller effects. Tiotropium and glycopyrrolate fully inhibited methacholine-induced airway remodeling (0.1-30 nM). The combination of CHF-6001 and tiotropium or glycopyrrolate, in concentrations partially effective by themselves, fully inhibited methacholine-induced remodeling in combination. CHF-6001 did not affect airway closure and had limited effects on TGF-β 1 -induced remodeling, but rather, it inhibited methacholine-induced TGF-β release. The PDE4 inhibitor CHF-6001, and to a lesser extent roflumilast, and the LAMAs tiotropium and glycopyrrolate inhibit bronchoconstriction-induced remodeling. The combination of CHF-6001 and anticholinergics was more effective than the individual compounds. This cooperativity might be explained by the distinct mechanisms of action inhibiting TGF-β release and bronchoconstriction. Copyright © 2017 the American Physiological Society.

  9. [Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review].

    Science.gov (United States)

    Bacconi, L; Gressier, F

    2017-02-01

    function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  10. Fuzzy Multi-objective Linear Programming Approach

    Directory of Open Access Journals (Sweden)

    Amna Rehmat

    2007-07-01

    Full Text Available Traveling salesman problem (TSP is one of the challenging real-life problems, attracting researchers of many fields including Artificial Intelligence, Operations Research, and Algorithm Design and Analysis. The problem has been well studied till now under different headings and has been solved with different approaches including genetic algorithms and linear programming. Conventional linear programming is designed to deal with crisp parameters, but information about real life systems is often available in the form of vague descriptions. Fuzzy methods are designed to handle vague terms, and are most suited to finding optimal solutions to problems with vague parameters. Fuzzy multi-objective linear programming, an amalgamation of fuzzy logic and multi-objective linear programming, deals with flexible aspiration levels or goals and fuzzy constraints with acceptable deviations. In this paper, a methodology, for solving a TSP with imprecise parameters, is deployed using fuzzy multi-objective linear programming. An example of TSP with multiple objectives and vague parameters is discussed.

  11. N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes

    Science.gov (United States)

    Jang, Deok-Jin; Park, Soo-Won; Lee, Jin-A; Lee, Changhoon; Chae, Yeon-Su; Park, Hyungju; Kim, Min-Jeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong-Kiun

    2010-01-01

    Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the…

  12. Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

    Science.gov (United States)

    Goto, Taiji; Shiina, Akiko; Yoshino, Toshiharu; Mizukami, Kiyoshi; Hirahara, Kazuki; Suzuki, Osamu; Sogawa, Yoshitaka; Takahashi, Tomoko; Mikkaichi, Tsuyoshi; Nakao, Naoki; Takahashi, Mizuki; Hasegawa, Masashi; Sasaki, Shigeki

    2013-11-15

    5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50=200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50=8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia in mice (ID50=16 mg/kg, ip). Furthermore, based on the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we designed 7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one derivative 39 which has a fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory activity against LPS-induced tumor necrosis factor alpha (TNF-α) production in mouse splenocytes (IC50=0.21 nM) and in vivo anti-inflammatory activity against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of 1.0 mg/kg, i.t.). Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Modeling and Simulation of High Dimensional Stochastic Multiscale PDE Systems at the Exascale

    Energy Technology Data Exchange (ETDEWEB)

    Kevrekidis, Ioannis [Princeton Univ., NJ (United States)

    2017-03-22

    The thrust of the proposal was to exploit modern data-mining tools in a way that will create a systematic, computer-assisted approach to the representation of random media -- and also to the representation of the solutions of an array of important physicochemical processes that take place in/on such media. A parsimonious representation/parametrization of the random media links directly (via uncertainty quantification tools) to good sampling of the distribution of random media realizations. It also links directly to modern multiscale computational algorithms (like the equation-free approach that has been developed in our group) and plays a crucial role in accelerating the scientific computation of solutions of nonlinear PDE models (deterministic or stochastic) in such media – both solutions in particular realizations of the random media, and estimation of the statistics of the solutions over multiple realizations (e.g. expectations).

  14. PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its transcription is up-regulated by androgens in HepG2

    Directory of Open Access Journals (Sweden)

    Emmanuel eStrahm

    2014-05-01

    Full Text Available Most androgenic drugs are available as esters for a prolonged depot action. However the enzymes involved in the hydrolysis of the esters have not been identified. There is one study indicating that PDE7B may be involved in the activation of testosterone enanthate. The aims are to identify the cellular compartments where the hydrolysis of testosterone enanthate and nandrolone decanoate occurs, and to investigate the involvement of PDE7B in the activation. We also determined if testosterone and nandrolone affect the expression of the PDE7B gene. The hydrolysis studies were performed in isolated human liver cytosolic and microsomal preparations with and without specific PDE7B inhibitor. The gene expression was studied in human hepatoma cells (HepG2 exposed to testosterone and nandrolone. We show that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol. The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 hours exposure to 1 µM testosterone enanthate and nandrolone decanoate, respectively. These results show that PDE7B is involved in the activation of esterified nandrolone and testosterone and that the gene expression of PDE7B is induced by supra-physiological concentrations of androgenic drugs.

  15. An overset grid approach to linear wave-structure interaction

    DEFF Research Database (Denmark)

    Read, Robert; Bingham, Harry B.

    2012-01-01

    A finite-difference based approach to wave-structure interaction is reported that employs the overset approach to grid generation. A two-dimensional code that utilizes the Overture C++ library has been developed to solve the linear radiation problem for a floating body of arbitrary form. This sof......A finite-difference based approach to wave-structure interaction is reported that employs the overset approach to grid generation. A two-dimensional code that utilizes the Overture C++ library has been developed to solve the linear radiation problem for a floating body of arbitrary form...

  16. PERSEPSI PENGOLAH DATA TERHADAP EFEKTIVITAS PDE HOTEL BERBINTANG DI KOTA DENPASAR

    Directory of Open Access Journals (Sweden)

    I KETUT SUWARTHA

    2010-07-01

    Full Text Available The development of information technology provides more expectations for the businessman, spesifically in the hotel sector. Nevertheless, in it’s implementation raise expectation gap between the user of the information and data processing in the Electronic Data Processing (PDE. The objective of this research is to find out the effectivity and dimension that should be improved on the side of data processing perception in the Electronic Data Processing (PDE of  star hotels  in Denpasar. The data collected by using questionnaire and interview and the data analysis technique used in this research is quantitative analysis technique. The conclusions from the analysis are (1 data processing perception included in the category of very effective by 81.64%, (2 there are three dimensions which needs more attention and improved, namely time dimension, report variation dimension or out put, information quality dimension.

  17. Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation.

    Science.gov (United States)

    Carvalheira, Ana A; Pereira, Nuno Monteiro; Maroco, João; Forjaz, Vera

    2012-09-01

    Phosphodiesterase type 5 inhibitors (PDE5) are currently the first line treatment for erectile dysfunction (ED). However, previous research shows that PDE5 treatments have high discontinuation rates. Understanding the reasons for discontinuing PDE5 will be necessary to optimize the response to treatment. The main goals were: (i) to analyze discontinuation rate of PDE5; (ii) to identify the discontinuation predictors; and (iii) to study the reasons for discontinuation using a qualitative methodology. The PDE5 discontinuation rates, predictors, and reasons for discontinuation treatment. A total of 327 men with clinical diagnosis for ED who had been treated with PDE5 were successfully interviewed by telephone, after giving their informed consent by snail mail. Telephone interviews, concerning their ongoing treatment, were carried out using a standardized questionnaire form with quantitative and qualitative items. Participation rate was 71.8%. Of the total sample, 160 men (48.9%) had discontinued PDE5 treatment. The discontinuation rate was higher among men with diabetes (73%) and in iatrogenic group (65%), and lower in venogenic etiology (38.7%). We differentiated three groups of men who discontinued treatment (i) during the first 3 months (55.1%); (ii) between 4 and 12 months (26.9%); and (iii) after a period of 12 months (18%). Qualitative analyses revealed diverse reasons for discontinuation: non-effectiveness of PDE5 (36.8%), psychological factors (e.g., anxiety, negative emotions, fears, concerns, dysfunctional beliefs) (17.5%), erection recovery (14.4%), and concerns about the cardiovascular safety of PDE5 (8.7%) were the most common. Older men and men whose partners were involved in the treatment, were less likely to discontinue treatment. Half the subjects discontinued medication. Mostly, there was a combination of factors that led to discontinuation: non-effectiveness and psychosocial factors appear to be the main reasons. Addressing those factors will allow

  18. Linear and nonlinear stability criteria for compressible MHD flows in a gravitational field

    Science.gov (United States)

    Moawad, S. M.; Moawad

    2013-10-01

    The equilibrium and stability properties of ideal magnetohydrodynamics (MHD) of compressible flow in a gravitational field with a translational symmetry are investigated. Variational principles for the steady-state equations are formulated. The MHD equilibrium equations are obtained as critical points of a conserved Lyapunov functional. This functional consists of the sum of the total energy, the mass, the circulation along field lines (cross helicity), the momentum, and the magnetic helicity. In the unperturbed case, the equilibrium states satisfy a nonlinear second-order partial differential equation (PDE) associated with hydrodynamic Bernoulli law. The PDE can be an elliptic or a parabolic equation depending on increasing the poloidal flow speed. Linear and nonlinear Lyapunov stability conditions under translational symmetric perturbations are established for the equilibrium states.

  19. Development of a Scintillation Proximity Assay (SPA) Based, High Throughput Screening Feasible Method for the Identification of PDE12 Activity Modulators.

    Science.gov (United States)

    Mang, Samuel; Bucher, Hannes; Nickolaus, Peter

    2016-01-01

    The scintillation proximity assay (SPA) technology has been widely used to establish high throughput screens (HTS) for a range of targets in the pharmaceutical industry. PDE12 (aka. 2'- phosphodiesterase) has been published to participate in the degradation of oligoadenylates that are involved in the establishment of an antiviral state via the activation of ribonuclease L (RNAse-L). Degradation of oligoadenylates by PDE12 terminates these antiviral activities, leading to decreased resistance of cells for a variety of viral pathogens. Therefore inhibitors of PDE12 are discussed as antiviral therapy. Here we describe the use of the yttrium silicate SPA bead technology to assess inhibitory activity of compounds against PDE12 in a homogeneous, robust HTS feasible assay using tritiated adenosine-P-adenylate ([3H]ApA) as substrate. We found that the used [3H]ApA educt, was not able to bind to SPA beads, whereas the product [3H]AMP, as known before, was able to bind to SPA beads. This enables the measurement of PDE12 activity on [3H]ApA as a substrate using a wallac microbeta counter. This method describes a robust and high throughput capable format in terms of specificity, commonly used compound solvents, ease of detection and assay matrices. The method could facilitate the search for PDE12 inhibitors as antiviral compounds.

  20. A Proposed Stochastic Finite Difference Approach Based on Homogenous Chaos Expansion

    Directory of Open Access Journals (Sweden)

    O. H. Galal

    2013-01-01

    Full Text Available This paper proposes a stochastic finite difference approach, based on homogenous chaos expansion (SFDHC. The said approach can handle time dependent nonlinear as well as linear systems with deterministic or stochastic initial and boundary conditions. In this approach, included stochastic parameters are modeled as second-order stochastic processes and are expanded using Karhunen-Loève expansion, while the response function is approximated using homogenous chaos expansion. Galerkin projection is used in converting the original stochastic partial differential equation (PDE into a set of coupled deterministic partial differential equations and then solved using finite difference method. Two well-known equations were used for efficiency validation of the method proposed. First one being the linear diffusion equation with stochastic parameter and the second is the nonlinear Burger's equation with stochastic parameter and stochastic initial and boundary conditions. In both of these examples, the probability distribution function of the response manifested close conformity to the results obtained from Monte Carlo simulation with optimized computational cost.

  1. Use of the KlADH3 promoter for the quantitative production of the murine PDE5A isoforms in the yeast Kluyveromyces lactis.

    Science.gov (United States)

    Cardarelli, Silvia; Giorgi, Mauro; Naro, Fabio; Malatesta, Francesco; Biagioni, Stefano; Saliola, Michele

    2017-09-22

    Phosphodiesterases (PDE) are a superfamily of enzymes that hydrolyse cyclic nucleotides (cAMP/cGMP), signal molecules in transduction pathways regulating crucial aspects of cell life. PDEs regulate the intensity and duration of the cyclic nucleotides signal modulating the downstream biological effect. Due to this critical role associated with the extensive distribution and multiplicity of isozymes, the 11 mammalian families (PDE1 to PDE11) constitute key therapeutic targets. PDE5, one of these cGMP-specific hydrolysing families, is the molecular target of several well known drugs used to treat erectile dysfunction and pulmonary hypertension. Kluyveromyces lactis, one of the few yeasts capable of utilizing lactose, is an attractive host alternative to Saccharomyces cerevisiae for heterologous protein production. Here we established K. lactis as a powerful host for the quantitative production of the murine PDE5 isoforms. Using the promoter of the highly expressed KlADH3 gene, multicopy plasmids were engineered to produce the native and recombinant Mus musculus PDE5 in K. lactis. Yeast cells produced large amounts of the purified A1, A2 and A3 isoforms displaying K m , V max and Sildenafil inhibition values similar to those of the native murine enzymes. PDE5 whose yield was nearly 1 mg/g wet weight biomass for all three isozymes (30 mg/L culture), is well tolerated by K. lactis cells without major growth deficiencies and interferences with the endogenous cAMP/cGMP signal transduction pathways. To our knowledge, this is the first time that the entire PDE5 isozymes family containing both regulatory and catalytic domains has been produced at high levels in a heterologous eukaryotic organism. K. lactis has been shown to be a very promising host platform for large scale production of mammalian PDEs for biochemical and structural studies and for the development of new specific PDE inhibitors for therapeutic applications in many pathologies.

  2. Improving Fiber Alignment in HARDI by Combining Contextual PDE Flow with Constrained Spherical Deconvolution.

    Directory of Open Access Journals (Sweden)

    J M Portegies

    Full Text Available We propose two strategies to improve the quality of tractography results computed from diffusion weighted magnetic resonance imaging (DW-MRI data. Both methods are based on the same PDE framework, defined in the coupled space of positions and orientations, associated with a stochastic process describing the enhancement of elongated structures while preserving crossing structures. In the first method we use the enhancement PDE for contextual regularization of a fiber orientation distribution (FOD that is obtained on individual voxels from high angular resolution diffusion imaging (HARDI data via constrained spherical deconvolution (CSD. Thereby we improve the FOD as input for subsequent tractography. Secondly, we introduce the fiber to bundle coherence (FBC, a measure for quantification of fiber alignment. The FBC is computed from a tractography result using the same PDE framework and provides a criterion for removing the spurious fibers. We validate the proposed combination of CSD and enhancement on phantom data and on human data, acquired with different scanning protocols. On the phantom data we find that PDE enhancements improve both local metrics and global metrics of tractography results, compared to CSD without enhancements. On the human data we show that the enhancements allow for a better reconstruction of crossing fiber bundles and they reduce the variability of the tractography output with respect to the acquisition parameters. Finally, we show that both the enhancement of the FODs and the use of the FBC measure on the tractography improve the stability with respect to different stochastic realizations of probabilistic tractography. This is shown in a clinical application: the reconstruction of the optic radiation for epilepsy surgery planning.

  3. Some contributions to non-linear physic: Mathematical problems; Contribuciones a problemas matematicos en fisica no-lineal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1981-07-01

    The main results contained in this report are the following: i ) Lagrangian universality holds in a precisely defined weak sense. II ) Isolation of 5th order polynomial evolution equations having high order conservation laws. III ) Hamiltonian formulation of a wide class of non-linear evolution equations. IV) Some properties of the symmetries of Gardner-like systems. v) Characterization of the range and Kernel of {zeta}/{zeta} u{sub {alpha}}, |{alpha} | - 1. vi) A generalized variational approach and application to the anharmonic oscillator. v II ) Relativistic correction and quasi-classical approximation to the anechoic oscillator. VII ) Properties of a special class of 6th-order anharmonic oscillators. ix) A new method for constructing conserved densities In PDE. (Author) 97 refs.

  4. Collocation methods for uncertainty quanti cation in PDE models with random data

    KAUST Repository

    Nobile, Fabio

    2014-01-01

    address interpolatory approximations where the PDE is solved on a sparse grid of Gauss points in the probability space and the solutions thus obtained interpolated by multivariate polynomials. We present recent results on optimized sparse grids in which

  5. The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium.

    Directory of Open Access Journals (Sweden)

    Øivind Ørstavik

    Full Text Available We recently published that the positive inotropic response (PIR to levosimendan can be fully accounted for by phosphodiesterase (PDE inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD, levosimendan and other PDE inhibitors.Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.OR-1896 evoked a maximum PIR of 33 ± 10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89 ± 14% and absent in the presence of the PDE3 inhibitors cilostamide (0.5 ± 5.3% or milrinone (3.2 ± 4.4%. The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic effect of levosimendan, nor of its main metabolite OR-1896.

  6. The pde2 gene of Saccharomyces cerevisiae is allelic to rca1 and encodes a phosphodiesterase which protects the cell from extracellular cAMP.

    Science.gov (United States)

    Wilson, R B; Renault, G; Jacquet, M; Tatchell, K

    1993-07-05

    The high affinity cAMP phosphodiesterase, encoded by PDE2, is an important component of the cAMP-dependent protein kinase signaling system in Saccharomyces cerevisiae. An unexpected phenotype of pde2 mutants is sensitivity to external cAMP. This trait has been found independently for rca1 mutants and has been used to monitor the effects of cAMP on several biological processes. We demonstrate here that RCA1 is identical to PDE2. Further analysis of the phenotype of pde2 deletions reveal that exogenously added cAMP results in an increase in the internal level of cAMP. This increase slows down the rate of cell division by increasing the length of the G1 phase of the cell cycle and leads to increased cell volume. Also, cells with a disrupted PDE2 gene previously arrested by nutrient starvation rapidly lose thermotolerance when incubated with exogenous cAMP. From these observations we propose that a role of the PDE2-encoded phosphodiesterase may be to help insulate the internal cAMP pools from the external environment. This protective role might also be important in other eukaryotic organisms where cAMP is a key second messenger.

  7. 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”...

  8. AZTEC: A parallel iterative package for the solving linear systems

    Energy Technology Data Exchange (ETDEWEB)

    Hutchinson, S.A.; Shadid, J.N.; Tuminaro, R.S. [Sandia National Labs., Albuquerque, NM (United States)

    1996-12-31

    We describe a parallel linear system package, AZTEC. The package incorporates a number of parallel iterative methods (e.g. GMRES, biCGSTAB, CGS, TFQMR) and preconditioners (e.g. Jacobi, Gauss-Seidel, polynomial, domain decomposition with LU or ILU within subdomains). Additionally, AZTEC allows for the reuse of previous preconditioning factorizations within Newton schemes for nonlinear methods. Currently, a number of different users are using this package to solve a variety of PDE applications.

  9. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Venneri, Mary Anna; Giannetta, Elisa; Panio, Giuseppe; De Gaetano, Rita; Gianfrilli, Daniele; Pofi, Riccardo; Masciarelli, Silvia; Fazi, Francesco; Pellegrini, Manuela; Lenzi, Andrea; Naro, Fabio; Isidori, Andrea M

    2015-01-01

    Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type) tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i) affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ)-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD) expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs), which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1) normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, PTEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like) to alternative (M2-like)/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent end-organ diabetic complications.

  10. Simulation of ODE/PDE models with MATLAB, OCTAVE and SCILAB scientific and engineering applications

    CERN Document Server

    Vande Wouwer, Alain; Vilas, Carlos

    2014-01-01

    Simulation of ODE/PDE Models with MATLAB®, OCTAVE and SCILAB shows the reader how to exploit a fuller array of numerical methods for the analysis of complex scientific and engineering systems than is conventionally employed. The book is dedicated to numerical simulation of distributed parameter systems described by mixed systems of algebraic equations, ordinary differential equations (ODEs) and partial differential equations (PDEs). Special attention is paid to the numerical method of lines (MOL), a popular approach to the solution of time-dependent PDEs, which proceeds in two basic steps: spatial discretization and time integration. Besides conventional finite-difference and -element techniques, more advanced spatial-approximation methods are examined in some detail, including nonoscillatory schemes and adaptive-grid approaches. A MOL toolbox has been developed within MATLAB®/OCTAVE/SCILAB. In addition to a set of spatial approximations and time integrators, this toolbox includes a collection of applicatio...

  11. Phosphodiesterase-9 (PDE9) inhibition with BAY 73-6691 increases corpus cavernosum relaxations mediated by nitric oxide-cyclic GMP pathway in mice.

    Science.gov (United States)

    da Silva, F H; Pereira, M N; Franco-Penteado, C F; De Nucci, G; Antunes, E; Claudino, M A

    2013-01-01

    Phosphodiesterase-9 (PDE9) specifically hydrolyzes cyclic GMP, and was detected in human corpus cavernosum. However, no previous studies explored the selective PDE9 inhibition with BAY 73-6691 in corpus cavernosum relaxations. Therefore, this study aimed to characterize the PDE9 mRNA expression in mice corpus cavernosum, and investigate the effects of BAY 73-6691 in endothelium-dependent and -independent relaxations, along with the nitrergic corpus cavernosum relaxations. Male mice received daily gavage of BAY 73-6691 (or dimethylsulfoxide) at 3 mg kg(-1) per day for 21 days. Relaxant responses to acetylcholine (ACh), nitric oxide (NO) (as acidified sodium nitrite; NaNO2 solution), sildenafil and electrical-field stimulation (EFS) were obtained in corpus cavernosum in control and BAY 73-6691-treated mice. BAY 73-6691 was also added in vitro 30 min before construction of concentration-responses and frequency curves. PDE9A and PDE5 mRNA expression was detected in the mice corpus cavernosum in a similar manner. In vitro addition of BAY 73-6691 neither itself relaxed mice corpus cavernosum nor changed the NaNO2, sildenafil and EFS-induced relaxations. However, in mice treated chronically with BAY 73-6691, the potency (pEC50) values for ACh, NaNO2 and sildenafil were significantly greater compared with control group. The maximal responses (Emax) to NaNO2 and sildenafil were also significantly greater in BAY 73-6691-treated mice. BAY 73-6691 treatment also significantly increased the magnitude and duration of the nitrergic corpus cavernosum relaxations (8-32 Hz). In conclusion, murine corpus cavernosum expresses PDE9 mRNA. Prolonged PDE9 inhibition with BAY 73-6691 amplifies the NO-cGMP-mediated cavernosal responses, and may be of therapeutic value for erectile dysfunction.

  12. Linear systems a measurement based approach

    CERN Document Server

    Bhattacharyya, S P; Mohsenizadeh, D N

    2014-01-01

    This brief presents recent results obtained on the analysis, synthesis and design of systems described by linear equations. It is well known that linear equations arise in most branches of science and engineering as well as social, biological and economic systems. The novelty of this approach is that no models of the system are assumed to be available, nor are they required. Instead, a few measurements made on the system can be processed strategically to directly extract design values that meet specifications without constructing a model of the system, implicitly or explicitly. These new concepts are illustrated by applying them to linear DC and AC circuits, mechanical, civil and hydraulic systems, signal flow block diagrams and control systems. These applications are preliminary and suggest many open problems. The results presented in this brief are the latest effort in this direction and the authors hope these will lead to attractive alternatives to model-based design of engineering and other systems.

  13. Discovery of novel PDE9 inhibitors capable of inhibiting Aβ aggregation as potential candidates for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Su, Tao; Zhang, Tianhua; Xie, Shishun; Yan, Jun; Wu, Yinuo; Li, Xingshu; Huang, Ling; Luo, Hai-Bin

    2016-02-01

    Recently, phosphodiesterase-9 (PDE9) inhibitors and biometal-chelators have received much attention as potential therapeutics for the treatment of Alzheimer’s disease (AD). Here, we designed, synthesized, and evaluated a novel series of PDE9 inhibitors with the ability to chelate metal ions. The bioassay results showed that most of these molecules strongly inhibited PDE9 activity. Compound 16 showed an IC50 of 34 nM against PDE9 and more than 55-fold selectivity against other PDEs. In addition, this compound displayed remarkable metal-chelating capacity and a considerable ability to halt copper redox cycling. Notably, in comparison to the reference compound clioquinol, it inhibited metal-induced Aβ1-42 aggregation more effectively and promoted greater disassembly of the highly structured Aβ fibrils generated through Cu2+-induced Aβ aggregation. These activities of 16, together with its favorable blood-brain barrier permeability, suggest that 16 may be a promising compound for treatment of AD.

  14. PDE-based geophysical modelling using finite elements: examples from 3D resistivity and 2D magnetotellurics

    International Nuclear Information System (INIS)

    Schaa, R; Gross, L; Du Plessis, J

    2016-01-01

    We present a general finite-element solver, escript, tailored to solve geophysical forward and inverse modeling problems in terms of partial differential equations (PDEs) with suitable boundary conditions. Escript’s abstract interface allows geoscientists to focus on solving the actual problem without being experts in numerical modeling. General-purpose finite element solvers have found wide use especially in engineering fields and find increasing application in the geophysical disciplines as these offer a single interface to tackle different geophysical problems. These solvers are useful for data interpretation and for research, but can also be a useful tool in educational settings. This paper serves as an introduction into PDE-based modeling with escript where we demonstrate in detail how escript is used to solve two different forward modeling problems from applied geophysics (3D DC resistivity and 2D magnetotellurics). Based on these two different cases, other geophysical modeling work can easily be realized. The escript package is implemented as a Python library and allows the solution of coupled, linear or non-linear, time-dependent PDEs. Parallel execution for both shared and distributed memory architectures is supported and can be used without modifications to the scripts. (paper)

  15. PDE-based geophysical modelling using finite elements: examples from 3D resistivity and 2D magnetotellurics

    Science.gov (United States)

    Schaa, R.; Gross, L.; du Plessis, J.

    2016-04-01

    We present a general finite-element solver, escript, tailored to solve geophysical forward and inverse modeling problems in terms of partial differential equations (PDEs) with suitable boundary conditions. Escript’s abstract interface allows geoscientists to focus on solving the actual problem without being experts in numerical modeling. General-purpose finite element solvers have found wide use especially in engineering fields and find increasing application in the geophysical disciplines as these offer a single interface to tackle different geophysical problems. These solvers are useful for data interpretation and for research, but can also be a useful tool in educational settings. This paper serves as an introduction into PDE-based modeling with escript where we demonstrate in detail how escript is used to solve two different forward modeling problems from applied geophysics (3D DC resistivity and 2D magnetotellurics). Based on these two different cases, other geophysical modeling work can easily be realized. The escript package is implemented as a Python library and allows the solution of coupled, linear or non-linear, time-dependent PDEs. Parallel execution for both shared and distributed memory architectures is supported and can be used without modifications to the scripts.

  16. Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples

    DEFF Research Database (Denmark)

    Kähler, Anna K; Otnæss, Mona K; Wirgenes, Katrine V

    2010-01-01

    The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect. We have genotyped......SNPs were nominally associated (0.0005 gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP...... were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs...

  17. Radiosynthesis and initial characterization of a PDE10A specific PET tracer [18 F]AMG 580 in non-human primates

    International Nuclear Information System (INIS)

    Hwang, Dah-Ren; Hu, Essa; Allen, Jennifer R.; Davis, Carl; Treanor, James; Miller, Silke; Chen, Hang; Shi, Bingzhi; Narayanan, Tanjorie K.; Barret, Olivier; Alagille, David; Yu, Zhigang; Slifstein, Mark

    2015-01-01

    Introduction: Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important second messengers for neurotransmission. Inhibition of PDE10A has been identified as a potential target for treatment of various neuropsychiatric disorders. To assist drug development, we have identified a selective PDE10A positron emission tomography (PET) tracer, AMG 580. We describe here the radiosynthesis of [ 18 F]AMG 580 and in vitro and in vivo characterization results. Methods: The potency and selectivity were determined by in vitro assay using [ 3 H]AMG 580 and baboon brain tissues. [ 18 F]AMG 580 was prepared by a 1-step [ 18 F]fluorination procedure. Dynamic brain PET scans were performed in non-human primates. Regions-of-interest were defined on individuals’ MRIs and transferred to the co-registered PET images. Data were analyzed using two tissue compartment analysis (2TC), Logan graphical (Logan) analysis with metabolite-corrected input function and the simplified reference tissue model (SRTM) method. A PDE10A inhibitor and unlabeled AMG 580 were used to demonstrate the PDE10A specificity. K D was estimated by Scatchard analysis of high and low affinity PET scans. Results: AMG 580 has an in vitro K D of 71.9 pM. Autoradiography showed specific uptake in striatum. Mean activity of 121 ± 18 MBq was used in PET studies. In Rhesus, the baseline BP ND for putamen and caudate was 3.38 and 2.34, respectively, via 2TC, and 3.16, 2.34 via Logan, and 2.92, and 2.01 via SRTM. A dose dependent decrease of BP ND was observed by the pre-treatment with a PDE10A inhibitor. In baboons, 0.24 mg/kg dose of AMG 580 resulted in about 70% decrease of BP ND . The in vivo K D of [ 18 F]AMG 580 was estimated to be around 0.44 nM in baboons. Conclusion: [ 18 F]AMG 580 is a selective and potent PDE10A PET tracer with excellent specific striatal binding in non-human primates. It warrants further evaluation in humans

  18. Compressor Surge Control Design Using Linear Matrix Inequality Approach

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2017-01-01

    A novel design for active compressor surge control system (ASCS) using linear matrix inequality (LMI) approach is presented and including a case study on piston-actuated active compressor surge control system (PAASCS). The non-linear system dynamics of the PAASCS is transformed into linear parameter varying (LPV) system dynamics. The system parameters are varying as a function of the compressor performance curve slope. A compressor surge stabilization problem is then formulated as a LMI probl...

  19. Alternate approaches to future electron-positron linear colliders

    International Nuclear Information System (INIS)

    Loew, G.A.

    1998-01-01

    The purpose of this article is two-fold: to review the current international status of various design approaches to the next generation of e + e - linear colliders, and on the occasion of his 80th birthday, to celebrate Richard B. Neal's many contributions to the field of linear accelerators. As it turns out, combining these two tasks is a rather natural enterprise because of Neal's long professional involvement and insight into many of the problems and options which the international e + e - linear collider community is currently studying to achieve a practical design for a future machine

  20. Repercussão cardiovascular, com e sem álcool, do carbonato de lodenafila, um novo inibidor da PDE5 Repercusión cardiovascular, con y sin alcohol, del carbonato de lodenafila, un nuevo inhibidor de la PDE5 Cardiovascular repercussion of lodenafil carbonate, a new PDE5 inhibitor, with and without alcohol consumption

    Directory of Open Access Journals (Sweden)

    Adauto Carvalho Silva

    2010-02-01

    Full Text Available FUNDAMENTO: A disfunção erétil afeta um grande número de homens no mundo e os inibidores de PDE 5 (iPDE5 estão entre os principais métodos de tratamento desses pacientes. O consumo social de álcool e o ato sexual apresentam uma relação considerável. Portanto, a associação entre álcool e iPDE5 pode ocorrer. O carbonato de lodenafila é um novo iPDE5 desenvolvido por uma empresa brasileira. OBJETIVO: Avaliar a repercussão cardiovascular do carbonato de lodenafila, associado ou não ao álcool, assim como as alterações na farmacocinética que esta associação possa determinar. MÉTODOS: Estudo realizado com 15 voluntários sadios que receberam em momentos diferentes o carbonato de lodenafila (CL na dose de 160 mg em jejum, CL (160 mg com álcool, ou somente placebo. Esses pacientes foram monitorados por 24 horas, sendo avaliado o quadro clínico, a pressão arterial (PA, a frequência cardíaca (FC, o intervalo QT e também os dados de farmacocinética. RESULTADOS: O carbonato de lodenafila, isoladamente ou associado com álcool, não determinou alterações clínicas significativas na PA ou FC, embora tenha ocorrido diminuição da PA estatisticamente significativa após 4 horas, nos voluntários que receberam medicamento e álcool, assim como um aumento da FC após 6 horas nos pacientes que receberam o CL. A análise do intervalo QT corrigido não mostrou alteração significativa. O álcool aumentou a biodisponibilidade do medicamento em 74%. Houve somente 2 queixas de cefaleia leve, possivelmente associada ao medicamento. CONCLUSÃO: O carbonato de lodenafila, mesmo associado ao álcool, não determinou repercussões clínicas importantes na PA, FC, ou alterações no intervalo QTc; a ingestão com álcool, por sua vez, aumentou significativamente sua biodisponibilidade.FUNDAMENTO: La disfunción eréctil afecta a un gran número de hombres en el mundo y los inhibidores de PDE5 (iPDE5 están entre los principales métodos de

  1. Exact solutions of linear reaction-diffusion processes on a uniformly growing domain: criteria for successful colonization.

    Science.gov (United States)

    Simpson, Matthew J

    2015-01-01

    Many processes during embryonic development involve transport and reaction of molecules, or transport and proliferation of cells, within growing tissues. Mathematical models of such processes usually take the form of a reaction-diffusion partial differential equation (PDE) on a growing domain. Previous analyses of such models have mainly involved solving the PDEs numerically. Here, we present a framework for calculating the exact solution of a linear reaction-diffusion PDE on a growing domain. We derive an exact solution for a general class of one-dimensional linear reaction-diffusion process on 0exact solutions with numerical approximations confirms the veracity of the method. Furthermore, our examples illustrate a delicate interplay between: (i) the rate at which the domain elongates, (ii) the diffusivity associated with the spreading density profile, (iii) the reaction rate, and (iv) the initial condition. Altering the balance between these four features leads to different outcomes in terms of whether an initial profile, located near x = 0, eventually overcomes the domain growth and colonizes the entire length of the domain by reaching the boundary where x = L(t).

  2. A BEHAVIORAL-APPROACH TO LINEAR EXACT MODELING

    NARCIS (Netherlands)

    ANTOULAS, AC; WILLEMS, JC

    1993-01-01

    The behavioral approach to system theory provides a parameter-free framework for the study of the general problem of linear exact modeling and recursive modeling. The main contribution of this paper is the solution of the (continuous-time) polynomial-exponential time series modeling problem. Both

  3. Pharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosum.

    Science.gov (United States)

    Toque, Haroldo A; Teixeira, Cleber E; Lorenzetti, Raquel; Okuyama, Cristina E; Antunes, Edson; De Nucci, Gilberto

    2008-09-04

    Nitrergic nerves and endothelial cells release nitric oxide (NO) in the corpus cavernosum, a key mediator that stimulates soluble guanylyl cyclase to increase cGMP levels causing penile erection. Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown. Here, we report a novel PDE5 inhibitor, lodenafil carbonate, (Bis-(2-{4-[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-benzenesulfonyl]piperazin-1-yl}-ethyl)carbonate) that is a dimer of lodenafil. We therefore aimed to compare the effects of sildenafil, lodenafil and lodenafil carbonate on in vitro human and rabbit cavernosal relaxations, activity of crude PDE extracts from human platelets, as well as stability and metabolic studies in rat, dog and human plasma. Pharmacokinetic evaluations after intravenous and oral administration were performed in male beagles. Functional experiments were conducted using organ bath techniques. Pharmacokinetics was studied in beagles by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), following oral or intravascular administration. All PDE5 inhibitors tested concentration-dependently relaxed (0.001-100 microM) phenylephrine-precontracted rabbit and human corpus cavernosum. The cavernosal relaxations evoked by either acetylcholine (0.01-100 microM) or electrical field stimulation (EFS, 1-20 Hz) were markedly potentiated by sildenafil, lodenafil and lodenafil carbonate. Lodenafil carbonate was more potent to inhibit the cGMP hydrolysis in PDE extracts compared with lodenafil and sildenafil. Following intravascular and single oral administration of lodenafil carbonate, only lodenafil and norlodenafil were detected in vivo. These results indicate that lodenafil carbonate works as a prodrug, being lodenafil the active moiety of lodenafil carbonate.

  4. Alternate approaches to future electron-positron linear colliders

    Energy Technology Data Exchange (ETDEWEB)

    Loew, G.A. [Stanford Univ., CA (United States). Stanford Linear Accelerator Center

    1998-07-01

    The purpose of this article is two-fold: to review the current international status of various design approaches to the next generation of e{sup +}e{sup {minus}} linear colliders, and on the occasion of his 80th birthday, to celebrate Richard B. Neal`s many contributions to the field of linear accelerators. As it turns out, combining these two tasks is a rather natural enterprise because of Neal`s long professional involvement and insight into many of the problems and options which the international e{sup +}e{sup {minus}} linear collider community is currently studying to achieve a practical design for a future machine.

  5. Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

    International Nuclear Information System (INIS)

    Fernández-Araujo, A.; Alfonso, A.; Vieytes, M.R.; Botana, L.M.

    2015-01-01

    Highlights: • YTX activates autophagic cell death after 48 h of treatment. • After 24 h of YTX incubation, the autophagic LC3B expression is increased. • High LC3B levels after 24 h can be related with extrinsic apoptosis activated by YTX. • PDEA4 plays a key role in the autophagy activation. - Abstract: Understanding the mechanism of action of the yessotoxin (YTX) is crucial since this drug has potential pharmacological effects in allergic processes, tumor proliferation and neurodegenerative diseases. It has been described that YTX activates apoptosis after 24 h of treatment, while after 48 h of incubation with the toxin a decrease in cell viability corresponding to cellular differentiation or non-apoptotic cell death was observed. In this paper, these processes were extensively studied by using the erythroleukemia K-562 cell line. On one hand, events of K-562 cell differentiation into erythrocytes after YTX treatment were studied using hemin as positive control of cell differentiation. Cell differentiation was studied through the cyclic nucleotide response element binding (phospho-CREB) and the transferrin receptor (TfR) expression. On the other hand, using rapamycin as positive control, autophagic hallmarks, as non-apoptotic cell death, were studied after toxin exposure. In this case, the mechanistic target of rapamycin (mTOR) and light chain 3B (LC3B) levels were measured to check autophagy activation. The results showed that cell differentiation was not occurring after 48 h of toxin incubation while at this time the autophagy was triggered. Furthermore after 24 h of toxin treatment none of these processes were activated. In addition, the role of the type 4A phosphodiesterase (PDE4A), the intracellular target of YTX, was checked. PDE4A-silencing experiments showed different regulation steps of PDE4A in the autophagic processes triggered either by traditional compounds or YTX. In summary, after 48 h YTX treatment PDE4A-dependent autophagy, as non

  6. A new method for extracting near-surface mass-density anomalies from land-based gravity data, based on a special case of Poisson's PDE at the Earth's surface: A case study of salt diapirs in the south of Iran

    Science.gov (United States)

    AllahTavakoli, Y.; Safari, A.; Ardalan, A.; Bahroudi, A.

    2015-12-01

    The current research provides a method for tracking near-surface mass-density anomalies via using only land-based gravity data, which is based on a special version of Poisson's Partial Differential Equation (PDE) of the gravitational field at Earth's surface. The research demonstrates how the Poisson's PDE can provide us with a capability to extract the near-surface mass-density anomalies from land-based gravity data. Herein, this version of the Poisson's PDE is mathematically introduced to the Earth's surface and then it is used to develop the new method for approximating the mass-density via derivatives of the Earth's gravitational field (i.e. via the gradient tensor). Herein, the author believes that the PDE can give us new knowledge about the behavior of the Earth's gravitational field at the Earth's surface which can be so useful for developing new methods of Earth's mass-density determination. In a case study, the proposed method is applied to a set of gravity stations located in the south of Iran. The results were numerically validated via certain knowledge about the geological structures in the area of the case study. Also, the method was compared with two standard methods of mass-density determination. All the numerical experiments show that the proposed approach is well-suited for tracking near-surface mass-density anomalies via using only the gravity data. Finally, the approach is also applied to some petroleum exploration studies of salt diapirs in the south of Iran.

  7. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors.

    Science.gov (United States)

    Kolontarev, Konstantin; Govorov, Alexander; Kasyan, George; Priymak, Diana; Pushkar, Dmitry

    2016-01-01

    Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors. The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed. Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected. The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

  8. Functions of PDE3 Isoforms in Cardiac Muscle

    Science.gov (United States)

    Movsesian, Matthew; Ahmad, Faiyaz

    2018-01-01

    Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the isoforms that have been identified in cardiac myocytes; the roles of these enzymes in modulating cAMP-mediated signalling and the processes mediated thereby; and the potential for targeting these enzymes to improve the profile of clinical responses. PMID:29415428

  9. The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with erectile dysfunction.

    Science.gov (United States)

    Fisher, William A; Rosen, Raymond C; Eardley, Ian; Niederberger, Craig; Nadel, Andrea; Kaufman, Joel; Sand, Michael

    2004-09-01

    The aim of Phase II of the Men's Attitudes to Life Events and Sexuality (MALES) Study is to explore PDE5 inhibitor treatment seeking among men with erectile dysfunction (ED). Phase II of the MALES study involved 2,912 men, aged 20-75 years, from 8 countries (U.S., U.K., Germany, France, Italy, Spain, Mexico, and Brazil), who reported ED. Participants were recruited from the MALES Phase I sample [1] and via booster methods (e.g., physician referral, street interception), and completed self-report questionnaires concerning the characteristics of their ED, their efforts to seek PDE5 inhibitor treatment for their sexual dysfunction, and attitudinal and referent influences that potentially affect treatment-seeking. Statistical analyses focus on identification of correlates of PDE5 inhibitor treatment seeking. PDE5 inhibitor utilization is strongly associated with ED sufferers' assessment of the severity of their sexual dysfunction, with their belief that medication for ED is dangerous, and with their perceptions of whether physicians, other professionals, and spouses or family members are supportive of their seeking treatment. ED sufferers who evaluate their sexual dysfunction as severe, who believe that medication for ED is not dangerous, and who perceive support for treatment seeking from referent others, are more likely to utilize PDE5 inhibitor treatment. Findings indicate that perceived ED severity, beliefs about ED medication, and referent influences are strongly correlated with utilization of PDE5 inhibitor therapy. These findings aid our understanding of factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy for their sexual dysfunction, and provide a basis for clinical and educational interventions to assist men with ED to seek appropriate treatment.

  10. Modulation of oxazolone-induced hypersensitivity in mice by selective PDE inhibitors

    Directory of Open Access Journals (Sweden)

    I. Moodley

    1995-01-01

    Full Text Available The effects of PDE inhibitors on oxazolone-induced contact hypersensitivity (CS were studied in mice. Rolipram, Ro 20-1724 and theophylline dose dependently inhibited CS but none caused >53% inhibition. ED30 values at 24 h before challenge for rolipram, Ro 20-1724 and theophylline were 2.1, 5.4 and 30.4 mg/kg, p.o., respectively. Milrinone and SKF 94836 at 30 mg/kg caused a small, but significant inhibition of 13% and 18%, respectively, although the inhibition (8% caused by zaprinast was not significant. Betamethasone (10 mg/kg, p.o. caused a marked inhibition (80% as did indomethacin (65% at 5 mg/kg, p.o.. Rolipram and Ro 20-1724 inhibited proliferation of mouse lymphoblasts with IC50 values of 0.08 μM and 0.83 μM, respectively. In contrast, zaprinast caused only a weak inhibition (IC50 = 119 μM of lymphocyte proliferation, whereas SKF 94836 and theophylline failed to cause any significant inhibition at 100 μM (26% and 2%, respectively. These findings suggest that PDE IV isozymes play a principal role in mediating CS by inhibiting lymphocyte activation.

  11. Comparison of preconditioned Krylov subspace iteration methods for PDE-constrained optimization problems

    Czech Academy of Sciences Publication Activity Database

    Axelsson, Owe; Farouq, S.; Neytcheva, M.

    2017-01-01

    Roč. 74, č. 1 (2017), s. 19-37 ISSN 1017-1398 Institutional support: RVO:68145535 Keywords : PDE-constrained optimization problems * finite elements * iterative solution methods * preconditioning Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.241, year: 2016 https://link.springer.com/article/10.1007%2Fs11075-016-0136-5

  12. PDE5 inhibitor treatment persistence and adherence in Brazilian men: post-hoc analyses from a 6-month, prospective, observational study.

    Science.gov (United States)

    Cairoli, Carlos; Reyes, Luis Antonio; Henneges, Carsten; Sorsaburu, Sebastian

    2014-01-01

    Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I) on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED). Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence/adherence. 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%). The prescribed PDE5I was sildenafil citrate for 50 (48.1%), tadalafil for 36 (34.6%), vardenafil for 15 (14.4%), and lodenafil for 3 patients (2.9%). Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0%) versus sildenafil or vardenafil (range 60.0% to 68.0%). Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment.

  13. PKA and PDE4D3 anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome

    Science.gov (United States)

    Terrin, Anna; Monterisi, Stefania; Stangherlin, Alessandra; Zoccarato, Anna; Koschinski, Andreas; Surdo, Nicoletta C.; Mongillo, Marco; Sawa, Akira; Jordanides, Niove E.; Mountford, Joanne C.

    2012-01-01

    Previous work has shown that the protein kinase A (PKA)–regulated phosphodiesterase (PDE) 4D3 binds to A kinase–anchoring proteins (AKAPs). One such protein, AKAP9, localizes to the centrosome. In this paper, we investigate whether a PKA–PDE4D3–AKAP9 complex can generate spatial compartmentalization of cyclic adenosine monophosphate (cAMP) signaling at the centrosome. Real-time imaging of fluorescence resonance energy transfer reporters shows that centrosomal PDE4D3 modulated a dynamic microdomain within which cAMP concentration selectively changed over the cell cycle. AKAP9-anchored, centrosomal PKA showed a reduced activation threshold as a consequence of increased autophosphorylation of its regulatory subunit at S114. Finally, disruption of the centrosomal cAMP microdomain by local displacement of PDE4D3 impaired cell cycle progression as a result of accumulation of cells in prophase. Our findings describe a novel mechanism of PKA activity regulation that relies on binding to AKAPs and consequent modulation of the enzyme activation threshold rather than on overall changes in cAMP levels. Further, we provide for the first time direct evidence that control of cell cycle progression relies on unique regulation of centrosomal cAMP/PKA signals. PMID:22908311

  14. PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signaling in cardiac myocytes.

    Science.gov (United States)

    Bedioune, Ibrahim; Lefebvre, Florence; Lechêne, Patrick; Varin, Audrey; Domergue, Valérie; Kapiloff, Michael S; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2018-05-03

    β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes. We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation. Both β1- and β2-AR stimulation increased cAMP and activated PKA in the cytoplasm. While the two receptors also increased cAMP in the nucleus, only β1-ARs increased nuclear PKA activity and up-regulated the PKA target gene and pro-apoptotic factor, inducible cAMP element repressor (ICER). Inhibition of PDE4, but not Gi, PDE3, GRK2 nor caveolae disruption disclosed nuclear PKA activation and ICER induction by β2-ARs. Both nuclear and cytoplasmic PKI prevented nuclear PKA activation and ICER induction by β1-ARs, indicating that PKA activation outside the nucleus is required for subsequent nuclear PKA activation and ICER mRNA expression. Cytoplasmic PKI also blocked ICER induction by β2-AR stimulation (with concomitant PDE4 inhibition). However, in this case nuclear PKI decreased ICER up-regulation by only 30%, indicating that other mechanisms are involved. Down-regulation of mAKAPβ partially inhibited nuclear PKA activation upon β1-AR stimulation, and drastically decreased nuclear PKA activation upon β2-AR stimulation in the presence of PDE4 inhibition. β1- and β2-ARs differentially regulate nuclear PKA activity and ICER expression in cardiomyocytes. PDE4 insulates a mAKAPβ-targeted PKA pool at the nuclear envelope that prevents nuclear PKA activation upon β2-AR stimulation.

  15. A 6 month, prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Latin American men with erectile dysfunction.

    Science.gov (United States)

    Rubio-Aurioles, Eusebio; Reyes, Luis Antonio; Borregales, Leonardo; Cairoli, Carlos; Sorsaburu, Sebastian

    2013-06-01

    To assess persistence/adherence rates of phosphodiesterase type-5 inhibitor (PDE5I) on-demand dosing in Latin American men with erectile dysfunction (ED), and explore patient characteristics and treatment factors that may be predictive for PDE5I persistence and adherence. Men from Brazil, Mexico, and Venezuela with ED who were naïve to PDE5Is were prescribed sildenafil, tadalafil, vardenafil, or lodenafil on-demand dosing and asked to provide information about PDE5I use at baseline and at 1, 3, and 6 months. Patients were persistent if they used ≥1 dose during the 4 week period prior to each evaluation. Patients were adherent if they complied with dosing instructions during most recent dose. Main outcome measures included Persistence and Adherence Questionnaire (PAQ), Partner Relationship Questionnaire (PRQ), Self-Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence and adherence. A total of 511 men were enrolled; most had mild to moderate ED (77.1%); 317 patients (62.0%) were prescribed tadalafil, 116 (22.7%) sildenafil, 75 (14.7%) vardenafil, and 3 (0.6%) lodenafil (not further analyzed). A total of 340 patients (66.5%) were 'persistent' at 6 months; 345 (67.5%) were 'adherent'. Persistence and adherence were associated with age, education level, and ED duration. Reasons for non-persistence included medication cost and lack of efficacy. Study limitations included its design, brief observation period, its bias observed toward tadalafil selection; its dependence on patient self-reporting, limited number of factors that were analyzed for persistence/adherence association, its small number of participating patients and Latin American countries, and inherent differences in PDE5I preference and medical practices. Approximately two-thirds of PDE5I-naïve, Latin American men with ED were persistent and adherent after 6 months of

  16. Non-linear Bayesian update of PCE coefficients

    KAUST Repository

    Litvinenko, Alexander

    2014-01-06

    Given: a physical system modeled by a PDE or ODE with uncertain coefficient q(?), a measurement operator Y (u(q), q), where u(q, ?) uncertain solution. Aim: to identify q(?). The mapping from parameters to observations is usually not invertible, hence this inverse identification problem is generally ill-posed. To identify q(!) we derived non-linear Bayesian update from the variational problem associated with conditional expectation. To reduce cost of the Bayesian update we offer a unctional approximation, e.g. polynomial chaos expansion (PCE). New: We apply Bayesian update to the PCE coefficients of the random coefficient q(?) (not to the probability density function of q).

  17. Non-linear Bayesian update of PCE coefficients

    KAUST Repository

    Litvinenko, Alexander; Matthies, Hermann G.; Pojonk, Oliver; Rosic, Bojana V.; Zander, Elmar

    2014-01-01

    Given: a physical system modeled by a PDE or ODE with uncertain coefficient q(?), a measurement operator Y (u(q), q), where u(q, ?) uncertain solution. Aim: to identify q(?). The mapping from parameters to observations is usually not invertible, hence this inverse identification problem is generally ill-posed. To identify q(!) we derived non-linear Bayesian update from the variational problem associated with conditional expectation. To reduce cost of the Bayesian update we offer a unctional approximation, e.g. polynomial chaos expansion (PCE). New: We apply Bayesian update to the PCE coefficients of the random coefficient q(?) (not to the probability density function of q).

  18. Comparison of preconditioned Krylov subspace iteration methods for PDE-constrained optimization problems

    Czech Academy of Sciences Publication Activity Database

    Axelsson, Owe; Farouq, S.; Neytcheva, M.

    2017-01-01

    Roč. 74, č. 1 (2017), s. 19-37 ISSN 1017-1398 Institutional support: RVO:68145535 Keywords : PDE-constrained optimization problems * finite elements * iterative solution method s * preconditioning Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.241, year: 2016 https://link.springer.com/article/10.1007%2Fs11075-016-0136-5

  19. Improved harmonic balance approach to periodic solutions of non-linear jerk equations

    International Nuclear Information System (INIS)

    Wu, B.S.; Lim, C.W.; Sun, W.P.

    2006-01-01

    An analytical approximate approach for determining periodic solutions of non-linear jerk equations involving third-order time-derivative is presented. This approach incorporates salient features of both Newton's method and the method of harmonic balance. By appropriately imposing the method of harmonic balance to the linearized equation, the approach requires only one or two iterations to predict very accurate analytical approximate solutions for a large range of initial velocity amplitude. One typical example is used to verify and illustrate the usefulness and effectiveness of the proposed approach

  20. A modified linear algebraic approach to electron scattering using cubic splines

    International Nuclear Information System (INIS)

    Kinney, R.A.

    1986-01-01

    A modified linear algebraic approach to the solution of the Schrodiner equation for low-energy electron scattering is presented. The method uses a piecewise cubic-spline approximation of the wavefunction. Results in the static-potential and the static-exchange approximations for e - +H s-wave scattering are compared with unmodified linear algebraic and variational linear algebraic methods. (author)

  1. Exact solutions of linear reaction-diffusion processes on a uniformly growing domain: criteria for successful colonization.

    Directory of Open Access Journals (Sweden)

    Matthew J Simpson

    Full Text Available Many processes during embryonic development involve transport and reaction of molecules, or transport and proliferation of cells, within growing tissues. Mathematical models of such processes usually take the form of a reaction-diffusion partial differential equation (PDE on a growing domain. Previous analyses of such models have mainly involved solving the PDEs numerically. Here, we present a framework for calculating the exact solution of a linear reaction-diffusion PDE on a growing domain. We derive an exact solution for a general class of one-dimensional linear reaction-diffusion process on 0

  2. A numerical investigation into the ability of the Poisson PDE to extract the mass-density from land-based gravity data: A case study of salt diapirs in the north coast of the Persian Gulf

    Science.gov (United States)

    AllahTavakoli, Yahya; Safari, Abdolreza

    2017-08-01

    This paper is counted as a numerical investigation into the capability of Poisson's Partial Differential Equation (PDE) at Earth's surface to extract the near-surface mass-density from land-based gravity data. For this purpose, first it focuses on approximating the gradient tensor of Earth's gravitational potential by means of land-based gravity data. Then, based on the concepts of both the gradient tensor and Poisson's PDE at the Earth's surface, certain formulae are proposed for the mass-density determination. Furthermore, this paper shows how the generalized Tikhonov regularization strategy can be used for enhancing the efficiency of the proposed approach. Finally, in a real case study, the formulae are applied to 6350 gravity stations located within a part of the north coast of the Persian Gulf. The case study numerically indicates that the proposed formulae, provided by Poisson's PDE, has the ability to convert land-based gravity data into the terrain mass-density which has been used for depicting areas of salt diapirs in the region of the case study.

  3. PDE5 Inhibitor Treatment Persistence and Adherence in Brazilian Men: Post-hoc Analyses from a 6-Month, Prospective, Observational Study

    Directory of Open Access Journals (Sweden)

    Carlos Cairoli

    2014-06-01

    Full Text Available Purpose Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED. Materials and Methods Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR Questionnaire, and International Index of Erectile Function (IIEF. Multivariate logistic regression was used to identify factors associated with persistence/adherence. Results 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%. The prescribed PDE5I was sildenafil citrate for 50 (48.1%, tadalafil for 36 (34.6%, vardenafil for 15 (14.4%, and lodenafil for 3 patients (2.9%. Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0% versus sildenafil or vardenafil (range 60.0% to 68.0%. Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Conclusion Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment.

  4. New approach to solve fully fuzzy system of linear equations using ...

    Indian Academy of Sciences (India)

    Known example problems are solved to illustrate the efficacy and ... The concept of fuzzy set and fuzzy number were first introduced by Zadeh .... (iii) Fully fuzzy linear systems can be solved by linear programming approach, Gauss elim-.

  5. Block-triangular preconditioners for PDE-constrained optimization

    KAUST Repository

    Rees, Tyrone

    2010-11-26

    In this paper we investigate the possibility of using a block-triangular preconditioner for saddle point problems arising in PDE-constrained optimization. In particular, we focus on a conjugate gradient-type method introduced by Bramble and Pasciak that uses self-adjointness of the preconditioned system in a non-standard inner product. We show when the Chebyshev semi-iteration is used as a preconditioner for the relevant matrix blocks involving the finite element mass matrix that the main drawback of the Bramble-Pasciak method-the appropriate scaling of the preconditioners-is easily overcome. We present an eigenvalue analysis for the block-triangular preconditioners that gives convergence bounds in the non-standard inner product and illustrates their competitiveness on a number of computed examples. Copyright © 2010 John Wiley & Sons, Ltd.

  6. Block-triangular preconditioners for PDE-constrained optimization

    KAUST Repository

    Rees, Tyrone; Stoll, Martin

    2010-01-01

    In this paper we investigate the possibility of using a block-triangular preconditioner for saddle point problems arising in PDE-constrained optimization. In particular, we focus on a conjugate gradient-type method introduced by Bramble and Pasciak that uses self-adjointness of the preconditioned system in a non-standard inner product. We show when the Chebyshev semi-iteration is used as a preconditioner for the relevant matrix blocks involving the finite element mass matrix that the main drawback of the Bramble-Pasciak method-the appropriate scaling of the preconditioners-is easily overcome. We present an eigenvalue analysis for the block-triangular preconditioners that gives convergence bounds in the non-standard inner product and illustrates their competitiveness on a number of computed examples. Copyright © 2010 John Wiley & Sons, Ltd.

  7. Analysis and implementation issues for the numerical approximation of parabolic equations with random coefficients

    KAUST Repository

    Nobile, Fabio; Tempone, Raul

    2009-01-01

    We consider the problem of numerically approximating statistical moments of the solution of a time- dependent linear parabolic partial differential equation (PDE), whose coefficients and/or forcing terms are spatially correlated random fields. The stochastic coefficients of the PDE are approximated by truncated Karhunen-Loève expansions driven by a finite number of uncorrelated random variables. After approxi- mating the stochastic coefficients, the original stochastic PDE turns into a new deterministic parametric PDE of the same type, the dimension of the parameter set being equal to the number of random variables introduced. After proving that the solution of the parametric PDE problem is analytic with respect to the parameters, we consider global polynomial approximations based on tensor product, total degree or sparse polynomial spaces and constructed by either a Stochastic Galerkin or a Stochastic Collocation approach. We derive convergence rates for the different cases and present numerical results that show how these approaches are a valid alternative to the more traditional Monte Carlo Method for this class of problems. © 2009 John Wiley & Sons, Ltd.

  8. Analysis and implementation issues for the numerical approximation of parabolic equations with random coefficients

    KAUST Repository

    Nobile, Fabio

    2009-11-05

    We consider the problem of numerically approximating statistical moments of the solution of a time- dependent linear parabolic partial differential equation (PDE), whose coefficients and/or forcing terms are spatially correlated random fields. The stochastic coefficients of the PDE are approximated by truncated Karhunen-Loève expansions driven by a finite number of uncorrelated random variables. After approxi- mating the stochastic coefficients, the original stochastic PDE turns into a new deterministic parametric PDE of the same type, the dimension of the parameter set being equal to the number of random variables introduced. After proving that the solution of the parametric PDE problem is analytic with respect to the parameters, we consider global polynomial approximations based on tensor product, total degree or sparse polynomial spaces and constructed by either a Stochastic Galerkin or a Stochastic Collocation approach. We derive convergence rates for the different cases and present numerical results that show how these approaches are a valid alternative to the more traditional Monte Carlo Method for this class of problems. © 2009 John Wiley & Sons, Ltd.

  9. A comparative study of reinitialization approaches of the level set method for simulating free-surface flows

    Energy Technology Data Exchange (ETDEWEB)

    Sufyan, Muhammad; Ngo, Long Cu; Choi, Hyoung Gwon [Seoul National University, Seoul (Korea, Republic of)

    2016-04-15

    Unstructured grids were used to compare the performance of a direct reinitialization scheme with those of two reinitialization approaches based on the solution of a hyperbolic Partial differential equation (PDE). The problems of moving interface were solved in the context of a finite element method. A least-square weighted residual method was used to discretize the advection equation of the level set method. The benchmark problems of rotating Zalesak's disk, time-reversed single vortex, and two-dimensional sloshing were examined. Numerical results showed that the direct reinitialization scheme performed better than the PDE-based reinitialization approaches in terms of mass conservation, dissipation and dispersion error, and computational time. In the case of sloshing, numerical results were found to be in good agreement with existing experimental data. The direct reinitialization approach consumed considerably less CPU time than the PDE-based simulations for 20 time periods of sloshing. This approach was stable, accurate, and efficient for all the problems considered in this study.

  10. Operator approach to linear control systems

    CERN Document Server

    Cheremensky, A

    1996-01-01

    Within the framework of the optimization problem for linear control systems with quadratic performance index (LQP), the operator approach allows the construction of a systems theory including a number of particular infinite-dimensional optimization problems with hardly visible concreteness. This approach yields interesting interpretations of these problems and more effective feedback design methods. This book is unique in its emphasis on developing methods for solving a sufficiently general LQP. Although this is complex material, the theory developed here is built on transparent and relatively simple principles, and readers with less experience in the field of operator theory will find enough material to give them a good overview of the current state of LQP theory and its applications. Audience: Graduate students and researchers in the fields of mathematical systems theory, operator theory, cybernetics, and control systems.

  11. [Cardiovascular repercussion of lodenafil carbonate, a new PDE5 inhibitor, with and without alcohol consumption].

    Science.gov (United States)

    Silva, Adauto Carvalho; Toffoletto, Odaly; Lucio, Luiz Antonio Galvão; Santos, Paula Ferreira Dos; Afiune, Jorge Barros; Massud Filho, João; Tufik, Sergio

    2010-02-01

    Millions of men around the world suffer from erectile dysfunction, for which phosphodiesterase 5 inhibitors (PDE-5 inhibitors) are currently the first treatment option. Sexual activity and alcohol consumption are closely related, and the simultaneous use of alcohol and PDE-5 inhibitors can happen. Lodenafil carbonate is a new PDE-5 inhibitor, developed by a Brazilian pharmaceutical company. This work aimed at evaluating the cardiovascular safety of lodenafil carbonate, with and without simultaneous alcohol consumption. Fifteen male volunteers received 160 mg lodenafil carbonate (LC), in three different moments. Participants were assigned to three groups, treated with LC in fasting condition, with alcohol or receiving only placebo. The volunteers were continuously monitored during 24 hours for physical impairment, blood pressure, heart rate, QT interval and lodenafil's pharmacokinetic parameters. Lodenafil carbonate alone or with alcohol did not induce clinically relevant modifications in arterial blood pressure or heart rate. A statistically significant decrease in blood pressure was seen four hours after LC and alcohol intake, and an increase in heart rate six hours after intake of lodenafil carbonate alone. The QTc interval was not significantly modified. Lodenafil carbonate bioavailability was increased in 74% when drug intake was associated with alcohol. These results show that the use of lodenafil carbonate did not have clinically relevant effects on blood pressure or heart rate, and was not associated with QT interval prolongation. The association of lodenafil carbonate and alcohol affected its pharmacokinetic properties, increasing the bioavailability of the drug.

  12. #DDOD Use Case: Access to Medicare Part D Drug Event File (PDE) for cost transparency

    Data.gov (United States)

    U.S. Department of Health & Human Services — SUMMARY DDOD use case to request access to Medicare Part D Drug Event File (PDE) for cost transparency to pharmacies and patients. WHAT IS A USE CASE? A “Use Case”...

  13. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

    Directory of Open Access Journals (Sweden)

    Marina ePolito

    2013-11-01

    Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

  14. Increase of Intracellular Cyclic AMP by PDE4 Inhibitors Affects HepG2 Cell Cycle Progression and Survival.

    Science.gov (United States)

    Massimi, Mara; Cardarelli, Silvia; Galli, Francesca; Giardi, Maria Federica; Ragusa, Federica; Panera, Nadia; Cinque, Benedetta; Cifone, Maria Grazia; Biagioni, Stefano; Giorgi, Mauro

    2017-06-01

    Type 4 cyclic nucleotide phosphodiesterases (PDE4) are major members of a superfamily of enzymes (PDE) involved in modulation of intracellular signaling mediated by cAMP. Broadly expressed in most human tissues and present in large amounts in the liver, PDEs have in the last decade been key therapeutic targets for several inflammatory diseases. Recently, a significant body of work has underscored their involvement in different kinds of cancer, but with no attention paid to liver cancer. The present study investigated the effects of two PDE4 inhibitors, rolipram and DC-TA-46, on the growth of human hepatoma HepG2 cells. Treatment with these inhibitors caused a marked increase of intracellular cAMP level and a dose- and time-dependent effect on cell growth. The concentrations of inhibitors that halved cell proliferation to about 50% were used for cell cycle experiments. Rolipram (10 μM) and DC-TA-46 (0.5 μM) produced a decrease of cyclin expression, in particular of cyclin A, as well as an increase in p21, p27 and p53, as evaluated by Western blot analysis. Changes in the intracellular localization of cyclin D1 were also observed after treatments. In addition, both inhibitors caused apoptosis, as demonstrated by an Annexin-V cytofluorimetric assay and analysis of caspase-3/7 activity. Results demonstrated that treatment with PDE4 inhibitors affected HepG2 cell cycle and survival, suggesting that they might be useful as potential adjuvant, chemotherapeutic or chemopreventive agents in hepatocellular carcinoma. J. Cell. Biochem. 118: 1401-1411, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Adaptive observer for the joint estimation of parameters and input for a coupled wave PDE and infinite dimensional ODE system

    KAUST Repository

    Belkhatir, Zehor

    2016-08-05

    This paper deals with joint parameters and input estimation for coupled PDE-ODE system. The system consists of a damped wave equation and an infinite dimensional ODE. This model describes the spatiotemporal hemodynamic response in the brain and the objective is to characterize brain regions using functional Magnetic Resonance Imaging (fMRI) data. For this reason, we propose an adaptive estimator and prove the asymptotic convergence of the state, the unknown input and the unknown parameters. The proof is based on a Lyapunov approach combined with a priori identifiability assumptions. The performance of the proposed observer is illustrated through some simulation results.

  16. Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    2007-01-01

    Full Text Available A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA. Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4 inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

  17. Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

    Science.gov (United States)

    Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

    2007-01-01

    A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

  18. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice.

    Directory of Open Access Journals (Sweden)

    Mary Anna Venneri

    Full Text Available Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs, which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1 normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, P<0.01; 2 prevents STZ-induced tissue inflammatory infiltration (4-fold increase in F4/80+ macrophages in diabetic vs. control mice by increasing renal and heart anti-inflammatory TEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P <0.01, and 11.6 ± 2.9% in CTRL mice; 3 reduces vascular inflammatory proteins (iNOS, COX2, VCAM-1 promoting tissue protection; 4 lowers monocyte adhesion to human endothelial cells in vitro through the TIE2 receptor. All these changes occurred independently from changes of glycemic status. In summary, we demonstrate that circulating renal and cardiac TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like to alternative (M2-like/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent

  19. Simple Planar Truss (Linear, Nonlinear and Stochastic Approach

    Directory of Open Access Journals (Sweden)

    Frydrýšek Karel

    2016-11-01

    Full Text Available This article deals with a simple planar and statically determinate pin-connected truss. It demonstrates the processes and methods of derivations and solutions according to 1st and 2nd order theories. The article applies linear and nonlinear approaches and their simplifications via a Maclaurin series. Programming connected with the stochastic Simulation-Based Reliability Method (i.e. the direct Monte Carlo approach is used to conduct a probabilistic reliability assessment (i.e. a calculation of the probability that plastic deformation will occur in members of the truss.

  20. A convex optimization approach for solving large scale linear systems

    Directory of Open Access Journals (Sweden)

    Debora Cores

    2017-01-01

    Full Text Available The well-known Conjugate Gradient (CG method minimizes a strictly convex quadratic function for solving large-scale linear system of equations when the coefficient matrix is symmetric and positive definite. In this work we present and analyze a non-quadratic convex function for solving any large-scale linear system of equations regardless of the characteristics of the coefficient matrix. For finding the global minimizers, of this new convex function, any low-cost iterative optimization technique could be applied. In particular, we propose to use the low-cost globally convergent Spectral Projected Gradient (SPG method, which allow us to extend this optimization approach for solving consistent square and rectangular linear system, as well as linear feasibility problem, with and without convex constraints and with and without preconditioning strategies. Our numerical results indicate that the new scheme outperforms state-of-the-art iterative techniques for solving linear systems when the symmetric part of the coefficient matrix is indefinite, and also for solving linear feasibility problems.

  1. Linear decomposition approach for a class of nonconvex programming problems.

    Science.gov (United States)

    Shen, Peiping; Wang, Chunfeng

    2017-01-01

    This paper presents a linear decomposition approach for a class of nonconvex programming problems by dividing the input space into polynomially many grids. It shows that under certain assumptions the original problem can be transformed and decomposed into a polynomial number of equivalent linear programming subproblems. Based on solving a series of liner programming subproblems corresponding to those grid points we can obtain the near-optimal solution of the original problem. Compared to existing results in the literature, the proposed algorithm does not require the assumptions of quasi-concavity and differentiability of the objective function, and it differs significantly giving an interesting approach to solving the problem with a reduced running time.

  2. Memristance controlling approach based on modification of linear M—q curve

    International Nuclear Information System (INIS)

    Liu Hai-Jun; Li Zhi-Wei; Yu Hong-Qi; Sun Zhao-Lin; Nie Hong-Shan

    2014-01-01

    The memristor has broad application prospects in many fields, while in many cases, those fields require accurate impedance control. The nonlinear model is of great importance for realizing memristance control accurately, but the implementing complexity caused by iteration has limited the actual application of this model. Considering the approximate linear characteristics at the middle region of the memristance-charge (M—q) curve of the nonlinear model, this paper proposes a memristance controlling approach, which is achieved by linearizing the middle region of the M—q curve of the nonlinear memristor, and establishes the linear relationship between memristances M and input excitations so that it can realize impedance control precisely by only adjusting input signals briefly. First, it analyzes the feasibility for linearizing the middle part of the M—q curve of the memristor with a nonlinear model from the qualitative perspective. Then, the linearization equations of the middle region of the M—q curve is constructed by using the shift method, and under a sinusoidal excitation case, the analytical relation between the memristance M and the charge time t is derived through the Taylor series expansions. At last, the performance of the proposed approach is demonstrated, including the linearizing capability for the middle part of the M—q curve of the nonlinear model memristor, the controlling ability for memristance M, and the influence of input excitation on linearization errors. (interdisciplinary physics and related areas of science and technology)

  3. Essential linear algebra with applications a problem-solving approach

    CERN Document Server

    Andreescu, Titu

    2014-01-01

    This textbook provides a rigorous introduction to linear algebra in addition to material suitable for a more advanced course while emphasizing the subject’s interactions with other topics in mathematics such as calculus and geometry. A problem-based approach is used to develop the theoretical foundations of vector spaces, linear equations, matrix algebra, eigenvectors, and orthogonality. Key features include: • a thorough presentation of the main results in linear algebra along with numerous examples to illustrate the theory;  • over 500 problems (half with complete solutions) carefully selected for their elegance and theoretical significance; • an interleaved discussion of geometry and linear algebra, giving readers a solid understanding of both topics and the relationship between them.   Numerous exercises and well-chosen examples make this text suitable for advanced courses at the junior or senior levels. It can also serve as a source of supplementary problems for a sophomore-level course.    ...

  4. Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate

    NARCIS (Netherlands)

    Uckert, Stefan; Oelke, Matthias; Stief, Christian G.; Andersson, K.-E.; Jonas, Udo; Hedlund, Petter

    2006-01-01

    With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate.

  5. Output Feedback-Based Boundary Control of Uncertain Coupled Semilinear Parabolic PDE Using Neurodynamic Programming.

    Science.gov (United States)

    Talaei, Behzad; Jagannathan, Sarangapani; Singler, John

    2018-04-01

    In this paper, neurodynamic programming-based output feedback boundary control of distributed parameter systems governed by uncertain coupled semilinear parabolic partial differential equations (PDEs) under Neumann or Dirichlet boundary control conditions is introduced. First, Hamilton-Jacobi-Bellman (HJB) equation is formulated in the original PDE domain and the optimal control policy is derived using the value functional as the solution of the HJB equation. Subsequently, a novel observer is developed to estimate the system states given the uncertain nonlinearity in PDE dynamics and measured outputs. Consequently, the suboptimal boundary control policy is obtained by forward-in-time estimation of the value functional using a neural network (NN)-based online approximator and estimated state vector obtained from the NN observer. Novel adaptive tuning laws in continuous time are proposed for learning the value functional online to satisfy the HJB equation along system trajectories while ensuring the closed-loop stability. Local uniformly ultimate boundedness of the closed-loop system is verified by using Lyapunov theory. The performance of the proposed controller is verified via simulation on an unstable coupled diffusion reaction process.

  6. Parallel linear solvers for simulations of reactor thermal hydraulics

    International Nuclear Information System (INIS)

    Yan, Y.; Antal, S.P.; Edge, B.; Keyes, D.E.; Shaver, D.; Bolotnov, I.A.; Podowski, M.Z.

    2011-01-01

    The state-of-the-art multiphase fluid dynamics code, NPHASE-CMFD, performs multiphase flow simulations in complex domains using implicit nonlinear treatment of the governing equations and in parallel, which is a very challenging environment for the linear solver. The present work illustrates how the Portable, Extensible Toolkit for Scientific Computation (PETSc) and scalable Algebraic Multigrid (AMG) preconditioner from Hypre can be utilized to construct robust and scalable linear solvers for the Newton correction equation obtained from the discretized system of governing conservation equations in NPHASE-CMFD. The overall long-tem objective of this work is to extend the NPHASE-CMFD code into a fully-scalable solver of multiphase flow and heat transfer problems, applicable to both steady-state and stiff time-dependent phenomena in complete fuel assemblies of nuclear reactors and, eventually, the entire reactor core (such as the Virtual Reactor concept envisioned by CASL). This campaign appropriately begins with the linear algebraic equation solver, which is traditionally a bottleneck to scalability in PDE-based codes. The computational complexity of the solver is usually superlinear in problem size, whereas the rest of the code, the “physics” portion, usually has its complexity linear in the problem size. (author)

  7. Two-scale approach to oscillatory singularly perturbed transport equations

    CERN Document Server

    Frénod, Emmanuel

    2017-01-01

    This book presents the classical results of the two-scale convergence theory and explains – using several figures – why it works. It then shows how to use this theory to homogenize ordinary differential equations with oscillating coefficients as well as oscillatory singularly perturbed ordinary differential equations. In addition, it explores the homogenization of hyperbolic partial differential equations with oscillating coefficients and linear oscillatory singularly perturbed hyperbolic partial differential equations. Further, it introduces readers to the two-scale numerical methods that can be built from the previous approaches to solve oscillatory singularly perturbed transport equations (ODE and hyperbolic PDE) and demonstrates how they can be used efficiently. This book appeals to master’s and PhD students interested in homogenization and numerics, as well as to the Iter community.

  8. Homology modeling, docking studies and molecular dynamic simulations using graphical processing unit architecture to probe the type-11 phosphodiesterase catalytic site: a computational approach for the rational design of selective inhibitors.

    Science.gov (United States)

    Cichero, Elena; D'Ursi, Pasqualina; Moscatelli, Marco; Bruno, Olga; Orro, Alessandro; Rotolo, Chiara; Milanesi, Luciano; Fossa, Paola

    2013-12-01

    Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be identified, acting on both cyclic adenosine monophosphate and cyclic guanosine monophosphate. The initial reports of PDE11 found evidence for PDE11 expression in skeletal muscle, prostate, testis, and salivary glands; however, the tissue distribution of PDE11 still remains a topic of active study and some controversy. Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors have been shown to cross-react with PDE11. Accordingly, many non-selective inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2-d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11 isoform. In the absence of experimental data about PDE11 X-ray structures, we found interesting to gain a better understanding of the enzyme-inhibitor interactions using in silico simulations. In this work, we describe a computational approach based on homology modeling, docking, and molecular dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical Processing Unit architecture, it is possible to perform long simulations, find stable interactions involved in the complex, and finally to suggest guideline for the identification and synthesis of potent and selective inhibitors. © 2013 John Wiley & Sons A/S.

  9. The PDE10A inhibitor MP-10 and haloperidol produce distinct gene expression profiles in the striatum and influence cataleptic behavior in rodents.

    Science.gov (United States)

    Gentzel, Renee C; Toolan, Dawn; Roberts, Rhonda; Koser, Amy Jo; Kandebo, Monika; Hershey, James; Renger, John J; Uslaner, Jason; Smith, Sean M

    2015-12-01

    Phosphodiesterase 10A (PDE10A) has garnered attention as a potential therapeutic target for schizophrenia due to its prominent striatal expression and ability to modulate striatal signaling. The present study used the selective PDE10A inhibitor MP-10 and the dopamine D2 antagonist haloperidol to compare effects of PDE10A inhibition and dopamine D2 blockade on striatopallidal (D2) and striatonigral (D1) pathway activation. Our studies confirmed that administration of MP-10 significantly elevates expression of the immediate early genes (IEG) c-fos, egr-1, and arc in rat striatum. Furthermore, we demonstrated that MP-10 induced egr-1 expression was distributed evenly between enkephalin-containing D2-neurons and substance P-containing D1-neurons. In contrast, haloperidol (3 mg/kg) selectively activated egr-1 expression in enkephalin neurons. Co-administration of MP-10 and haloperidol (0.5 mg/kg) increased IEG expression to a greater extent than either compound alone. Similarly, in a rat catalepsy assay, administration of haloperidol (0.5 mg/kg) or MP-10 (3-30 mg/kg) did not produce cataleptic behavior when dosed alone, but co-administration of haloperidol with MP-10 (3 and 10 mg/kg) induced cataleptic behaviors. Interestingly, co-administration of haloperidol with a high dose of MP-10 (30 mg/kg) failed to produce cataleptic behavior. These findings are important for understanding the neural circuits involved in catalepsy and suggest that the behavioral effects produced by PDE10A inhibitors may be influenced by concomitant medication and the level of PDE10A inhibition achieved by the dose of the inhibitor. Copyright © 2015. Published by Elsevier Ltd.

  10. New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment.

    Science.gov (United States)

    Brullo, Chiara; Ricciarelli, Roberta; Prickaerts, Jos; Arancio, Ottavio; Massa, Matteo; Rotolo, Chiara; Romussi, Alessia; Rebosio, Claudia; Marengo, Barbara; Pronzato, Maria Adelaide; van Hagen, Britt T J; van Goethem, Nick P; D'Ursi, Pasqualina; Orro, Alessandro; Milanesi, Luciano; Guariento, Sara; Cichero, Elena; Fossa, Paola; Fedele, Ernesto; Bruno, Olga

    2016-11-29

    Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. A non-linear programming approach to the computer-aided design of regulators using a linear-quadratic formulation

    Science.gov (United States)

    Fleming, P.

    1985-01-01

    A design technique is proposed for linear regulators in which a feedback controller of fixed structure is chosen to minimize an integral quadratic objective function subject to the satisfaction of integral quadratic constraint functions. Application of a non-linear programming algorithm to this mathematically tractable formulation results in an efficient and useful computer-aided design tool. Particular attention is paid to computational efficiency and various recommendations are made. Two design examples illustrate the flexibility of the approach and highlight the special insight afforded to the designer.

  12. A Compensatory Approach to Multiobjective Linear Transportation Problem with Fuzzy Cost Coefficients

    Directory of Open Access Journals (Sweden)

    Hale Gonce Kocken

    2011-01-01

    Full Text Available This paper deals with the Multiobjective Linear Transportation Problem that has fuzzy cost coefficients. In the solution procedure, many objectives may conflict with each other; therefore decision-making process becomes complicated. And also due to the fuzziness in the costs, this problem has a nonlinear structure. In this paper, fuzziness in the objective functions is handled with a fuzzy programming technique in the sense of multiobjective approach. And then we present a compensatory approach to solve Multiobjective Linear Transportation Problem with fuzzy cost coefficients by using Werner's and operator. Our approach generates compromise solutions which are both compensatory and Pareto optimal. A numerical example has been provided to illustrate the problem.

  13. Linear-algebraic approach to electron-molecule collisions: General formulation

    International Nuclear Information System (INIS)

    Collins, L.A.; Schneider, B.I.

    1981-01-01

    We present a linear-algebraic approach to electron-molecule collisions based on an integral equations form with either logarithmic or asymptotic boundary conditions. The introduction of exchange effects does not alter the basic form or order of the linear-algebraic equations for a local potential. In addition to the standard procedure of directly evaluating the exchange integrals by numerical quadrature, we also incorporate exchange effects through a separable-potential approximation. Efficient schemes are developed for reducing the number of points and channels that must be included. The method is applied at the static-exchange level to a number of molecular systems including H 2 , N 2 , LiH, and CO 2

  14. Optimality conditions for the numerical solution of optimization problems with PDE constraints :

    Energy Technology Data Exchange (ETDEWEB)

    Aguilo Valentin, Miguel Alejandro; Ridzal, Denis

    2014-03-01

    A theoretical framework for the numerical solution of partial di erential equation (PDE) constrained optimization problems is presented in this report. This theoretical framework embodies the fundamental infrastructure required to e ciently implement and solve this class of problems. Detail derivations of the optimality conditions required to accurately solve several parameter identi cation and optimal control problems are also provided in this report. This will allow the reader to further understand how the theoretical abstraction presented in this report translates to the application.

  15. Hyperprolactinemia contributes to reproductive deficit in male rats chronically administered PDE5 inhibitors (sildenafil and tadalafil and opioid (tramadol

    Directory of Open Access Journals (Sweden)

    V.U. Nna

    2016-09-01

    Conclusion: Serum prolactin concentration correlated negatively with male reproductive hormones and may play a major role in reproductive deficits associated with chronic use of PDE5 inhibitors and opioids.

  16. An Elliptic PDE Approach for Shape Characterization

    Science.gov (United States)

    Haidar, Haissam; Bouix, Sylvain; Levitt, James; McCarley, Robert W.; Shenton, Martha E.; Soul, Janet S.

    2009-01-01

    This paper presents a novel approach to analyze the shape of anatomical structures. Our methodology is rooted in classical physics and in particular Poisson's equation, a fundamental partial differential equation [1]. The solution to this equation and more specifically its equipotential surfaces display properties that are useful for shape analysis. We present a numerical algorithm to calculate the length of streamlines formed by the gradient field of the solution to this equation for 2D and 3D objects. The length of the streamlines along the equipotential surfaces was used to build a new function which can characterize the shape of objects. We illustrate our method on 2D synthetic and natural shapes as well as 3D medical data. PMID:17271986

  17. Decision tree analyses of key patient characteristics in Middle Eastern/North African and Latin American men treated with long-acting and short-acting PDE5 inhibitors for erectile dysfunction.

    Science.gov (United States)

    Rubio-Aurioles, Eusebio; El-Meliegy, Amr; Abdulwahed, Samer; Henneges, Carsten; Sorsaburu, Sebastian; Gurbuz, Sirel

    2015-02-01

    Phosphodiesterase type 5 (PDE5) inhibitors have discontinuation rates as high as 60% in men with erectile dysfunction. Treatment satisfaction has been significantly associated with treatment continuation. Understanding key characteristics in terms of treatment preference, relationship, and lifestyle issues could provide direction on how to improve compliance with PDE5 inhibitor treatment globally. The objective was to identify subgroups of interest in the pooled database of two observational studies conducted in Latin America (LA) and Middle East/North Africa (MENA) exploring patient characteristics and prescription of either a long- or short-acting PDE5 inhibitor at baseline. Two identical prospective, non-interventional, observational, studies in MENA (N = 493) and LA (N = 511) treated men with an 'on demand' (pro re nata, PRN) PDE5 inhibitor (sildenafil, tadalafil, vardenafil, or lodenafil) during 6 months. In this post-hoc meta-analysis of two observational studies with equal design, pooled data were analyzed to determine patient characteristics and PDE5 inhibitor prescribed/used most likely to be associated with patient expectations, satisfaction, self-esteem, and patient-partner relationships. Decision tree analyses, with and without weighting, were used to identify and describe key features. In each analysis of patient expectations, patient-partner relationship, and self-esteem, we describe the two major subgroups at baseline for each decision tree. Analyses of patient expectations and sexual self-esteem revealed that patients prescribed long-acting PDE5 inhibitors (59%) highlighted the importance of treatment effect duration, second to partner satisfaction with treatment, while patients prescribed short-acting PDE5 inhibitors (32%) placed less importance on treatment effect duration but considerable importance on treatment effect lasting until intercourse completion. Further insights regarding patients, partner relationship characteristics, and

  18. Development of two fluorine-18 labeled PET radioligands targeting PDE10A and in vivo PET evaluation in nonhuman primates.

    Science.gov (United States)

    Stepanov, Vladimir; Takano, Akihiro; Nakao, Ryuji; Amini, Nahid; Miura, Shotaro; Hasui, Tomoaki; Kimura, Haruhide; Taniguchi, Takahiko; Halldin, Christer

    2018-02-01

    Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [ 11 C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [ 11 C]T-773. [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were synthesized from the same precursor used for 11 C-labeling of T-773 in a two-step approach via 18 F-fluoromethylation and 18 F-fluoroethylation, respectively, using corresponding deuterated synthons. A total of 12 PET measurements were performed in seven non-human primates. First, baseline PET measurements were performed using High Resolution Research Tomograph system with both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 ; the uptake in whole brain and separate brain regions, as well as the specific binding and tissue ratio between putamen and cerebellum, was examined. Second, baseline and pretreatment PET measurements using MP-10 as the blocker were performed for [ 18 F]FM-T-773-d 2 including arterial blood sampling with radiometabolite analysis in four NHPs. Both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were successfully radiolabeled with an average molar activity of 293 ± 114 GBq/μmol (n=8) for [ 18 F]FM-T-773-d 2 and 209 ± 26 GBq/μmol (n=4) for [ 18 F]FE-T-773-d 4 , and a radiochemical yield of 10% (EOB, n=12, range 3%-16%). Both radioligands displayed high brain uptake (~5.5% of injected radioactivity for [ 18 F]FM-T-773-d 2 and ~3.5% for [ 18 F]FE-T-773-d 4 at the peak) and a fast washout. Specific binding reached maximum within 30 min for [ 18 F]FM-T-773-d 2 and after approximately 45 min for [ 18 F]FE-T-773-d 4 . [ 18 F]FM-T-773-d 2 data fitted well with kinetic compartment models. BP ND values obtained indirectly through compartment models were correlated well with those obtained by SRTM. BP ND calculated with SRTM was 1.0-1.7 in the putamen. The occupancy with 1

  19. On the deflagration-to-detonation transition (DDT) process with added energetic solid particles for pulse detonation engines (PDE)

    Science.gov (United States)

    Nguyen, V. B.; Li, J.; Chang, P.-H.; Phan, Q. T.; Teo, C. J.; Khoo, B. C.

    2018-01-01

    In this paper, numerical simulations are performed to study the dynamics of the deflagration-to-detonation transition (DDT) in pulse detonation engines (PDE) using energetic aluminum particles. The DDT process and detonation wave propagation toward the unburnt hydrogen/air mixture containing solid aluminum particles is numerically studied using the Eulerian-Lagrangian approach. A hybrid numerical methodology combined with appropriate sub-models is used to capture the gas dynamic characteristics, particle behavior, combustion characteristics, and two-way solid-particle-gas flow interactions. In our approach, the gas mixture is expressed in the Eulerian frame of reference, while the solid aluminum particles are tracked in the Lagrangian frame of reference. The implemented computer code is validated using published benchmark problems. The obtained results show that the aluminum particles not only shorten the DDT length but also reduce the DDT time. The improvement of DDT is primarily attributed to the heat released from surface chemical reactions on the aluminum particles. The temperatures associated with the DDT process are greater than the case of non-reacting particles added, with an accompanying rise in the pressure. For an appropriate range of particle volume fraction, particularly in this study, the higher volume fraction of the micro-aluminum particles added in the detonation chamber can lead to more heat energy released and more local instabilities in the combustion process (caused by the local high temperature), thereby resulting in a faster DDT process. In essence, the aluminum particles contribute to the DDT process of successfully transitioning to detonation waves for (failure) cases in which the fuel gas mixture can be either too lean or too rich. With a better understanding of the influence of added aluminum particles on the dynamics of the DDT and detonation process, we can apply it to modify the geometry of the detonation chamber (e.g., the length of

  20. Review of the superconducting approach to linear colliders

    International Nuclear Information System (INIS)

    Padamsee, H.

    1992-01-01

    For the next linear collider of 500 GeV CM energy, the beam energy needs to be increased by a factor of 5 over the SLC, but the luminosity needs to be increased by 5 orders of magnitude. The superconducting (SRF) approach offers multiple relief from the many pressing challenges of achieving high luminosity. The major challenges for the SRF approach are to raise the gradients well above 5 MV/m possible today and at the same time to lower the costs. Progress in SRF technology is presented. A collaborative venture on a TESLA TEST FACILITY is now taking shape, these activities are summarized. (R.P.) 19 refs.; 4 figs.; 3 tabs

  1. Alternating Direction Implicit (ADI) schemes for a PDE-based image osmosis model

    Science.gov (United States)

    Calatroni, L.; Estatico, C.; Garibaldi, N.; Parisotto, S.

    2017-10-01

    We consider Alternating Direction Implicit (ADI) splitting schemes to compute efficiently the numerical solution of the PDE osmosis model considered by Weickert et al. in [10] for several imaging applications. The discretised scheme is shown to preserve analogous properties to the continuous model. The dimensional splitting strategy traduces numerically into the solution of simple tridiagonal systems for which standard matrix factorisation techniques can be used to improve upon the performance of classical implicit methods, even for large time steps. Applications to the shadow removal problem are presented.

  2. Applications of equivalent linearization approaches to nonlinear piping systems

    International Nuclear Information System (INIS)

    Park, Y.; Hofmayer, C.; Chokshi, N.

    1997-01-01

    The piping systems in nuclear power plants, even with conventional snubber supports, are highly complex nonlinear structures under severe earthquake loadings mainly due to various mechanical gaps in support structures. Some type of nonlinear analysis is necessary to accurately predict the piping responses under earthquake loadings. The application of equivalent linearization approaches (ELA) to seismic analyses of nonlinear piping systems is presented. Two types of ELA's are studied; i.e., one based on the response spectrum method and the other based on the linear random vibration theory. The test results of main steam and feedwater piping systems supported by snubbers and energy absorbers are used to evaluate the numerical accuracy and limitations

  3. Fast Multipole-Based Elliptic PDE Solver and Preconditioner

    KAUST Repository

    Ibeid, Huda

    2016-12-07

    Exascale systems are predicted to have approximately one billion cores, assuming Gigahertz cores. Limitations on affordable network topologies for distributed memory systems of such massive scale bring new challenges to the currently dominant parallel programing model. Currently, there are many efforts to evaluate the hardware and software bottlenecks of exascale designs. It is therefore of interest to model application performance and to understand what changes need to be made to ensure extrapolated scalability. Fast multipole methods (FMM) were originally developed for accelerating N-body problems for particle-based methods in astrophysics and molecular dynamics. FMM is more than an N-body solver, however. Recent efforts to view the FMM as an elliptic PDE solver have opened the possibility to use it as a preconditioner for even a broader range of applications. In this thesis, we (i) discuss the challenges for FMM on current parallel computers and future exascale architectures, with a focus on inter-node communication, and develop a performance model that considers the communication patterns of the FMM for spatially quasi-uniform distributions, (ii) employ this performance model to guide performance and scaling improvement of FMM for all-atom molecular dynamics simulations of uniformly distributed particles, and (iii) demonstrate that, beyond its traditional use as a solver in problems for which explicit free-space kernel representations are available, the FMM has applicability as a preconditioner in finite domain elliptic boundary value problems, by equipping it with boundary integral capability for satisfying conditions at finite boundaries and by wrapping it in a Krylov method for extensibility to more general operators. Compared with multilevel methods, FMM is capable of comparable algebraic convergence rates down to the truncation error of the discretized PDE, and it has superior multicore and distributed memory scalability properties on commodity

  4. A homotopy analysis method for the option pricing PDE in illiquid markets

    Science.gov (United States)

    E-Khatib, Youssef

    2012-09-01

    One of the shortcomings of the Black and Scholes model on option pricing is the assumption that trading the underlying asset does not affect the underlying asset price. This can happen in perfectly liquid markets and it is evidently not viable in markets with imperfect liquidity (illiquid markets). It is well-known that markets with imperfect liquidity are more realistic. Thus, the presence of price impact while studying options is very important. This paper investigates a solution for the option pricing PDE in illiquid markets using the homotopy analysis method.

  5. Law of large numbers and central limit theorem for randomly forced PDE's

    CERN Document Server

    Shirikyan, A

    2004-01-01

    We consider a class of dissipative PDE's perturbed by an external random force. Under the condition that the distribution of perturbation is sufficiently non-degenerate, a strong law of large numbers (SLLN) and a central limit theorem (CLT) for solutions are established and the corresponding rates of convergence are estimated. It is also shown that the estimates obtained are close to being optimal. The proofs are based on the property of exponential mixing for the problem in question and some abstract SLLN and CLT for mixing-type Markov processes.

  6. Electromagnetic response in kinetic energy driven cuprate superconductors: Linear response approach

    International Nuclear Information System (INIS)

    Krzyzosiak, Mateusz; Huang, Zheyu; Feng, Shiping; Gonczarek, Ryszard

    2010-01-01

    Within the framework of the kinetic energy driven superconductivity, the electromagnetic response in cuprate superconductors is studied in the linear response approach. The kernel of the response function is evaluated and employed to calculate the local magnetic field profile, the magnetic field penetration depth, and the superfluid density, based on the specular reflection model for a purely transverse vector potential. It is shown that the low temperature magnetic field profile follows an exponential decay at the surface, while the magnetic field penetration depth depends linearly on temperature, except for the strong deviation from the linear characteristics at extremely low temperatures. The superfluid density is found to decrease linearly with decreasing doping concentration in the underdoped regime. The problem of gauge invariance is addressed and an approximation for the dressed current vertex, which does not violate local charge conservation is proposed and discussed.

  7. Partial differential equation-based approach for empirical mode decomposition: application on image analysis.

    Science.gov (United States)

    Niang, Oumar; Thioune, Abdoulaye; El Gueirea, Mouhamed Cheikh; Deléchelle, Eric; Lemoine, Jacques

    2012-09-01

    The major problem with the empirical mode decomposition (EMD) algorithm is its lack of a theoretical framework. So, it is difficult to characterize and evaluate this approach. In this paper, we propose, in the 2-D case, the use of an alternative implementation to the algorithmic definition of the so-called "sifting process" used in the original Huang's EMD method. This approach, especially based on partial differential equations (PDEs), was presented by Niang in previous works, in 2005 and 2007, and relies on a nonlinear diffusion-based filtering process to solve the mean envelope estimation problem. In the 1-D case, the efficiency of the PDE-based method, compared to the original EMD algorithmic version, was also illustrated in a recent paper. Recently, several 2-D extensions of the EMD method have been proposed. Despite some effort, 2-D versions for EMD appear poorly performing and are very time consuming. So in this paper, an extension to the 2-D space of the PDE-based approach is extensively described. This approach has been applied in cases of both signal and image decomposition. The obtained results confirm the usefulness of the new PDE-based sifting process for the decomposition of various kinds of data. Some results have been provided in the case of image decomposition. The effectiveness of the approach encourages its use in a number of signal and image applications such as denoising, detrending, or texture analysis.

  8. Kinetic approach to plasma end loss from linear devices

    International Nuclear Information System (INIS)

    Dreicer, H.

    1976-01-01

    A first step in the direction of a kinetic approach to end loss has been presented. This approach brings to light some fundamental processes not uncovered by the magnetohydrodynamic or guiding center approach. Attention was focused on the basically transient phenomenon in a way that describes the quite different behavior of collision dominated and collisionless ions, but ignores the magnetic nozzle effects near the ends of the system. The treatment illuminates some of the roles played by the parameter l/sub ii//L, and suggests the direction for more detailed investigations. End loss from linear systems is a very many faceted problem. Kinetic effects, magnetic effects, heat flow, etc. are all intermixed, and it will require a strong long term experimental and theoretical program to unravel all of its mysteries

  9. A kinetic approach to some quasi-linear laws of macroeconomics

    Science.gov (United States)

    Gligor, M.; Ignat, M.

    2002-11-01

    Some previous works have presented the data on wealth and income distributions in developed countries and have found that the great majority of population is described by an exponential distribution, which results in idea that the kinetic approach could be adequate to describe this empirical evidence. The aim of our paper is to extend this framework by developing a systematic kinetic approach of the socio-economic systems and to explain how linear laws, modelling correlations between macroeconomic variables, may arise in this context. Firstly we construct the Boltzmann kinetic equation for an idealised system composed by many individuals (workers, officers, business men, etc.), each of them getting a certain income and spending money for their needs. To each individual a certain time variable amount of money is associated this meaning him/her phase space coordinate. In this way the exponential distribution of money in a closed economy is explicitly found. The extension of this result, including states near the equilibrium, give us the possibility to take into account the regular increase of the total amount of money, according to the modern economic theories. The Kubo-Green-Onsager linear response theory leads us to a set of linear equations between some macroeconomic variables. Finally, the validity of such laws is discussed in relation with the time reversal symmetry and is tested empirically using some macroeconomic time series.

  10. Piecewise-linear and bilinear approaches to nonlinear differential equations approximation problem of computational structural mechanics

    OpenAIRE

    Leibov Roman

    2017-01-01

    This paper presents a bilinear approach to nonlinear differential equations system approximation problem. Sometimes the nonlinear differential equations right-hand sides linearization is extremely difficult or even impossible. Then piecewise-linear approximation of nonlinear differential equations can be used. The bilinear differential equations allow to improve piecewise-linear differential equations behavior and reduce errors on the border of different linear differential equations systems ...

  11. A linear programming approach for placement of applicants to academic programs

    OpenAIRE

    Kassa, Biniyam Asmare

    2013-01-01

    This paper reports a linear programming approach for placement of applicants to study programs developed and implemented at the college of Business & Economics, Bahir Dar University, Bahir Dar, Ethiopia. The approach is estimated to significantly streamline the placement decision process at the college by reducing required man hour as well as the time it takes to announce placement decisions. Compared to the previous manual system where only one or two placement criteria were considered, the ...

  12. Modified linear predictive coding approach for moving target tracking by Doppler radar

    Science.gov (United States)

    Ding, Yipeng; Lin, Xiaoyi; Sun, Ke-Hui; Xu, Xue-Mei; Liu, Xi-Yao

    2016-07-01

    Doppler radar is a cost-effective tool for moving target tracking, which can support a large range of civilian and military applications. A modified linear predictive coding (LPC) approach is proposed to increase the target localization accuracy of the Doppler radar. Based on the time-frequency analysis of the received echo, the proposed approach first real-time estimates the noise statistical parameters and constructs an adaptive filter to intelligently suppress the noise interference. Then, a linear predictive model is applied to extend the available data, which can help improve the resolution of the target localization result. Compared with the traditional LPC method, which empirically decides the extension data length, the proposed approach develops an error array to evaluate the prediction accuracy and thus, adjust the optimum extension data length intelligently. Finally, the prediction error array is superimposed with the predictor output to correct the prediction error. A series of experiments are conducted to illustrate the validity and performance of the proposed techniques.

  13. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    Science.gov (United States)

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Adaptive observer for the joint estimation of parameters and input for a coupled wave PDE and infinite dimensional ODE system

    KAUST Repository

    Belkhatir, Zehor; Mechhoud, Sarra; Laleg-Kirati, Taous-Meriem

    2016-01-01

    This paper deals with joint parameters and input estimation for coupled PDE-ODE system. The system consists of a damped wave equation and an infinite dimensional ODE. This model describes the spatiotemporal hemodynamic response in the brain

  15. Performance optimization of Sparse Matrix-Vector Multiplication for multi-component PDE-based applications using GPUs

    KAUST Repository

    Abdelfattah, Ahmad

    2016-05-23

    Simulations of many multi-component PDE-based applications, such as petroleum reservoirs or reacting flows, are dominated by the solution, on each time step and within each Newton step, of large sparse linear systems. The standard solver is a preconditioned Krylov method. Along with application of the preconditioner, memory-bound Sparse Matrix-Vector Multiplication (SpMV) is the most time-consuming operation in such solvers. Multi-species models produce Jacobians with a dense block structure, where the block size can be as large as a few dozen. Failing to exploit this dense block structure vastly underutilizes hardware capable of delivering high performance on dense BLAS operations. This paper presents a GPU-accelerated SpMV kernel for block-sparse matrices. Dense matrix-vector multiplications within the sparse-block structure leverage optimization techniques from the KBLAS library, a high performance library for dense BLAS kernels. The design ideas of KBLAS can be applied to block-sparse matrices. Furthermore, a technique is proposed to balance the workload among thread blocks when there are large variations in the lengths of nonzero rows. Multi-GPU performance is highlighted. The proposed SpMV kernel outperforms existing state-of-the-art implementations using matrices with real structures from different applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Performance optimization of Sparse Matrix-Vector Multiplication for multi-component PDE-based applications using GPUs

    KAUST Repository

    Abdelfattah, Ahmad; Ltaief, Hatem; Keyes, David E.; Dongarra, Jack

    2016-01-01

    Simulations of many multi-component PDE-based applications, such as petroleum reservoirs or reacting flows, are dominated by the solution, on each time step and within each Newton step, of large sparse linear systems. The standard solver is a preconditioned Krylov method. Along with application of the preconditioner, memory-bound Sparse Matrix-Vector Multiplication (SpMV) is the most time-consuming operation in such solvers. Multi-species models produce Jacobians with a dense block structure, where the block size can be as large as a few dozen. Failing to exploit this dense block structure vastly underutilizes hardware capable of delivering high performance on dense BLAS operations. This paper presents a GPU-accelerated SpMV kernel for block-sparse matrices. Dense matrix-vector multiplications within the sparse-block structure leverage optimization techniques from the KBLAS library, a high performance library for dense BLAS kernels. The design ideas of KBLAS can be applied to block-sparse matrices. Furthermore, a technique is proposed to balance the workload among thread blocks when there are large variations in the lengths of nonzero rows. Multi-GPU performance is highlighted. The proposed SpMV kernel outperforms existing state-of-the-art implementations using matrices with real structures from different applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Stability of Linear Equations--Algebraic Approach

    Science.gov (United States)

    Cherif, Chokri; Goldstein, Avraham; Prado, Lucio M. G.

    2012-01-01

    This article could be of interest to teachers of applied mathematics as well as to people who are interested in applications of linear algebra. We give a comprehensive study of linear systems from an application point of view. Specifically, we give an overview of linear systems and problems that can occur with the computed solution when the…

  18. A Generic High-performance GPU-based Library for PDE solvers

    DEFF Research Database (Denmark)

    Glimberg, Stefan Lemvig; Engsig-Karup, Allan Peter

    , the privilege of high-performance parallel computing is now in principle accessible for many scientific users, no matter their economic resources. Though being highly effective units, GPUs and parallel architectures in general, pose challenges for software developers to utilize their efficiency. Sequential...... legacy codes are not always easily parallelized and the time spent on conversion might not pay o in the end. We present a highly generic C++ library for fast assembling of partial differential equation (PDE) solvers, aiming at utilizing the computational resources of GPUs. The library requires a minimum...... of GPU computing knowledge, while still oering the possibility to customize user-specic solvers at kernel level if desired. Spatial dierential operators are based on matrix free exible order nite dierence approximations. These matrix free operators minimize both memory consumption and main memory access...

  19. The SR Approach: a new Estimation Method for Non-Linear and Non-Gaussian Dynamic Term Structure Models

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Christensen, Bent Jesper

    This paper suggests a new and easy approach to estimate linear and non-linear dynamic term structure models with latent factors. We impose no distributional assumptions on the factors and they may therefore be non-Gaussian. The novelty of our approach is to use many observables (yields or bonds p...

  20. A data fusion based approach for damage detection in linear systems

    Directory of Open Access Journals (Sweden)

    Ernesto Grande

    2014-07-01

    Full Text Available The aim of the present paper is to propose innovative approaches able to improve the capability of classical damage indicators in detecting the damage position in linear systems. In particular, starting from classical indicators based on the change of the flexibility matrix and on the change of the modal strain energy, the proposed approaches consider two data fusion procedures both based on the Dempster-Shafer theory. Numerical applications are reported in the paper in order to assess the reliability of the proposed approaches considering different damage scenarios, different sets of modes of vibration and the presence of errors affecting the accounted modes of vibrations.

  1. Groups, matrices, and vector spaces a group theoretic approach to linear algebra

    CERN Document Server

    Carrell, James B

    2017-01-01

    This unique text provides a geometric approach to group theory and linear algebra, bringing to light the interesting ways in which these subjects interact. Requiring few prerequisites beyond understanding the notion of a proof, the text aims to give students a strong foundation in both geometry and algebra. Starting with preliminaries (relations, elementary combinatorics, and induction), the book then proceeds to the core topics: the elements of the theory of groups and fields (Lagrange's Theorem, cosets, the complex numbers and the prime fields), matrix theory and matrix groups, determinants, vector spaces, linear mappings, eigentheory and diagonalization, Jordan decomposition and normal form, normal matrices, and quadratic forms. The final two chapters consist of a more intensive look at group theory, emphasizing orbit stabilizer methods, and an introduction to linear algebraic groups, which enriches the notion of a matrix group. Applications involving symm etry groups, determinants, linear coding theory ...

  2. An efficient linear approach in the reservoirs operation for electric power generation; Uma eficiente abordagem linear na operacao de reservatorios para geracao de energia eletrica

    Energy Technology Data Exchange (ETDEWEB)

    Zambon, Katia Livia

    1997-07-01

    A new approach for the Scheduling of Hydrothermal Systems, with a formulation that allows the solution of the problem through the linear programming techniques, otherwise the original form, which is complex and difficult is presented. The models were developed through a linear form for the generation function of hydroelectric plants, successive of the linearization of the cost function of the problem. The linear techniques used were the Simplex Method, with some modification that is is efficient, fast and simple. The important physical aspects of the system were preserved, like the individual representation of the hydroelectric plant, the features of cost function with the exponential increase and the head effect. Besides, this formulation can lead to stochastic approaches. All the optimization methods were implemented for the solution of the problem. The performance obtained were compared with each other and with that obtained through the non linear techniques. The algorithms showed to be efficient, with good results and very near to the optimal behavior of the reservoir operation planning obtained by traditional methods. (author)

  3. GREIT: a unified approach to 2D linear EIT reconstruction of lung images.

    Science.gov (United States)

    Adler, Andy; Arnold, John H; Bayford, Richard; Borsic, Andrea; Brown, Brian; Dixon, Paul; Faes, Theo J C; Frerichs, Inéz; Gagnon, Hervé; Gärber, Yvo; Grychtol, Bartłomiej; Hahn, Günter; Lionheart, William R B; Malik, Anjum; Patterson, Robert P; Stocks, Janet; Tizzard, Andrew; Weiler, Norbert; Wolf, Gerhard K

    2009-06-01

    Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use.

  4. GREIT: a unified approach to 2D linear EIT reconstruction of lung images

    International Nuclear Information System (INIS)

    Adler, Andy; Arnold, John H; Bayford, Richard; Tizzard, Andrew; Borsic, Andrea; Brown, Brian; Dixon, Paul; Faes, Theo J C; Frerichs, Inéz; Weiler, Norbert; Gagnon, Hervé; Gärber, Yvo; Grychtol, Bartłomiej; Hahn, Günter; Lionheart, William R B; Malik, Anjum; Patterson, Robert P; Stocks, Janet; Wolf, Gerhard K

    2009-01-01

    Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use

  5. Novel Approach to Linear Accelerator Superconducting Magnet System

    International Nuclear Information System (INIS)

    Kashikhin, Vladimir

    2011-01-01

    Superconducting Linear Accelerators include a superconducting magnet system for particle beam transportation that provides the beam focusing and steering. This system consists of a large number of quadrupole magnets and dipole correctors mounted inside or between cryomodules with SCRF cavities. Each magnet has current leads and powered from its own power supply. The paper proposes a novel approach to magnet powering based on using superconducting persistent current switches. A group of magnets is powered from the same power supply through the common, for the group of cryomodules, electrical bus and pair of current leads. Superconducting switches direct the current to the chosen magnet and close the circuit providing the magnet operation in a persistent current mode. Two persistent current switches were fabricated and tested. In the paper also presented the results of magnetic field simulations, decay time constants analysis, and a way of improving quadrupole magnetic center stability. Such approach substantially reduces the magnet system cost and increases the reliability.

  6. Practical application of equivalent linearization approaches to nonlinear piping systems

    International Nuclear Information System (INIS)

    Park, Y.J.; Hofmayer, C.H.

    1995-01-01

    The use of mechanical energy absorbers as an alternative to conventional hydraulic and mechanical snubbers for piping supports has attracted a wide interest among researchers and practitioners in the nuclear industry. The basic design concept of energy absorbers (EA) is to dissipate the vibration energy of piping systems through nonlinear hysteretic actions of EA exclamation point s under design seismic loads. Therefore, some type of nonlinear analysis needs to be performed in the seismic design of piping systems with EA supports. The equivalent linearization approach (ELA) can be a practical analysis tool for this purpose, particularly when the response approach (RSA) is also incorporated in the analysis formulations. In this paper, the following ELA/RSA methods are presented and compared to each other regarding their practice and numerical accuracy: Response approach using the square root of sum of squares (SRSS) approximation (denoted RS in this paper). Classical ELA based on modal combinations and linear random vibration theory (denoted CELA in this paper). Stochastic ELA based on direct solution of response covariance matrix (denoted SELA in this paper). New algorithms to convert response spectra to the equivalent power spectral density (PSD) functions are presented for both the above CELA and SELA methods. The numerical accuracy of the three EL are studied through a parametric error analysis. Finally, the practicality of the presented analysis is demonstrated in two application examples for piping systems with EA supports

  7. A feedback linearization approach to spacecraft control using momentum exchange devices. Ph.D. Thesis

    Science.gov (United States)

    Dzielski, John Edward

    1988-01-01

    Recent developments in the area of nonlinear control theory have shown how coordiante changes in the state and input spaces can be used with nonlinear feedback to transform certain nonlinear ordinary differential equations into equivalent linear equations. These feedback linearization techniques are applied to resolve two problems arising in the control of spacecraft equipped with control moment gyroscopes (CMGs). The first application involves the computation of rate commands for the gimbals that rotate the individual gyroscopes to produce commanded torques on the spacecraft. The second application is to the long-term management of stored momentum in the system of control moment gyroscopes using environmental torques acting on the vehicle. An approach to distributing control effort among a group of redundant actuators is described that uses feedback linearization techniques to parameterize sets of controls which influence a specified subsystem in a desired way. The approach is adapted for use in spacecraft control with double-gimballed gyroscopes to produce an algorithm that avoids problematic gimbal configurations by approximating sets of gimbal rates that drive CMG rotors into desirable configurations. The momentum management problem is stated as a trajectory optimization problem with a nonlinear dynamical constraint. Feedback linearization and collocation are used to transform this problem into an unconstrainted nonlinear program. The approach to trajectory optimization is fast and robust. A number of examples are presented showing applications to the proposed NASA space station.

  8. Closed-Form Formulas vs. PDE Based Numerical Solution for the FRAP Data Processing: Theoretical and Practical Comparison

    Czech Academy of Sciences Publication Activity Database

    Papáček, Š.; Macdonald, B.; Matonoha, Ctirad

    2017-01-01

    Roč. 73, č. 8 (2017), s. 1673-1683 ISSN 0898-1221 Grant - others:GA MŠk(CZ) ED2.1.00/01.0024; GA MŠk(CZ) LO1205 Institutional support: RVO:67985807 Keywords : fluorescence recovery after photobleaching (FRAP) * parameter estimation * sensitivity analysis * partial differential equation (PDE) Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 1.531, year: 2016

  9. Comparison of preconditioned Krylov subspace iteration methods for PDE-constrained optimization problems - Poisson and convection-diffusion control

    Czech Academy of Sciences Publication Activity Database

    Axelsson, Owe; Farouq, S.; Neytcheva, M.

    2016-01-01

    Roč. 73, č. 3 (2016), s. 631-633 ISSN 1017-1398 R&D Projects: GA MŠk ED1.1.00/02.0070 Institutional support: RVO:68145535 Keywords : PDE-constrained optimization problems * finite elements * iterative solution methods Subject RIV: BA - General Mathematics Impact factor: 1.241, year: 2016 http://link.springer.com/article/10.1007%2Fs11075-016-0111-1

  10. Electrostatic Discharge Current Linear Approach and Circuit Design Method

    Directory of Open Access Journals (Sweden)

    Pavlos K. Katsivelis

    2010-11-01

    Full Text Available The Electrostatic Discharge phenomenon is a great threat to all electronic devices and ICs. An electric charge passing rapidly from a charged body to another can seriously harm the last one. However, there is a lack in a linear mathematical approach which will make it possible to design a circuit capable of producing such a sophisticated current waveform. The commonly accepted Electrostatic Discharge current waveform is the one set by the IEC 61000-4-2. However, the over-simplified circuit included in the same standard is incapable of producing such a waveform. Treating the Electrostatic Discharge current waveform of the IEC 61000-4-2 as reference, an approximation method, based on Prony’s method, is developed and applied in order to obtain a linear system’s response. Considering a known input, a method to design a circuit, able to generate this ESD current waveform in presented. The circuit synthesis assumes ideal active elements. A simulation is carried out using the PSpice software.

  11. Solving large-scale PDE-constrained Bayesian inverse problems with Riemann manifold Hamiltonian Monte Carlo

    Science.gov (United States)

    Bui-Thanh, T.; Girolami, M.

    2014-11-01

    We consider the Riemann manifold Hamiltonian Monte Carlo (RMHMC) method for solving statistical inverse problems governed by partial differential equations (PDEs). The Bayesian framework is employed to cast the inverse problem into the task of statistical inference whose solution is the posterior distribution in infinite dimensional parameter space conditional upon observation data and Gaussian prior measure. We discretize both the likelihood and the prior using the H1-conforming finite element method together with a matrix transfer technique. The power of the RMHMC method is that it exploits the geometric structure induced by the PDE constraints of the underlying inverse problem. Consequently, each RMHMC posterior sample is almost uncorrelated/independent from the others providing statistically efficient Markov chain simulation. However this statistical efficiency comes at a computational cost. This motivates us to consider computationally more efficient strategies for RMHMC. At the heart of our construction is the fact that for Gaussian error structures the Fisher information matrix coincides with the Gauss-Newton Hessian. We exploit this fact in considering a computationally simplified RMHMC method combining state-of-the-art adjoint techniques and the superiority of the RMHMC method. Specifically, we first form the Gauss-Newton Hessian at the maximum a posteriori point and then use it as a fixed constant metric tensor throughout RMHMC simulation. This eliminates the need for the computationally costly differential geometric Christoffel symbols, which in turn greatly reduces computational effort at a corresponding loss of sampling efficiency. We further reduce the cost of forming the Fisher information matrix by using a low rank approximation via a randomized singular value decomposition technique. This is efficient since a small number of Hessian-vector products are required. The Hessian-vector product in turn requires only two extra PDE solves using the adjoint

  12. Angular spectrum approach for fast simulation of pulsed non-linear ultrasound fields

    DEFF Research Database (Denmark)

    Du, Yigang; Jensen, Henrik; Jensen, Jørgen Arendt

    2011-01-01

    The paper presents an Angular Spectrum Approach (ASA) for simulating pulsed non-linear ultrasound fields. The source of the ASA is generated by Field II, which can simulate array transducers of any arbitrary geometry and focusing. The non-linear ultrasound simulation program - Abersim, is used...... as the reference. A linear array transducer with 64 active elements is simulated by both Field II and Abersim. The excitation is a 2-cycle sine wave with a frequency of 5 MHz. The second harmonic field in the time domain is simulated using ASA. Pulse inversion is used in the Abersim simulation to remove...... the fundamental and keep the second harmonic field, since Abersim simulates non-linear fields with all harmonic components. ASA and Abersim are compared for the pulsed fundamental and second harmonic fields in the time domain at depths of 30 mm, 40 mm (focal depth) and 60 mm. Full widths at -6 dB (FWHM) are f0...

  13. The algebraic-hyperbolic approach to the linearized gravitational constraints on a Minkowski background

    International Nuclear Information System (INIS)

    Winicour, Jeffrey

    2017-01-01

    An algebraic-hyperbolic method for solving the Hamiltonian and momentum constraints has recently been shown to be well posed for general nonlinear perturbations of the initial data for a Schwarzschild black hole. This is a new approach to solving the constraints of Einstein’s equations which does not involve elliptic equations and has potential importance for the construction of binary black hole data. In order to shed light on the underpinnings of this approach, we consider its application to obtain solutions of the constraints for linearized perturbations of Minkowski space. In that case, we find the surprising result that there are no suitable Cauchy hypersurfaces in Minkowski space for which the linearized algebraic-hyperbolic constraint problem is well posed. (note)

  14. New approach to derive linear power/burnup history input for CANDU fuel codes

    International Nuclear Information System (INIS)

    Lac Tang, T.; Richards, M.; Parent, G.

    2003-01-01

    The fuel element linear power / burnup history is a required input for the ELESTRES code in order to simulate CANDU fuel behavior during normal operating conditions and also to provide input for the accident analysis codes ELOCA and SOURCE. The purpose of this paper is to present a new approach to derive 'true', or at least more realistic linear power / burnup histories. Such an approach can be used to recreate any typical bundle power history if only a single pair of instantaneous values of bundle power and burnup, together with the position in the channel, are known. The histories obtained could be useful to perform more realistic simulations for safety analyses for cases where the reference (overpower) history is not appropriate. (author)

  15. Status of the Monte Carlo library least-squares (MCLLS) approach for non-linear radiation analyzer problems

    Science.gov (United States)

    Gardner, Robin P.; Xu, Libai

    2009-10-01

    The Center for Engineering Applications of Radioisotopes (CEAR) has been working for over a decade on the Monte Carlo library least-squares (MCLLS) approach for treating non-linear radiation analyzer problems including: (1) prompt gamma-ray neutron activation analysis (PGNAA) for bulk analysis, (2) energy-dispersive X-ray fluorescence (EDXRF) analyzers, and (3) carbon/oxygen tool analysis in oil well logging. This approach essentially consists of using Monte Carlo simulation to generate the libraries of all the elements to be analyzed plus any other required background libraries. These libraries are then used in the linear library least-squares (LLS) approach with unknown sample spectra to analyze for all elements in the sample. Iterations of this are used until the LLS values agree with the composition used to generate the libraries. The current status of the methods (and topics) necessary to implement the MCLLS approach is reported. This includes: (1) the Monte Carlo codes such as CEARXRF, CEARCPG, and CEARCO for forward generation of the necessary elemental library spectra for the LLS calculation for X-ray fluorescence, neutron capture prompt gamma-ray analyzers, and carbon/oxygen tools; (2) the correction of spectral pulse pile-up (PPU) distortion by Monte Carlo simulation with the code CEARIPPU; (3) generation of detector response functions (DRF) for detectors with linear and non-linear responses for Monte Carlo simulation of pulse-height spectra; and (4) the use of the differential operator (DO) technique to make the necessary iterations for non-linear responses practical. In addition to commonly analyzed single spectra, coincidence spectra or even two-dimensional (2-D) coincidence spectra can also be used in the MCLLS approach and may provide more accurate results.

  16. Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.

    Science.gov (United States)

    Chino, Ayaka; Masuda, Naoyuki; Amano, Yasushi; Honbou, Kazuya; Mihara, Takuma; Yamazaki, Mayako; Tomishima, Masaki

    2014-07-01

    In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. Copyright © 2014. Published by Elsevier Ltd.

  17. FAST COMMUNICATION: A PDE Based Two Level Model of the Masking Property of the Human Ear

    OpenAIRE

    Xin, Jack; Qi, Yingyong

    2003-01-01

    Human ear has the masking property that certain audible sound becomes inaudible in the presence of another sound. Masking is quantified by the raised threshold from the absolute hearing threshold in quiet. It is of scientific and practical importance to compute masking thresholds. Empirical models on masking have applications in low bit rate digital music compression. A first principle based two level model is developed with partial differential equation (PDE) at the periphe...

  18. A novel linear programming approach to fluence map optimization for intensity modulated radiation therapy treatment planning

    International Nuclear Information System (INIS)

    Romeijn, H Edwin; Ahuja, Ravindra K; Dempsey, James F; Kumar, Arvind; Li, Jonathan G

    2003-01-01

    We present a novel linear programming (LP) based approach for efficiently solving the intensity modulated radiation therapy (IMRT) fluence-map optimization (FMO) problem to global optimality. Our model overcomes the apparent limitations of a linear-programming approach by approximating any convex objective function by a piecewise linear convex function. This approach allows us to retain the flexibility offered by general convex objective functions, while allowing us to formulate the FMO problem as a LP problem. In addition, a novel type of partial-volume constraint that bounds the tail averages of the differential dose-volume histograms of structures is imposed while retaining linearity as an alternative approach to improve dose homogeneity in the target volumes, and to attempt to spare as many critical structures as possible. The goal of this work is to develop a very rapid global optimization approach that finds high quality dose distributions. Implementation of this model has demonstrated excellent results. We found globally optimal solutions for eight 7-beam head-and-neck cases in less than 3 min of computational time on a single processor personal computer without the use of partial-volume constraints. Adding such constraints increased the running times by a factor of 2-3, but improved the sparing of critical structures. All cases demonstrated excellent target coverage (>95%), target homogeneity (<10% overdosing and <7% underdosing) and organ sparing using at least one of the two models

  19. Efficient optimization of electrostatic interactions between biomolecules.

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, J. P.; Altman, M. D.; White, J. K.; Tidor, B.; Mathematics and Computer Science; MIT

    2007-01-01

    We present a PDE-constrained approach to optimizing the electrostatic interactions between two biomolecules. These interactions play important roles in the determination of binding affinity and specificity, and are therefore of significant interest when designing a ligand molecule to bind tightly to a receptor. Using a popular continuum model and physically reasonable assumptions, the electrostatic component of the binding free energy is a convex, quadratic function of the ligand charge distribution. Traditional optimization methods require exhaustive pre-computation, and the expense has precluded a full exploration of the promise of electrostatic optimization in biomolecule analysis and design. In this paper we describe an approach in which the electrostatic simulations and optimization problem are solved simultaneously; unlike many PDE- constrained optimization frameworks, the proposed method does not incorporate the PDE as a set of equality constraints. This co-optimization approach can be used by itself to solve unconstrained problems or those with linear equality constraints, or in conjunction with primal-dual interior point methods to solve problems with inequality constraints. Model problems demonstrate that the co-optimization method is computationally efficient and can be used to solve realistic problems.

  20. Economic planning for electric energy systems: a multi objective linearized approach for solution

    International Nuclear Information System (INIS)

    Mata Medeiros Branco, T. da.

    1986-01-01

    The economic planning problem associated to the expansion and operation of electrical power systems is considered in this study, represented for a vectorial objective function in which the minimization of resources involved and maximization of attended demand constitute goals to be satisfied. Supposing all the variables involved with linear characteristic and considering the conflict existing among the objectives to be achieved, in order to find a solution, a multi objective linearized approach is proposed. This approximation utilizes the compromise programming technique and linear programming methods. Generation and transmission are simultaneously considered into the optimization process in which associated losses and the capacity of each line are included. Illustrated examples are also presented with results discussed. (author)

  1. A PDE-constrained SQP algorithm for optical tomography based on the frequency-domain equation of radiative transfer

    International Nuclear Information System (INIS)

    Kim, Hyun Keol; Hielscher, Andreas H

    2009-01-01

    It is well acknowledged that transport-theory-based reconstruction algorithm can provide the most accurate reconstruction results especially when small tissue volumes or high absorbing media are considered. However, these codes have a high computational burden and are often only slowly converging. Therefore, methods that accelerate the computation are highly desirable. To this end, we introduce in this work a partial-differential-equation (PDE) constrained approach to optical tomography that makes use of an all-at-once reduced Hessian sequential quadratic programming (rSQP) scheme. The proposed scheme treats the forward and inverse variables independently, which makes it possible to update the radiation intensities and the optical coefficients simultaneously by solving the forward and inverse problems, all at once. We evaluate the performance of the proposed scheme with numerical and experimental data, and find that the rSQP scheme can reduce the computation time by a factor of 10–25, as compared to the commonly employed limited memory BFGS method. At the same time accuracy and robustness even in the presence of noise are not compromised

  2. Dynamics and control of quadcopter using linear model predictive control approach

    Science.gov (United States)

    Islam, M.; Okasha, M.; Idres, M. M.

    2017-12-01

    This paper investigates the dynamics and control of a quadcopter using the Model Predictive Control (MPC) approach. The dynamic model is of high fidelity and nonlinear, with six degrees of freedom that include disturbances and model uncertainties. The control approach is developed based on MPC to track different reference trajectories ranging from simple ones such as circular to complex helical trajectories. In this control technique, a linearized model is derived and the receding horizon method is applied to generate the optimal control sequence. Although MPC is computer expensive, it is highly effective to deal with the different types of nonlinearities and constraints such as actuators’ saturation and model uncertainties. The MPC parameters (control and prediction horizons) are selected by trial-and-error approach. Several simulation scenarios are performed to examine and evaluate the performance of the proposed control approach using MATLAB and Simulink environment. Simulation results show that this control approach is highly effective to track a given reference trajectory.

  3. Complexity analysis of accelerated MCMC methods for Bayesian inversion

    International Nuclear Information System (INIS)

    Hoang, Viet Ha; Schwab, Christoph; Stuart, Andrew M

    2013-01-01

    The Bayesian approach to inverse problems, in which the posterior probability distribution on an unknown field is sampled for the purposes of computing posterior expectations of quantities of interest, is starting to become computationally feasible for partial differential equation (PDE) inverse problems. Balancing the sources of error arising from finite-dimensional approximation of the unknown field, the PDE forward solution map and the sampling of the probability space under the posterior distribution are essential for the design of efficient computational Bayesian methods for PDE inverse problems. We study Bayesian inversion for a model elliptic PDE with an unknown diffusion coefficient. We provide complexity analyses of several Markov chain Monte Carlo (MCMC) methods for the efficient numerical evaluation of expectations under the Bayesian posterior distribution, given data δ. Particular attention is given to bounds on the overall work required to achieve a prescribed error level ε. Specifically, we first bound the computational complexity of ‘plain’ MCMC, based on combining MCMC sampling with linear complexity multi-level solvers for elliptic PDE. Our (new) work versus accuracy bounds show that the complexity of this approach can be quite prohibitive. Two strategies for reducing the computational complexity are then proposed and analyzed: first, a sparse, parametric and deterministic generalized polynomial chaos (gpc) ‘surrogate’ representation of the forward response map of the PDE over the entire parameter space, and, second, a novel multi-level Markov chain Monte Carlo strategy which utilizes sampling from a multi-level discretization of the posterior and the forward PDE. For both of these strategies, we derive asymptotic bounds on work versus accuracy, and hence asymptotic bounds on the computational complexity of the algorithms. In particular, we provide sufficient conditions on the regularity of the unknown coefficients of the PDE and on the

  4. Introducing Linear Functions: An Alternative Statistical Approach

    Science.gov (United States)

    Nolan, Caroline; Herbert, Sandra

    2015-01-01

    The introduction of linear functions is the turning point where many students decide if mathematics is useful or not. This means the role of parameters and variables in linear functions could be considered to be "threshold concepts". There is recognition that linear functions can be taught in context through the exploration of linear…

  5. Tissue characterization using electrical impedance spectroscopy data: a linear algebra approach.

    Science.gov (United States)

    Laufer, Shlomi; Solomon, Stephen B; Rubinsky, Boris

    2012-06-01

    In this study, we use a new linear algebra manipulation on electrical impedance spectroscopy measurements to provide real-time information regarding the nature of the tissue surrounding the needle in minimal invasive procedures. Using a Comsol Multiphysics three-dimensional model, a phantom based on ex vivo animal tissue and in vivo animal data, we demonstrate how tissue inhomogeneity can be characterized without any previous knowledge of the electrical properties of the different tissues, except that they should not be linearly dependent on a certain frequency range. This method may have applications in needle biopsies, radiation seeds, or minimally invasive surgery and can reduce the number of computer tomography or magnetic resonance imaging images. We conclude by demonstrating how this mathematical approach can be useful in other applications.

  6. Transition to Coherence in Populations of Coupled Chaotic Oscillators: A Linear Response Approach

    International Nuclear Information System (INIS)

    Topaj, Dmitri; Kye, Won-Ho; Pikovsky, Arkady

    2001-01-01

    We consider the collective dynamics in an ensemble of globally coupled chaotic maps. The transition to the coherent state with a macroscopic mean field is analyzed in the framework of the linear response theory. The linear response function for the chaotic system is obtained using the perturbation approach to the Frobenius-Perron operator. The transition point is defined from this function by virtue of the self-excitation condition for the feedback loop. Analytical results for the coupled Bernoulli maps are confirmed by the numerics

  7. Assessment of sperm quality, oxidative stress injury as well as ACP, AC and PDE expression in patients with oligoasthenozoospermia before and after qilin pill treatment

    Directory of Open Access Journals (Sweden)

    Shi-Jun Zhang

    2016-09-01

    Full Text Available Objective: To analyze the sperm quality, oxidative stress injury as well as ACP, AC and PDE expression in patients with oligoasthenozoospermia before and after qilin pill treatment. Methods: A total of 60 patients with oligoasthenozoospermia were randomly divided into observation group and control group, control group received routine western medicine treatment, observation group received qilin pill + conventional western medicine treatment, and then differences in sperm quality, oxidative stress injury, ACP, AC and PDE expression, etc. were compared between two groups after treatment. Results: Semen volume and sperm density in semen samples of observation group after qilin pill treatment were higher than those of control group; serum FSH and LH levels were lower than those of control group, and the T level was higher than that of control group; ROS and MDA levels in seminal plasma were lower than those of control group, and SOD level was higher than that of control group; ACP, AC, α-Glu and Fru levels in seminal plasma were higher than those of control group, and PDE level was lower than that of control group. Conclusion: Qilin pill can improve sperm quality and optimize testicular internal environment in patients with oligoasthenozoospermia, and it has positive clinical significance.

  8. An equivalent frequency approach for determining non-linear effects on pre-tensioned-cable cross-braced structures

    Science.gov (United States)

    Giaccu, Gian Felice

    2018-05-01

    Pre-tensioned cable braces are widely used as bracing systems in various structural typologies. This technology is fundamentally utilized for stiffening purposes in the case of steel and timber structures. The pre-stressing force imparted to the braces provides to the system a remarkable increment of stiffness. On the other hand, the pre-tensioning force in the braces must be properly calibrated in order to satisfactorily meet both serviceability and ultimate limit states. Dynamic properties of these systems are however affected by non-linear behavior due to potential slackening of the pre-tensioned brace. In the recent years the author has been working on a similar problem regarding the non-linear response of cables in cable-stayed bridges and braced structures. In the present paper a displacement-based approach is used to examine the non-linear behavior of a building system. The methodology operates through linearization and allows obtaining an equivalent linearized frequency to approximately characterize, mode by mode, the dynamic behavior of the system. The equivalent frequency depends on both the mechanical characteristics of the system, the pre-tensioning level assigned to the braces and a characteristic vibration amplitude. The proposed approach can be used as a simplified technique, capable of linearizing the response of structural systems, characterized by non-linearity induced by the slackening of pre-tensioned braces.

  9. Linear mixed-effects modeling approach to FMRI group analysis.

    Science.gov (United States)

    Chen, Gang; Saad, Ziad S; Britton, Jennifer C; Pine, Daniel S; Cox, Robert W

    2013-06-01

    Conventional group analysis is usually performed with Student-type t-test, regression, or standard AN(C)OVA in which the variance-covariance matrix is presumed to have a simple structure. Some correction approaches are adopted when assumptions about the covariance structure is violated. However, as experiments are designed with different degrees of sophistication, these traditional methods can become cumbersome, or even be unable to handle the situation at hand. For example, most current FMRI software packages have difficulty analyzing the following scenarios at group level: (1) taking within-subject variability into account when there are effect estimates from multiple runs or sessions; (2) continuous explanatory variables (covariates) modeling in the presence of a within-subject (repeated measures) factor, multiple subject-grouping (between-subjects) factors, or the mixture of both; (3) subject-specific adjustments in covariate modeling; (4) group analysis with estimation of hemodynamic response (HDR) function by multiple basis functions; (5) various cases of missing data in longitudinal studies; and (6) group studies involving family members or twins. Here we present a linear mixed-effects modeling (LME) methodology that extends the conventional group analysis approach to analyze many complicated cases, including the six prototypes delineated above, whose analyses would be otherwise either difficult or unfeasible under traditional frameworks such as AN(C)OVA and general linear model (GLM). In addition, the strength of the LME framework lies in its flexibility to model and estimate the variance-covariance structures for both random effects and residuals. The intraclass correlation (ICC) values can be easily obtained with an LME model with crossed random effects, even at the presence of confounding fixed effects. The simulations of one prototypical scenario indicate that the LME modeling keeps a balance between the control for false positives and the sensitivity

  10. The pricing of firm bonds with extendable maturity by the reduced form approach

    Directory of Open Access Journals (Sweden)

    REN Xuemin

    2012-10-01

    Full Text Available We associate credit events with market rates to price firm bonds with extendable maturity.We deal with the credit risk by the reduced form approach and obtain the pricing formula for firm bonds with extendable maturity by the PDE approach under the assumption of stochastic interest rate and compare its return rate with that of ordinary firm bonds.

  11. Implementing nonprojective measurements via linear optics: An approach based on optimal quantum-state discrimination

    International Nuclear Information System (INIS)

    Loock, Peter van; Nemoto, Kae; Munro, William J.; Raynal, Philippe; Luetkenhaus, Norbert

    2006-01-01

    We discuss the problem of implementing generalized measurements [positive operator-valued measures (POVMs)] with linear optics, either based upon a static linear array or including conditional dynamics. In our approach, a given POVM shall be identified as a solution to an optimization problem for a chosen cost function. We formulate a general principle: the implementation is only possible if a linear-optics circuit exists for which the quantum mechanical optimum (minimum) is still attainable after dephasing the corresponding quantum states. The general principle enables us, for instance, to derive a set of necessary conditions for the linear-optics implementation of the POVM that realizes the quantum mechanically optimal unambiguous discrimination of two pure nonorthogonal states. This extends our previous results on projection measurements and the exact discrimination of orthogonal states

  12. Tissue characterization using electrical impedance spectroscopy data: a linear algebra approach

    International Nuclear Information System (INIS)

    Laufer, Shlomi; Solomon, Stephen B; Rubinsky, Boris

    2012-01-01

    In this study, we use a new linear algebra manipulation on electrical impedance spectroscopy measurements to provide real-time information regarding the nature of the tissue surrounding the needle in minimal invasive procedures. Using a Comsol Multiphysics three-dimensional model, a phantom based on ex vivo animal tissue and in vivo animal data, we demonstrate how tissue inhomogeneity can be characterized without any previous knowledge of the electrical properties of the different tissues, except that they should not be linearly dependent on a certain frequency range. This method may have applications in needle biopsies, radiation seeds, or minimally invasive surgery and can reduce the number of computer tomography or magnetic resonance imaging images. We conclude by demonstrating how this mathematical approach can be useful in other applications. (paper)

  13. Continuous dynamic assimilation of the inner region data in hydrodynamics modelling: optimization approach

    Directory of Open Access Journals (Sweden)

    F. I. Pisnitchenko

    2008-11-01

    Full Text Available In meteorological and oceanological studies the classical approach for finding the numerical solution of the regional model consists in formulating and solving a Cauchy-Dirichlet problem. The boundary conditions are obtained by linear interpolation of coarse-grid data provided by a global model. Errors in boundary conditions due to interpolation may cause large deviations from the correct regional solution. The methods developed to reduce these errors deal with continuous dynamic assimilation of known global data available inside the regional domain. One of the approaches of this assimilation procedure performs a nudging of large-scale components of regional model solution to large-scale global data components by introducing relaxation forcing terms into the regional model equations. As a result, the obtained solution is not a valid numerical solution to the original regional model. Another approach is the use a four-dimensional variational data assimilation procedure which is free from the above-mentioned shortcoming. In this work we formulate the joint problem of finding the regional model solution and data assimilation as a PDE-constrained optimization problem. Three simple model examples (ODE Burgers equation, Rossby-Oboukhov equation, Korteweg-de Vries equation are considered in this paper. Numerical experiments indicate that the optimization approach can significantly improve the precision of the regional solution.

  14. Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family.

    Science.gov (United States)

    Hmani-Aifa, Mounira; Benzina, Zeineb; Zulfiqar, Fareeha; Dhouib, Houria; Shahzadi, Amber; Ghorbel, Abdelmonem; Rebaï, Ahmed; Söderkvist, Peter; Riazuddin, Sheikh; Kimberling, William J; Ayadi, Hammadi

    2009-04-01

    Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disorder. ARRP could be associated with extraocular manifestations that define specific syndromes such as Usher syndrome (USH) characterized by retinal degeneration and congenital hearing loss (HL). The USH type II (USH2) associates RP and mild-to-moderate HL with preserved vestibular function. At least three genes USH2A, the very large G-protein-coupled receptor, GPR98, and DFNB31 are responsible for USH2 syndrome. Here, we report on the segregation of non-syndromic ARRP and USH2 syndrome in a consanguineous Tunisian family, which was previously used to define USH2B locus. With regard to the co-occurrence of these two different pathologies, clinical and genetic reanalysis of the extended family showed (i) phenotypic heterogeneity within USH2 patients and (ii) excluded linkage to USH2B locus. Indeed, linkage analysis disclosed the cosegregation of the USH2 phenotype with the USH2C locus markers, D5S428 and D5S618, whereas the ARRP perfectly segregates with PDE6B flanking markers D4S3360 and D4S2930. Molecular analysis revealed two new missense mutations, p.Y6044C and p.W807R, occurring in GPR98 and PDE6B genes, respectively. In conclusion, our results show that the USH2B locus at chromosome 3p23-24.2 does not exist, and we therefore withdraw this locus designation. The combination of molecular findings for GPR98 and PDE6B genes enable us to explain the phenotypic heterogeneity and particularly the severe ocular affection first observed in one USH2 patient. This report presents an illustration of how consanguinity could increase familial clustering of multiple hereditary diseases within the same family.

  15. Approach to assurance of reliability of linear accelerator operation observations

    International Nuclear Information System (INIS)

    Bakov, S.M.; Borovikov, A.A.; Kavkun, S.L.

    1994-01-01

    The system approach to solving the task of assuring reliability of observations over the linear accelerator operation is proposed. The basic principles of this method consist in application of dependences between the facility parameters, decrease in the number of the system apparatus channels for data acquisition without replacement of failed channel by reserve one. The signal commutation unit, the introduction whereof into the data acquisition system essentially increases the reliability of the measurement system on the account of active reserve, is considered detail. 8 refs. 6 figs

  16. Quantitative Assessment of Arrhythmia Using Non-linear Approach: A Non-invasive Prognostic Tool

    Science.gov (United States)

    Chakraborty, Monisha; Ghosh, Dipak

    2018-04-01

    Accurate prognostic tool to identify severity of Arrhythmia is yet to be investigated, owing to the complexity of the ECG signal. In this paper, we have shown that quantitative assessment of Arrhythmia is possible using non-linear technique based on "Hurst Rescaled Range Analysis". Although the concept of applying "non-linearity" for studying various cardiac dysfunctions is not entirely new, the novel objective of this paper is to identify the severity of the disease, monitoring of different medicine and their dose, and also to assess the efficiency of different medicine. The approach presented in this work is simple which in turn will help doctors in efficient disease management. In this work, Arrhythmia ECG time series are collected from MIT-BIH database. Normal ECG time series are acquired using POLYPARA system. Both time series are analyzed in thelight of non-linear approach following the method "Rescaled Range Analysis". The quantitative parameter, "Fractal Dimension" (D) is obtained from both types of time series. The major finding is that Arrhythmia ECG poses lower values of D as compared to normal. Further, this information can be used to access the severity of Arrhythmia quantitatively, which is a new direction of prognosis as well as adequate software may be developed for the use of medical practice.

  17. Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk

    Science.gov (United States)

    2008-04-01

    arrays. Methods Mol Biol 2002;200:87–100. [78] Craig JM, Kraus J, Cremer T. Removal of repetitive sequences from FISH probes using PCR-assisted affinity...Worcester, MA), David Hepps, MD, and Lynn Birch for technical contributions. Figure 5. Alterations in PDE4D4 CpG methylation and gene expression in NbE-1

  18. Wireless Positioning Based on a Segment-Wise Linear Approach for Modeling the Target Trajectory

    DEFF Research Database (Denmark)

    Figueiras, Joao; Pedersen, Troels; Schwefel, Hans-Peter

    2008-01-01

    Positioning solutions in infrastructure-based wireless networks generally operate by exploiting the channel information of the links between the Wireless Devices and fixed networking Access Points. The major challenge of such solutions is the modeling of both the noise properties of the channel...... measurements and the user mobility patterns. One class of typical human being movement patterns is the segment-wise linear approach, which is studied in this paper. Current tracking solutions, such as the Constant Velocity model, hardly handle such segment-wise linear patterns. In this paper we propose...... a segment-wise linear model, called the Drifting Points model. The model results in an increased performance when compared with traditional solutions....

  19. A novel approach to linearization of the electromagnetic parameters of tokamaks with an iron core

    Energy Technology Data Exchange (ETDEWEB)

    Fu, P. E-mail: fupeng@mail.ipp.ac.cn; Liu, Z.Z.; Zou, J.H

    2002-05-01

    The equivalent model of an iron core tokamak is developed, in which the electromagnetic parameters of several pairs of coils in opposite series (PCOS) are not dependent on the saturation of the iron core during tokamak operation. With this the electromagnetic parameters of all the coils in an iron core tokamak can be linearized, As an example, the electromagnetic parameters of Hefei Super-conductive Tokamak with iron core (HT-7) are linearized, and it is in good agreement with the experimental results. The linearization approach can be applied in real time plasma control and electromagnetic analysis.

  20. Linear algebra

    CERN Document Server

    Edwards, Harold M

    1995-01-01

    In his new undergraduate textbook, Harold M Edwards proposes a radically new and thoroughly algorithmic approach to linear algebra Originally inspired by the constructive philosophy of mathematics championed in the 19th century by Leopold Kronecker, the approach is well suited to students in the computer-dominated late 20th century Each proof is an algorithm described in English that can be translated into the computer language the class is using and put to work solving problems and generating new examples, making the study of linear algebra a truly interactive experience Designed for a one-semester course, this text adopts an algorithmic approach to linear algebra giving the student many examples to work through and copious exercises to test their skills and extend their knowledge of the subject Students at all levels will find much interactive instruction in this text while teachers will find stimulating examples and methods of approach to the subject

  1. EVA – a non-linear Eulerian approach for assessment of health-cost externalities of air pollution

    DEFF Research Database (Denmark)

    Andersen, Mikael Skou; Frohn, Lise Marie; Nielsen, Jytte Seested

    2006-01-01

    of the emissions. External cost estimates based on the Eulerian approach, on the other hand, are in mutual conformity. The existence of non-linear dynamics and possible thresholds, both in the atmospheric modelling and in the dose-response functions for health effects, need further attention and should......Integrated models which are used to account for the external costs of air pollution have to a considerable extent ignored the non-linear dynamics of atmospheric science. In order to bridge the gap between economic analysis and environmental modelling an integrated model EVA, based on a Eulerian...... for the final external cost estimates of the Eulerian approach is explored. Uncertainties in the health costs estimates are endemic in particular for mortality, but in order to achieve a common baseline the approach recommended by the OECD has been employed for the valuation part. This approach implies the use...

  2. A penalization approach to linear programming duality with application to capacity constrained transport

    OpenAIRE

    Korman, Jonathan; McCann, Robert J.; Seis, Christian

    2013-01-01

    A new approach to linear programming duality is proposed which relies on quadratic penalization, so that the relation between solutions to the penalized primal and dual problems becomes affine. This yields a new proof of Levin's duality theorem for capacity-constrained optimal transport as an infinite-dimensional application.

  3. A linear programming approach for placement of applicants to academic programs.

    Science.gov (United States)

    Kassa, Biniyam Asmare

    2013-01-01

    This paper reports a linear programming approach for placement of applicants to study programs developed and implemented at the college of Business & Economics, Bahir Dar University, Bahir Dar, Ethiopia. The approach is estimated to significantly streamline the placement decision process at the college by reducing required man hour as well as the time it takes to announce placement decisions. Compared to the previous manual system where only one or two placement criteria were considered, the new approach allows the college's management to easily incorporate additional placement criteria, if needed. Comparison of our approach against manually constructed placement decisions based on actual data for the 2012/13 academic year suggested that about 93 percent of the placements from our model concur with the actual placement decisions. For the remaining 7 percent of placements, however, the actual placements made by the manual system display inconsistencies of decisions judged against the very criteria intended to guide placement decisions by the college's program management office. Overall, the new approach proves to be a significant improvement over the manual system in terms of efficiency of the placement process and the quality of placement decisions.

  4. SLFP: a stochastic linear fractional programming approach for sustainable waste management.

    Science.gov (United States)

    Zhu, H; Huang, G H

    2011-12-01

    A stochastic linear fractional programming (SLFP) approach is developed for supporting sustainable municipal solid waste management under uncertainty. The SLFP method can solve ratio optimization problems associated with random information, where chance-constrained programming is integrated into a linear fractional programming framework. It has advantages in: (1) comparing objectives of two aspects, (2) reflecting system efficiency, (3) dealing with uncertainty expressed as probability distributions, and (4) providing optimal-ratio solutions under different system-reliability conditions. The method is applied to a case study of waste flow allocation within a municipal solid waste (MSW) management system. The obtained solutions are useful for identifying sustainable MSW management schemes with maximized system efficiency under various constraint-violation risks. The results indicate that SLFP can support in-depth analysis of the interrelationships among system efficiency, system cost and system-failure risk. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Linear response theory an analytic-algebraic approach

    CERN Document Server

    De Nittis, Giuseppe

    2017-01-01

    This book presents a modern and systematic approach to Linear Response Theory (LRT) by combining analytic and algebraic ideas. LRT is a tool to study systems that are driven out of equilibrium by external perturbations. In particular the reader is provided with a new and robust tool to implement LRT for a wide array of systems. The proposed formalism in fact applies to periodic and random systems in the discrete and the continuum. After a short introduction describing the structure of the book, its aim and motivation, the basic elements of the theory are presented in chapter 2. The mathematical framework of the theory is outlined in chapters 3–5: the relevant von Neumann algebras, noncommutative $L^p$- and Sobolev spaces are introduced; their construction is then made explicit for common physical systems; the notion of isopectral perturbations and the associated dynamics are studied. Chapter 6 is dedicated to the main results, proofs of the Kubo and Kubo-Streda formulas. The book closes with a chapter about...

  6. Fast simulation of non-linear pulsed ultrasound fields using an angular spectrum approach

    DEFF Research Database (Denmark)

    Du, Yigang; Jensen, Jørgen Arendt

    2013-01-01

    A fast non-linear pulsed ultrasound field simulation is presented. It is implemented based on an angular spectrum approach (ASA), which analytically solves the non-linear wave equation. The ASA solution to the Westervelt equation is derived in detail. The calculation speed is significantly...... increased compared to a numerical solution using an operator splitting method (OSM). The ASA has been modified and extended to pulsed non-linear ultrasound fields in combination with Field II, where any array transducer with arbitrary geometry, excitation, focusing and apodization can be simulated...... with a center frequency of 5 MHz. The speed is increased approximately by a factor of 140 and the calculation time is 12 min with a standard PC, when simulating the second harmonic pulse at the focal point. For the second harmonic point spread function the full width error is 1.5% at 6 dB and 6.4% at 12 d...

  7. Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation

    Science.gov (United States)

    Hoppmann, Julia; Gesing, Julia; Silve, Caroline; Leroy, Chrystel; Bertsche, Astrid; Hirsch, Franz Wolfgang; Kiess, Wieland; Pfäffle, Roland; Schuster, Volker

    2017-01-01

    Acrodysostosis is a very rare congenital multisystem condition characterized by skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short stature, varying degrees of intellectual disability, and possible resistance to multiple G protein-coupled receptor signalling hormones. Two distinct subtypes are differentiated: acrodysostosis type 1 resulting from defects in protein kinase type 1-α regulatory subunit and acrodysostosis type 2 caused by mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on a rare multigenerational familial case of acrodysostosis type 2 due to a novel autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with short stature, midfacial hypoplasia, severe brachydactyly, developmental delay, and behavioural problems. Laboratory investigations revealed mild thyrotropin resistance. His mother shared some characteristic features, such as midfacial hypoplasia and severe brachydactyly, but did not show short stature, intellectual disability or hormonal resistance. Genetic analysis identified the identical, novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in both patients. This case illustrates the significant phenotypic variability of acrodysostosis even within one family with identical mutations. Hence, a specific clinical diagnosis of acrodysostosis remains challenging because of great interindividual variability and a substantial overlap of the two subtypes as well as with other related Gsα-cAMP-signalling-linked disorders. PMID:28515031

  8. Dynamics with Matrices Possessing Kronecker Product Structure

    KAUST Repository

    Łoś, M.

    2015-06-01

    In this paper we present an application of Alternating Direction Implicit (ADI) algorithm for solution of non-stationary PDE-s using isogeometric finite element method. We show that ADI algorithm has a linear computational cost at every time step. We illustrate this approach by solving two example non-stationary three-dimensional problems using explicit Euler and Newmark time-stepping scheme: heat equation and linear elasticity equations for a cube. The stability of the simulation is controlled by monitoring the energy of the solution.

  9. Dynamics with Matrices Possessing Kronecker Product Structure

    KAUST Repository

    Łoś, M.; Wó zniak, M.; Paszynśki, M.; Dalcin, L.; Calo, Victor M.

    2015-01-01

    In this paper we present an application of Alternating Direction Implicit (ADI) algorithm for solution of non-stationary PDE-s using isogeometric finite element method. We show that ADI algorithm has a linear computational cost at every time step. We illustrate this approach by solving two example non-stationary three-dimensional problems using explicit Euler and Newmark time-stepping scheme: heat equation and linear elasticity equations for a cube. The stability of the simulation is controlled by monitoring the energy of the solution.

  10. Study on infrared multiphoton excitation of the linear triatomic molecule by the Lie-algebra approach

    International Nuclear Information System (INIS)

    Feng, H.; Zheng, Y.; Ding, S.

    2007-01-01

    Infrared multiphoton vibrational excitation of the linear triatomic molecule has been studied using the quadratic anharmonic Lie-algebra model, unitary transformations, and Magnus approximation. An explicit Lie-algebra expression for the vibrational transition probability is obtained by using a Lie-algebra approach. This explicit Lie-algebra expressions for time-evolution operator and vibrational transition probabilities make the computation clearer and easier. The infrared multiphoton vibrational excitation of the DCN linear tri-atomic molecule is discussed as an example

  11. Penalized linear regression for discrete ill-posed problems: A hybrid least-squares and mean-squared error approach

    KAUST Repository

    Suliman, Mohamed Abdalla Elhag; Ballal, Tarig; Kammoun, Abla; Al-Naffouri, Tareq Y.

    2016-01-01

    This paper proposes a new approach to find the regularization parameter for linear least-squares discrete ill-posed problems. In the proposed approach, an artificial perturbation matrix with a bounded norm is forced into the discrete ill-posed model

  12. Muscle MRS detects elevated PDE/ATP ratios prior to fatty infiltration in Becker muscular dystrophy.

    Science.gov (United States)

    Wokke, B H; Hooijmans, M T; van den Bergen, J C; Webb, A G; Verschuuren, J J; Kan, H E

    2014-11-01

    Becker muscular dystrophy (BMD) is characterized by progressive muscle weakness. Muscles show structural changes (fatty infiltration, fibrosis) and metabolic changes, both of which can be assessed using MRI and MRS. It is unknown at what stage of the disease process metabolic changes arise and how this might vary for different metabolites. In this study we assessed metabolic changes in skeletal muscles of Becker patients, both with and without fatty infiltration, quantified via Dixon MRI and (31) P MRS. MRI and (31) P MRS scans were obtained from 25 Becker patients and 14 healthy controls using a 7 T MR scanner. Five lower-leg muscles were individually assessed for fat and muscle metabolite levels. In the peroneus, soleus and anterior tibialis muscles with non-increased fat levels, PDE/ATP ratios were higher (P < 0.02) compared with controls, whereas in all muscles with increased fat levels PDE/ATP ratios were higher compared with healthy controls (P ≤ 0.05). The Pi /ATP ratio in the peroneus muscles was higher in muscles with increased fat fractions (P = 0.005), and the PCr/ATP ratio was lower in the anterior tibialis muscles with increased fat fractions (P = 0.005). There were no other significant changes in metabolites, but an increase in tissue pH was found in all muscles of the total group of BMD patients in comparison with healthy controls (P < 0.05). These findings suggest that (31) P MRS can be used to detect early changes in individual muscles of BMD patients, which are present before the onset of fatty infiltration. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Modern linear control design a time-domain approach

    CERN Document Server

    Caravani, Paolo

    2013-01-01

    This book offers a compact introduction to modern linear control design.  The simplified overview presented of linear time-domain methodology paves the road for the study of more advanced non-linear techniques. Only rudimentary knowledge of linear systems theory is assumed - no use of Laplace transforms or frequency design tools is required. Emphasis is placed on assumptions and logical implications, rather than abstract completeness; on interpretation and physical meaning, rather than theoretical formalism; on results and solutions, rather than derivation or solvability.  The topics covered include transient performance and stabilization via state or output feedback; disturbance attenuation and robust control; regional eigenvalue assignment and constraints on input or output variables; asymptotic regulation and disturbance rejection. Lyapunov theory and Linear Matrix Inequalities (LMI) are discussed as key design methods. All methods are demonstrated with MATLAB to promote practical use and comprehension. ...

  14. Robust control of uncertain dynamic systems a linear state space approach

    CERN Document Server

    Yedavalli, Rama K

    2014-01-01

    This textbook aims to provide a clear understanding of the various tools of analysis and design for robust stability and performance of uncertain dynamic systems. In model-based control design and analysis, mathematical models can never completely represent the “real world” system that is being modeled, and thus it is imperative to incorporate and accommodate a level of uncertainty into the models. This book directly addresses these issues from a deterministic uncertainty viewpoint and focuses on the interval parameter characterization of uncertain systems. Various tools of analysis and design are presented in a consolidated manner. This volume fills a current gap in published works by explicitly addressing the subject of control of dynamic systems from linear state space framework, namely using a time-domain, matrix-theory based approach. This book also: Presents and formulates the robustness problem in a linear state space model framework Illustrates various systems level methodologies with examples and...

  15. Feedback Linearization approach for Standard and Fault Tolerant control: Application to a Quadrotor UAV Testbed

    International Nuclear Information System (INIS)

    Ghandour, J; Aberkane, S; Ponsart, J-C

    2014-01-01

    In this paper the control problem of a quadrotor vehicle experiencing a rotor failure is investigated. We develop a Feedback linearization approach to design a controller whose task is to make the vehicle performs trajectory following. Then we use the same approach to design a controller whose task is to make the vehicle enter a stable spin around its vertical axis, while retaining zero angular velocities around the other axis when a rotor failure is present. These conditions can be exploited to design a second control loop, which is used to perform trajectory following. The proposed double control loop architecture allows the vehicle to perform both trajectory and roll/pitch control. At last, to test the robustness of the feedback linearization technique, we applied wind to the quadrotor in mid flight

  16. Linear algebra

    CERN Document Server

    Liesen, Jörg

    2015-01-01

    This self-contained textbook takes a matrix-oriented approach to linear algebra and presents a complete theory, including all details and proofs, culminating in the Jordan canonical form and its proof. Throughout the development, the applicability of the results is highlighted. Additionally, the book presents special topics from applied linear algebra including matrix functions, the singular value decomposition, the Kronecker product and linear matrix equations. The matrix-oriented approach to linear algebra leads to a better intuition and a deeper understanding of the abstract concepts, and therefore simplifies their use in real world applications. Some of these applications are presented in detailed examples. In several ‘MATLAB-Minutes’ students can comprehend the concepts and results using computational experiments. Necessary basics for the use of MATLAB are presented in a short introduction. Students can also actively work with the material and practice their mathematical skills in more than 300 exerc...

  17. Performance improvement of shunt active power filter based on non-linear least-square approach

    DEFF Research Database (Denmark)

    Terriche, Yacine

    2018-01-01

    . This paper proposes an improved open loop strategy which is unconditionally stable and flexible. The proposed method which is based on non-linear least square (NLS) approach can extract the fundamental voltage and estimates its phase within only half cycle, even in the presence of odd harmonics and dc offset......). The synchronous reference frame (SRF) approach is widely used for generating the RCC due to its simplicity and computation efficiency. However, the SRF approach needs precise information of the voltage phase which becomes a challenge under adverse grid conditions. A typical solution to answer this need...

  18. Mass Optimization of Battery/Supercapacitors Hybrid Systems Based on a Linear Programming Approach

    Science.gov (United States)

    Fleury, Benoit; Labbe, Julien

    2014-08-01

    The objective of this paper is to show that, on a specific launcher-type mission profile, a 40% gain of mass is expected using a battery/supercapacitors active hybridization instead of a single battery solution. This result is based on the use of a linear programming optimization approach to perform the mass optimization of the hybrid power supply solution.

  19. Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

    2015-01-01

    Aging is associated with an altered regulation of blood flow to contracting skeletal muscle; however, the precise mechanisms remain unclear. We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not you...

  20. State space model extraction of thermohydraulic systems – Part I: A linear graph approach

    International Nuclear Information System (INIS)

    Uren, K.R.; Schoor, G. van

    2013-01-01

    Thermohydraulic simulation codes are increasingly making use of graphical design interfaces. The user can quickly and easily design a thermohydraulic system by placing symbols on the screen resembling system components. These components can then be connected to form a system representation. Such system models may then be used to obtain detailed simulations of the physical system. Usually this kind of simulation models are too complex and not ideal for control system design. Therefore, a need exists for automated techniques to extract lumped parameter models useful for control system design. The goal of this first paper, in a two part series, is to propose a method that utilises a graphical representation of a thermohydraulic system, and a lumped parameter modelling approach, to extract state space models. In this methodology each physical domain of the thermohydraulic system is represented by a linear graph. These linear graphs capture the interaction between all components within and across energy domains – hydraulic, thermal and mechanical. These linear graphs are analysed using a graph-theoretic approach to derive reduced order state space models. These models capture the dominant dynamics of the thermohydraulic system and are ideal for control system design purposes. The proposed state space model extraction method is demonstrated by considering a U-tube system. A non-linear state space model is extracted representing both the hydraulic and thermal domain dynamics of the system. The simulated state space model is compared with a Flownex ® model of the U-tube. Flownex ® is a validated systems thermal-fluid simulation software package. - Highlights: • A state space model extraction methodology based on graph-theoretic concepts. • An energy-based approach to consider multi-domain systems in a common framework. • Allow extraction of transparent (white-box) state space models automatically. • Reduced order models containing only independent state

  1. Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.

    Science.gov (United States)

    Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S

    2016-01-01

    Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Linear and non-linear optics of condensed matter

    International Nuclear Information System (INIS)

    McLean, T.P.

    1977-01-01

    Part I - Linear optics: 1. General introduction. 2. Frequency dependence of epsilon(ω, k vector). 3. Wave-vector dependence of epsilon(ω, k vector). 4. Tensor character of epsilon(ω, k vector). Part II - Non-linear optics: 5. Introduction. 6. A classical theory of non-linear response in one dimension. 7. The generalization to three dimensions. 8. General properties of the polarizability tensors. 9. The phase-matching condition. 10. Propagation in a non-linear dielectric. 11. Second harmonic generation. 12. Coupling of three waves. 13. Materials and their non-linearities. 14. Processes involving energy exchange with the medium. 15. Two-photon absorption. 16. Stimulated Raman effect. 17. Electro-optic effects. 18. Limitations of the approach presented here. (author)

  3. Designing a graph-based approach to landscape ecological assessment of linear infrastructures

    Energy Technology Data Exchange (ETDEWEB)

    Girardet, Xavier, E-mail: xavier.girardet@univ-fcomte.fr; Foltête, Jean-Christophe, E-mail: jean-christophe.foltete@univ-fcomte.fr; Clauzel, Céline, E-mail: celine.clauzel@univ-fcomte.fr

    2013-09-15

    The development of major linear infrastructures contributes to landscape fragmentation and impacts natural habitats and biodiversity in various ways. To anticipate and minimize such impacts, landscape planning needs to be capable of effective strategic environmental assessment (SEA) and of supporting environmental impact assessment (EIA) decisions. To this end, species distribution models (SDMs) are an effective way of making predictive maps of the presence of a given species. In this paper, we propose to combine SDMs and graph-based representation of landscape networks to integrate the potential long-distance effect of infrastructures on species distribution. A diachronic approach, comparing distribution before and after the linear infrastructure is constructed, leads to the design of a species distribution assessment (SDA), taking into account population isolation. The SDA makes it possible (1) to estimate the local variation in probability of presence and (2) to characterize the impact of the infrastructure in terms of global variation in presence and of distance of disturbance. The method is illustrated by assessing the impact of the construction of a high-speed railway line on the distribution of several virtual species in Franche-Comté (France). The study shows the capacity of the SDA to characterize the impact of a linear infrastructure either as a research concern or as a spatial planning challenge. SDAs could be helpful in deciding among several scenarios for linear infrastructure routes or for the location of mitigation measures. -- Highlights: • Graph connectivity metrics were integrated into a species distribution model. • SDM was performed before and after the implementation of linear infrastructure. • The local variation of presence provides spatial indicators of the impact.

  4. Designing a graph-based approach to landscape ecological assessment of linear infrastructures

    International Nuclear Information System (INIS)

    Girardet, Xavier; Foltête, Jean-Christophe; Clauzel, Céline

    2013-01-01

    The development of major linear infrastructures contributes to landscape fragmentation and impacts natural habitats and biodiversity in various ways. To anticipate and minimize such impacts, landscape planning needs to be capable of effective strategic environmental assessment (SEA) and of supporting environmental impact assessment (EIA) decisions. To this end, species distribution models (SDMs) are an effective way of making predictive maps of the presence of a given species. In this paper, we propose to combine SDMs and graph-based representation of landscape networks to integrate the potential long-distance effect of infrastructures on species distribution. A diachronic approach, comparing distribution before and after the linear infrastructure is constructed, leads to the design of a species distribution assessment (SDA), taking into account population isolation. The SDA makes it possible (1) to estimate the local variation in probability of presence and (2) to characterize the impact of the infrastructure in terms of global variation in presence and of distance of disturbance. The method is illustrated by assessing the impact of the construction of a high-speed railway line on the distribution of several virtual species in Franche-Comté (France). The study shows the capacity of the SDA to characterize the impact of a linear infrastructure either as a research concern or as a spatial planning challenge. SDAs could be helpful in deciding among several scenarios for linear infrastructure routes or for the location of mitigation measures. -- Highlights: • Graph connectivity metrics were integrated into a species distribution model. • SDM was performed before and after the implementation of linear infrastructure. • The local variation of presence provides spatial indicators of the impact

  5. Linear versus geometric morphometric approaches for the analysis of head shape dimorphism in lizards.

    Science.gov (United States)

    Fabre, Anne-Claire; Cornette, Raphäel; Huyghe, Katleen; Andrade, Denis V; Herrel, Anthony

    2014-09-01

    Differences between the sexes may arise because of differences in reproductive strategy, with females investing more in traits related to reproductive output and males investing more in traits related to resource holding capacity and territory defence. Sexual dimorphism is widespread in lizards and in many species males and females also differ in head shape. Males typically have bigger heads than females resulting in intersexual differences in bite force. Whereas most studies documenting differences in head dimensions between sexes use linear dimensions, the use of geometric morphometrics has been advocated as more appropriate to characterize such differences. This method may allow the characterization of local shape differences that may have functional consequences, and provides unbiased indicators of shape. Here, we explore whether the two approaches provide similar results in an analyses of head shape in Tupinambis merianae. The Argentine black and white tegu differs dramatically in body size, head size, and bite force between the sexes. However, whether the intersexual differences in bite force are simply the result of differences in head size or whether more subtle modifications (e.g., in muscle insertion areas) are involved remains currently unknown. Based on the crania and mandibles of 19 lizards with known bite force, we show intersexual differences in the shape of the cranium and mandible using both linear and geometric morphometric approaches. Although both types of analyses showed generally similar results for the mandible, this was not the case for the cranium. Geometric morphometric approaches provided better insights into the underlying functional relationships between the cranium and the jaw musculature, as illustrated by shape differences in muscle insertion areas not detected using linear morphometric data. © 2014 Wiley Periodicals, Inc.

  6. Local hyperspectral data multisharpening based on linear/linear-quadratic nonnegative matrix factorization by integrating lidar data

    Science.gov (United States)

    Benhalouche, Fatima Zohra; Karoui, Moussa Sofiane; Deville, Yannick; Ouamri, Abdelaziz

    2015-10-01

    In this paper, a new Spectral-Unmixing-based approach, using Nonnegative Matrix Factorization (NMF), is proposed to locally multi-sharpen hyperspectral data by integrating a Digital Surface Model (DSM) obtained from LIDAR data. In this new approach, the nature of the local mixing model is detected by using the local variance of the object elevations. The hyper/multispectral images are explored using small zones. In each zone, the variance of the object elevations is calculated from the DSM data in this zone. This variance is compared to a threshold value and the adequate linear/linearquadratic spectral unmixing technique is used in the considered zone to independently unmix hyperspectral and multispectral data, using an adequate linear/linear-quadratic NMF-based approach. The obtained spectral and spatial information thus respectively extracted from the hyper/multispectral images are then recombined in the considered zone, according to the selected mixing model. Experiments based on synthetic hyper/multispectral data are carried out to evaluate the performance of the proposed multi-sharpening approach and literature linear/linear-quadratic approaches used on the whole hyper/multispectral data. In these experiments, real DSM data are used to generate synthetic data containing linear and linear-quadratic mixed pixel zones. The DSM data are also used for locally detecting the nature of the mixing model in the proposed approach. Globally, the proposed approach yields good spatial and spectral fidelities for the multi-sharpened data and significantly outperforms the used literature methods.

  7. PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with β2 AR agonists by a natural agent arctigenin.

    Science.gov (United States)

    Fang, R; Cui, Q; Sun, J; Duan, X; Ma, X; Wang, W; Cheng, B; Liu, Y; Hou, Y; Bai, G

    2015-12-01

    Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, β2 adrenergic receptor (β2 AR) agonists bind to the β2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the β2 AR agonist, but the target for this remained elusive. Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PDE4D resulted in cAMP accumulation in human bronchial smooth muscle. The inhibition of PDK1 showed a synergistic function with β2 AR agonists and relaxed the constriction of segregated guinea pig tracheal muscle. The PDK1/Akt/PDE4D axis serves as a novel asthma target, which may benefit airflow obstruction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Scalar-tensor linear inflation

    Energy Technology Data Exchange (ETDEWEB)

    Artymowski, Michał [Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Racioppi, Antonio, E-mail: Michal.Artymowski@uj.edu.pl, E-mail: Antonio.Racioppi@kbfi.ee [National Institute of Chemical Physics and Biophysics, Rävala 10, 10143 Tallinn (Estonia)

    2017-04-01

    We investigate two approaches to non-minimally coupled gravity theories which present linear inflation as attractor solution: a) the scalar-tensor theory approach, where we look for a scalar-tensor theory that would restore results of linear inflation in the strong coupling limit for a non-minimal coupling to gravity of the form of f (φ) R /2; b) the particle physics approach, where we motivate the form of the Jordan frame potential by loop corrections to the inflaton field. In both cases the Jordan frame potentials are modifications of the induced gravity inflationary scenario, but instead of the Starobinsky attractor they lead to linear inflation in the strong coupling limit.

  9. Partial regularity of weak solutions to a PDE system with cubic nonlinearity

    Science.gov (United States)

    Liu, Jian-Guo; Xu, Xiangsheng

    2018-04-01

    In this paper we investigate regularity properties of weak solutions to a PDE system that arises in the study of biological transport networks. The system consists of a possibly singular elliptic equation for the scalar pressure of the underlying biological network coupled to a diffusion equation for the conductance vector of the network. There are several different types of nonlinearities in the system. Of particular mathematical interest is a term that is a polynomial function of solutions and their partial derivatives and this polynomial function has degree three. That is, the system contains a cubic nonlinearity. Only weak solutions to the system have been shown to exist. The regularity theory for the system remains fundamentally incomplete. In particular, it is not known whether or not weak solutions develop singularities. In this paper we obtain a partial regularity theorem, which gives an estimate for the parabolic Hausdorff dimension of the set of possible singular points.

  10. Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy.

    Science.gov (United States)

    Petit, Lolita; Lhériteau, Elsa; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Guihal, Caroline; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

    2012-11-01

    Defects in the β subunit of rod cGMP phosphodiesterase 6 (PDE6β) are associated with autosomal recessive retinitis pigmentosa (RP), a childhood blinding disease with early retinal degeneration and vision loss. To date, there is no treatment for this pathology. The aim of this preclinical study was to test recombinant adeno-associated virus (AAV)-mediated gene addition therapy in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency that strongly resembles the human pathology. A total of eight rcd1 dogs were injected subretinally with AAV2/5RK.cpde6β (n = 4) or AAV2/8RK.cpde6β (n = 4). In vivo and post-mortem morphological analysis showed a significant preservation of the retinal structure in transduced areas of both AAV2/5RK.cpde6β- and AAV2/8RK.cpde6β-treated retinas. Moreover, substantial rod-derived electroretinography (ERG) signals were recorded as soon as 1 month postinjection (35% of normal eyes) and remained stable for at least 18 months (the duration of the study) in treated eyes. Rod-responses were undetectable in untreated contralateral eyes. Most importantly, dim-light vision was restored in all treated rcd1 dogs. These results demonstrate for the first time that gene therapy effectively restores long-term retinal function and vision in a large animal model of autosomal recessive rod-cone dystrophy, and provide great promise for human treatment.

  11. A Dynamic Linear Modeling Approach to Public Policy Change

    DEFF Research Database (Denmark)

    Loftis, Matthew; Mortensen, Peter Bjerre

    2017-01-01

    Theories of public policy change, despite their differences, converge on one point of strong agreement. The relationship between policy and its causes can and does change over time. This consensus yields numerous empirical implications, but our standard analytical tools are inadequate for testing...... them. As a result, the dynamic and transformative relationships predicted by policy theories have been left largely unexplored in time-series analysis of public policy. This paper introduces dynamic linear modeling (DLM) as a useful statistical tool for exploring time-varying relationships in public...... policy. The paper offers a detailed exposition of the DLM approach and illustrates its usefulness with a time series analysis of U.S. defense policy from 1957-2010. The results point the way for a new attention to dynamics in the policy process and the paper concludes with a discussion of how...

  12. Gene selection for the reconstruction of stem cell differentiation trees: a linear programming approach.

    Science.gov (United States)

    Ghadie, Mohamed A; Japkowicz, Nathalie; Perkins, Theodore J

    2015-08-15

    Stem cell differentiation is largely guided by master transcriptional regulators, but it also depends on the expression of other types of genes, such as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc. Traditional approaches to understanding gene expression patterns across multiple conditions, such as principal components analysis or K-means clustering, can group cell types based on gene expression, but they do so without knowledge of the differentiation hierarchy. Hierarchical clustering can organize cell types into a tree, but in general this tree is different from the differentiation hierarchy itself. Given the differentiation hierarchy and gene expression data at each node, we construct a weighted Euclidean distance metric such that the minimum spanning tree with respect to that metric is precisely the given differentiation hierarchy. We provide a set of linear constraints that are provably sufficient for the desired construction and a linear programming approach to identify sparse sets of weights, effectively identifying genes that are most relevant for discriminating different parts of the tree. We apply our method to microarray gene expression data describing 38 cell types in the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses just 175 genes. However, we find that there are many alternative sets of weights that satisfy the linear constraints. Thus, in the style of random-forest training, we also construct metrics based on random subsets of the genes and compare them to the metric of 175 genes. We then report on the selected genes and their biological functions. Our approach offers a new way to identify genes that may have important roles in stem cell differentiation. tperkins@ohri.ca Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. A linear evolution for non-linear dynamics and correlations in realistic nuclei

    International Nuclear Information System (INIS)

    Levin, E.; Lublinsky, M.

    2004-01-01

    A new approach to high energy evolution based on a linear equation for QCD generating functional is developed. This approach opens a possibility for systematic study of correlations inside targets, and, in particular, inside realistic nuclei. Our results are presented as three new equations. The first one is a linear equation for QCD generating functional (and for scattering amplitude) that sums the 'fan' diagrams. For the amplitude this equation is equivalent to the non-linear Balitsky-Kovchegov equation. The second equation is a generalization of the Balitsky-Kovchegov non-linear equation to interactions with realistic nuclei. It includes a new correlation parameter which incorporates, in a model-dependent way, correlations inside the nuclei. The third equation is a non-linear equation for QCD generating functional (and for scattering amplitude) that in addition to the 'fan' diagrams sums the Glauber-Mueller multiple rescatterings

  14. An linear matrix inequality approach to global synchronisation of non-parameter perturbations of multi-delay Hopfield neural network

    International Nuclear Information System (INIS)

    Shao Hai-Jian; Cai Guo-Liang; Wang Hao-Xiang

    2010-01-01

    In this study, a successful linear matrix inequality approach is used to analyse a non-parameter perturbation of multi-delay Hopfield neural network by constructing an appropriate Lyapunov-Krasovskii functional. This paper presents the comprehensive discussion of the approach and also extensive applications

  15. Linearized dynamical approach to current algebra

    International Nuclear Information System (INIS)

    Scadron, M.D.

    1995-07-01

    We study the original motivations searching for a nonlinear chiral Lagrangian to replace the linear sigma model while manifesting all the successful properties of current algebra and partial conservation of axial currents (PCAC). (author). 26 refs

  16. Quantitative Approach to Failure Mode and Effect Analysis for Linear Accelerator Quality Assurance

    Energy Technology Data Exchange (ETDEWEB)

    O' Daniel, Jennifer C., E-mail: jennifer.odaniel@duke.edu; Yin, Fang-Fang

    2017-05-01

    Purpose: To determine clinic-specific linear accelerator quality assurance (QA) TG-142 test frequencies, to maximize physicist time efficiency and patient treatment quality. Methods and Materials: A novel quantitative approach to failure mode and effect analysis is proposed. Nine linear accelerator-years of QA records provided data on failure occurrence rates. The severity of test failure was modeled by introducing corresponding errors into head and neck intensity modulated radiation therapy treatment plans. The relative risk of daily linear accelerator QA was calculated as a function of frequency of test performance. Results: Although the failure severity was greatest for daily imaging QA (imaging vs treatment isocenter and imaging positioning/repositioning), the failure occurrence rate was greatest for output and laser testing. The composite ranking results suggest that performing output and lasers tests daily, imaging versus treatment isocenter and imaging positioning/repositioning tests weekly, and optical distance indicator and jaws versus light field tests biweekly would be acceptable for non-stereotactic radiosurgery/stereotactic body radiation therapy linear accelerators. Conclusions: Failure mode and effect analysis is a useful tool to determine the relative importance of QA tests from TG-142. Because there are practical time limitations on how many QA tests can be performed, this analysis highlights which tests are the most important and suggests the frequency of testing based on each test's risk priority number.

  17. Quantitative Approach to Failure Mode and Effect Analysis for Linear Accelerator Quality Assurance.

    Science.gov (United States)

    O'Daniel, Jennifer C; Yin, Fang-Fang

    2017-05-01

    To determine clinic-specific linear accelerator quality assurance (QA) TG-142 test frequencies, to maximize physicist time efficiency and patient treatment quality. A novel quantitative approach to failure mode and effect analysis is proposed. Nine linear accelerator-years of QA records provided data on failure occurrence rates. The severity of test failure was modeled by introducing corresponding errors into head and neck intensity modulated radiation therapy treatment plans. The relative risk of daily linear accelerator QA was calculated as a function of frequency of test performance. Although the failure severity was greatest for daily imaging QA (imaging vs treatment isocenter and imaging positioning/repositioning), the failure occurrence rate was greatest for output and laser testing. The composite ranking results suggest that performing output and lasers tests daily, imaging versus treatment isocenter and imaging positioning/repositioning tests weekly, and optical distance indicator and jaws versus light field tests biweekly would be acceptable for non-stereotactic radiosurgery/stereotactic body radiation therapy linear accelerators. Failure mode and effect analysis is a useful tool to determine the relative importance of QA tests from TG-142. Because there are practical time limitations on how many QA tests can be performed, this analysis highlights which tests are the most important and suggests the frequency of testing based on each test's risk priority number. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.

    Science.gov (United States)

    Xia, Wenmin; Pessentheiner, Ariane R; Hofer, Dina C; Amor, Melina; Schreiber, Renate; Schoiswohl, Gabriele; Eichmann, Thomas O; Walenta, Evelyn; Itariu, Bianca; Prager, Gerhard; Hackl, Hubert; Stulnig, Thomas; Kratky, Dagmar; Rülicke, Thomas; Bogner-Strauss, Juliane G

    2018-05-15

    Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/β-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis. In vitro data reveal that ABHD15 associates with and stabilizes phosphodiesterase 3B (PDE3B). Accordingly, PDE3B expression is decreased in the WAT of Abhd15-KO mice, mechanistically explaining increased protein kinase A (PKA) activity, hormone-sensitive lipase (HSL) phosphorylation, and undiminished FA release upon insulin signaling. Ultimately, Abhd15-KO mice develop insulin resistance. Notably, ABHD15 expression is decreased in humans with obesity and diabetes compared to humans with obesity and normal glucose tolerance, identifying ABHD15 as a potential therapeutic target to mitigate insulin resistance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram

    NARCIS (Netherlands)

    Dijkhuizen, B; deMonchy, JGR; Dubois, AEJ; Gerritsen, J; Kauffman, HF

    We quantitatively determined whether the selective phosphodiesterase (PDE) inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L-selectin on platelet-activating factor (PAF)-stimulated human neutrophils and eosinophils in vitro. Incubations were performed in human whole blood

  20. Mixed H∞ and passive control for linear switched systems via hybrid control approach

    Science.gov (United States)

    Zheng, Qunxian; Ling, Youzhu; Wei, Lisheng; Zhang, Hongbin

    2018-03-01

    This paper investigates the mixed H∞ and passive control problem for linear switched systems based on a hybrid control strategy. To solve this problem, first, a new performance index is proposed. This performance index can be viewed as the mixed weighted H∞ and passivity performance. Then, the hybrid controllers are used to stabilise the switched systems. The hybrid controllers consist of dynamic output-feedback controllers for every subsystem and state updating controllers at the switching instant. The design of state updating controllers not only depends on the pre-switching subsystem and the post-switching subsystem, but also depends on the measurable output signal. The hybrid controllers proposed in this paper can include some existing ones as special cases. Combine the multiple Lyapunov functions approach with the average dwell time technique, new sufficient conditions are obtained. Under the new conditions, the closed-loop linear switched systems are globally uniformly asymptotically stable with a mixed H∞ and passivity performance index. Moreover, the desired hybrid controllers can be constructed by solving a set of linear matrix inequalities. Finally, a numerical example and a practical example are given.

  1. Adaptive [theta]-methods for pricing American options

    Science.gov (United States)

    Khaliq, Abdul Q. M.; Voss, David A.; Kazmi, Kamran

    2008-12-01

    We develop adaptive [theta]-methods for solving the Black-Scholes PDE for American options. By adding a small, continuous term, the Black-Scholes PDE becomes an advection-diffusion-reaction equation on a fixed spatial domain. Standard implementation of [theta]-methods would require a Newton-type iterative procedure at each time step thereby increasing the computational complexity of the methods. Our linearly implicit approach avoids such complications. We establish a general framework under which [theta]-methods satisfy a discrete version of the positivity constraint characteristic of American options, and numerically demonstrate the sensitivity of the constraint. The positivity results are established for the single-asset and independent two-asset models. In addition, we have incorporated and analyzed an adaptive time-step control strategy to increase the computational efficiency. Numerical experiments are presented for one- and two-asset American options, using adaptive exponential splitting for two-asset problems. The approach is compared with an iterative solution of the two-asset problem in terms of computational efficiency.

  2. Dynamics of unsymmetric piecewise-linear/non-linear systems using finite elements in time

    Science.gov (United States)

    Wang, Yu

    1995-08-01

    The dynamic response and stability of a single-degree-of-freedom system with unsymmetric piecewise-linear/non-linear stiffness are analyzed using the finite element method in the time domain. Based on a Hamilton's weak principle, this method provides a simple and efficient approach for predicting all possible fundamental and sub-periodic responses. The stability of the steady state response is determined by using Floquet's theory without any special effort for calculating transition matrices. This method is applied to a number of examples, demonstrating its effectiveness even for a strongly non-linear problem involving both clearance and continuous stiffness non-linearities. Close agreement is found between available published findings and the predictions of the finite element in time approach, which appears to be an efficient and reliable alternative technique for non-linear dynamic response and stability analysis of periodic systems.

  3. Valid statistical approaches for analyzing sholl data: Mixed effects versus simple linear models.

    Science.gov (United States)

    Wilson, Machelle D; Sethi, Sunjay; Lein, Pamela J; Keil, Kimberly P

    2017-03-01

    The Sholl technique is widely used to quantify dendritic morphology. Data from such studies, which typically sample multiple neurons per animal, are often analyzed using simple linear models. However, simple linear models fail to account for intra-class correlation that occurs with clustered data, which can lead to faulty inferences. Mixed effects models account for intra-class correlation that occurs with clustered data; thus, these models more accurately estimate the standard deviation of the parameter estimate, which produces more accurate p-values. While mixed models are not new, their use in neuroscience has lagged behind their use in other disciplines. A review of the published literature illustrates common mistakes in analyses of Sholl data. Analysis of Sholl data collected from Golgi-stained pyramidal neurons in the hippocampus of male and female mice using both simple linear and mixed effects models demonstrates that the p-values and standard deviations obtained using the simple linear models are biased downwards and lead to erroneous rejection of the null hypothesis in some analyses. The mixed effects approach more accurately models the true variability in the data set, which leads to correct inference. Mixed effects models avoid faulty inference in Sholl analysis of data sampled from multiple neurons per animal by accounting for intra-class correlation. Given the widespread practice in neuroscience of obtaining multiple measurements per subject, there is a critical need to apply mixed effects models more widely. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Return-Volatility Relationship: Insights from Linear and Non-Linear Quantile Regression

    NARCIS (Netherlands)

    D.E. Allen (David); A.K. Singh (Abhay); R.J. Powell (Robert); M.J. McAleer (Michael); J. Taylor (James); L. Thomas (Lyn)

    2013-01-01

    textabstractThe purpose of this paper is to examine the asymmetric relationship between price and implied volatility and the associated extreme quantile dependence using linear and non linear quantile regression approach. Our goal in this paper is to demonstrate that the relationship between the

  5. Linear and Generalized Linear Mixed Models and Their Applications

    CERN Document Server

    Jiang, Jiming

    2007-01-01

    This book covers two major classes of mixed effects models, linear mixed models and generalized linear mixed models, and it presents an up-to-date account of theory and methods in analysis of these models as well as their applications in various fields. The book offers a systematic approach to inference about non-Gaussian linear mixed models. Furthermore, it has included recently developed methods, such as mixed model diagnostics, mixed model selection, and jackknife method in the context of mixed models. The book is aimed at students, researchers and other practitioners who are interested

  6. Linear differential equations to solve nonlinear mechanical problems: A novel approach

    OpenAIRE

    Nair, C. Radhakrishnan

    2004-01-01

    Often a non-linear mechanical problem is formulated as a non-linear differential equation. A new method is introduced to find out new solutions of non-linear differential equations if one of the solutions of a given non-linear differential equation is known. Using the known solution of the non-linear differential equation, linear differential equations are set up. The solutions of these linear differential equations are found using standard techniques. Then the solutions of the linear differe...

  7. Linear models in matrix form a hands-on approach for the behavioral sciences

    CERN Document Server

    Brown, Jonathon D

    2014-01-01

    This textbook is an approachable introduction to statistical analysis using matrix algebra. Prior knowledge of matrix algebra is not necessary. Advanced topics are easy to follow through analyses that were performed on an open-source spreadsheet using a few built-in functions. These topics include ordinary linear regression, as well as maximum likelihood estimation, matrix decompositions, nonparametric smoothers and penalized cubic splines. Each data set (1) contains a limited number of observations to encourage readers to do the calculations themselves, and (2) tells a coherent story based on statistical significance and confidence intervals. In this way, students will learn how the numbers were generated and how they can be used to make cogent arguments about everyday matters. This textbook is designed for use in upper level undergraduate courses or first year graduate courses. The first chapter introduces students to linear equations, then covers matrix algebra, focusing on three essential operations: sum ...

  8. A frequency domain linearized Navier-Stokes equations approach to acoustic propagation in flow ducts with sharp edges.

    Science.gov (United States)

    Kierkegaard, Axel; Boij, Susann; Efraimsson, Gunilla

    2010-02-01

    Acoustic wave propagation in flow ducts is commonly modeled with time-domain non-linear Navier-Stokes equation methodologies. To reduce computational effort, investigations of a linearized approach in frequency domain are carried out. Calculations of sound wave propagation in a straight duct are presented with an orifice plate and a mean flow present. Results of transmission and reflections at the orifice are presented on a two-port scattering matrix form and are compared to measurements with good agreement. The wave propagation is modeled with a frequency domain linearized Navier-Stokes equation methodology. This methodology is found to be efficient for cases where the acoustic field does not alter the mean flow field, i.e., when whistling does not occur.

  9. Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats.

    Directory of Open Access Journals (Sweden)

    Abdallah Ahnaou

    Full Text Available Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A and activation of metabotropic glutamate receptor (mGluR2 signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1 model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA antagonist phencyclidine (PCP; 2 confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3 evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not.

  10. Towards Automated Binding Affinity Prediction Using an Iterative Linear Interaction Energy Approach

    Directory of Open Access Journals (Sweden)

    C. Ruben Vosmeer

    2014-01-01

    Full Text Available Binding affinity prediction of potential drugs to target and off-target proteins is an essential asset in drug development. These predictions require the calculation of binding free energies. In such calculations, it is a major challenge to properly account for both the dynamic nature of the protein and the possible variety of ligand-binding orientations, while keeping computational costs tractable. Recently, an iterative Linear Interaction Energy (LIE approach was introduced, in which results from multiple simulations of a protein-ligand complex are combined into a single binding free energy using a Boltzmann weighting-based scheme. This method was shown to reach experimental accuracy for flexible proteins while retaining the computational efficiency of the general LIE approach. Here, we show that the iterative LIE approach can be used to predict binding affinities in an automated way. A workflow was designed using preselected protein conformations, automated ligand docking and clustering, and a (semi-automated molecular dynamics simulation setup. We show that using this workflow, binding affinities of aryloxypropanolamines to the malleable Cytochrome P450 2D6 enzyme can be predicted without a priori knowledge of dominant protein-ligand conformations. In addition, we provide an outlook for an approach to assess the quality of the LIE predictions, based on simulation outcomes only.

  11. An Instructional Note on Linear Programming--A Pedagogically Sound Approach.

    Science.gov (United States)

    Mitchell, Richard

    1998-01-01

    Discusses the place of linear programming in college curricula and the advantages of using linear-programming software. Lists important characteristics of computer software used in linear programming for more effective teaching and learning. (ASK)

  12. Controller design approach based on linear programming.

    Science.gov (United States)

    Tanaka, Ryo; Shibasaki, Hiroki; Ogawa, Hiromitsu; Murakami, Takahiro; Ishida, Yoshihisa

    2013-11-01

    This study explains and demonstrates the design method for a control system with a load disturbance observer. Observer gains are determined by linear programming (LP) in terms of the Routh-Hurwitz stability criterion and the final-value theorem. In addition, the control model has a feedback structure, and feedback gains are determined to be the linear quadratic regulator. The simulation results confirmed that compared with the conventional method, the output estimated by our proposed method converges to a reference input faster when a load disturbance is added to a control system. In addition, we also confirmed the effectiveness of the proposed method by performing an experiment with a DC motor. © 2013 ISA. Published by ISA. All rights reserved.

  13. Solving non-linear Horn clauses using a linear Horn clause solver

    DEFF Research Database (Denmark)

    Kafle, Bishoksan; Gallagher, John Patrick; Ganty, Pierre

    2016-01-01

    In this paper we show that checking satisfiability of a set of non-linear Horn clauses (also called a non-linear Horn clause program) can be achieved using a solver for linear Horn clauses. We achieve this by interleaving a program transformation with a satisfiability checker for linear Horn...... clauses (also called a solver for linear Horn clauses). The program transformation is based on the notion of tree dimension, which we apply to a set of non-linear clauses, yielding a set whose derivation trees have bounded dimension. Such a set of clauses can be linearised. The main algorithm...... dimension. We constructed a prototype implementation of this approach and performed some experiments on a set of verification problems, which shows some promise....

  14. The Bayes linear approach to inference and decision-making for a reliability programme

    International Nuclear Information System (INIS)

    Goldstein, Michael; Bedford, Tim

    2007-01-01

    In reliability modelling it is conventional to build sophisticated models of the probabilistic behaviour of the component lifetimes in a system in order to deduce information about the probabilistic behaviour of the system lifetime. Decision modelling of the reliability programme requires a priori, therefore, an even more sophisticated set of models in order to capture the evidence the decision maker believes may be obtained from different types of data acquisition. Bayes linear analysis is a methodology that uses expectation rather than probability as the fundamental expression of uncertainty. By working only with expected values, a simpler level of modelling is needed as compared to full probability models. In this paper we shall consider the Bayes linear approach to the estimation of a mean time to failure MTTF of a component. The model built will take account of the variance in our estimate of the MTTF, based on a variety of sources of information

  15. A Genetic-Algorithms-Based Approach for Programming Linear and Quadratic Optimization Problems with Uncertainty

    Directory of Open Access Journals (Sweden)

    Weihua Jin

    2013-01-01

    Full Text Available This paper proposes a genetic-algorithms-based approach as an all-purpose problem-solving method for operation programming problems under uncertainty. The proposed method was applied for management of a municipal solid waste treatment system. Compared to the traditional interactive binary analysis, this approach has fewer limitations and is able to reduce the complexity in solving the inexact linear programming problems and inexact quadratic programming problems. The implementation of this approach was performed using the Genetic Algorithm Solver of MATLAB (trademark of MathWorks. The paper explains the genetic-algorithms-based method and presents details on the computation procedures for each type of inexact operation programming problems. A comparison of the results generated by the proposed method based on genetic algorithms with those produced by the traditional interactive binary analysis method is also presented.

  16. Moving-Horizon Modulating Functions-Based Algorithm for Online Source Estimation in a First Order Hyperbolic PDE

    KAUST Repository

    Asiri, Sharefa M.; Elmetennani, Shahrazed; Laleg-Kirati, Taous-Meriem

    2017-01-01

    In this paper, an on-line estimation algorithm of the source term in a first order hyperbolic PDE is proposed. This equation describes heat transport dynamics in concentrated solar collectors where the source term represents the received energy. This energy depends on the solar irradiance intensity and the collector characteristics affected by the environmental changes. Control strategies are usually used to enhance the efficiency of heat production; however, these strategies often depend on the source term which is highly affected by the external working conditions. Hence, efficient source estimation methods are required. The proposed algorithm is based on modulating functions method where a moving horizon strategy is introduced. Numerical results are provided to illustrate the performance of the proposed estimator in open and closed loops.

  17. Moving-Horizon Modulating Functions-Based Algorithm for Online Source Estimation in a First Order Hyperbolic PDE

    KAUST Repository

    Asiri, Sharefa M.

    2017-08-22

    In this paper, an on-line estimation algorithm of the source term in a first order hyperbolic PDE is proposed. This equation describes heat transport dynamics in concentrated solar collectors where the source term represents the received energy. This energy depends on the solar irradiance intensity and the collector characteristics affected by the environmental changes. Control strategies are usually used to enhance the efficiency of heat production; however, these strategies often depend on the source term which is highly affected by the external working conditions. Hence, efficient source estimation methods are required. The proposed algorithm is based on modulating functions method where a moving horizon strategy is introduced. Numerical results are provided to illustrate the performance of the proposed estimator in open and closed loops.

  18. A non-linear state space approach to model groundwater fluctuations

    NARCIS (Netherlands)

    Berendrecht, W.L.; Heemink, A.W.; Geer, F.C. van; Gehrels, J.C.

    2006-01-01

    A non-linear state space model is developed for describing groundwater fluctuations. Non-linearity is introduced by modeling the (unobserved) degree of water saturation of the root zone. The non-linear relations are based on physical concepts describing the dependence of both the actual

  19. Exercise training improves erectile dysfunction (ED) in patients with metabolic syndrome on phosphodiesterase-5 (PDE-5) inhibitors.

    Science.gov (United States)

    Maresca, Luigi; D'Agostino, Mariantonietta; Castaldo, Luigi; Vitelli, Alessandra; Mancini, Maria; Torella, Giorgio; Lucci, Rosa; Albano, Giovanna; Del Forno, Domenico; Ferro, Matteo; Altieri, Vincenzo; Giallauria, Francesco; Vigorito, Carlo

    2013-12-01

    Erectile dysfunction (ED) affects about 50% of males aged 40-70 years old. ED shares with atherosclerotic disease several common risk factors; therefore, it may be considered a surrogate marker of atherosclerosis. Since phosphodiesterase-5 inhibitors are well known pharmacologic agents capable of significant improvement in ED, we designed this study to evaluate whether exercise training is of added value in patients with ED who are already on PDE-5 inhibitors. We recruited 20 male patients affected by ED with metabolic syndrome. At baseline, all patients underwent Cardio-Pulmonary Exercise Testing (CPET) and the International Index of Erectile Function (IIEF) test. After the initial evaluation, patients were subdivided into two groups: tadalafil group (group T, n = 10), who were maintained only on tadalafil therapy, and a tadalafil/exercise training group (T/E group, n = 10) who continued tadalafil but in addition underwent a2-month structured exercise training program. Basal anthropometric characteristics of study population showed no significant differences. Although both-groups showed at 2 months an improvement of the IIEF score, this was more evident in the T/E group (T group: 11.2 vs 14.2, P = 0.02; T/E group: 10.8 vs 20.1, P exercise (VO(2peak)) only in the T/E group patients (T group: 13.63 +/- 2.03 vs 14.24 +/- 2.98 mL/kg/min; P = 0.521; T/E group: 13.41 +/- 2.97 vs 16.58 +/- 3.17 mL/kg/min; P = 0.006). A significant correlation was found between the changes in VO(2peak) and the modifications in IIEF score (r = 0.575; P = 0.001). Exercise training in ED patients treated with PDE-5 inhibitors is of added value since further improves ED, as evaluated by IIEF score, and increases functional capacity.

  20. A Fuzzy Linear Programming Approach for Aggregate Production Planning

    DEFF Research Database (Denmark)

    Iris, Cagatay; Cevikcan, Emre

    2014-01-01

    a mathematical programming framework for aggregate production planning problem under imprecise data environment. After providing background information about APP problem, together with fuzzy linear programming, the fuzzy linear programming model of APP is solved on an illustrative example for different a...

  1. Parallelized Three-Dimensional Resistivity Inversion Using Finite Elements And Adjoint State Methods

    Science.gov (United States)

    Schaa, Ralf; Gross, Lutz; Du Plessis, Jaco

    2015-04-01

    The resistivity method is one of the oldest geophysical exploration methods, which employs one pair of electrodes to inject current into the ground and one or more pairs of electrodes to measure the electrical potential difference. The potential difference is a non-linear function of the subsurface resistivity distribution described by an elliptic partial differential equation (PDE) of the Poisson type. Inversion of measured potentials solves for the subsurface resistivity represented by PDE coefficients. With increasing advances in multichannel resistivity acquisition systems (systems with more than 60 channels and full waveform recording are now emerging), inversion software require efficient storage and solver algorithms. We developed the finite element solver Escript, which provides a user-friendly programming environment in Python to solve large-scale PDE-based problems (see https://launchpad.net/escript-finley). Using finite elements, highly irregular shaped geology and topography can readily be taken into account. For the 3D resistivity problem, we have implemented the secondary potential approach, where the PDE is decomposed into a primary potential caused by the source current and the secondary potential caused by changes in subsurface resistivity. The primary potential is calculated analytically, and the boundary value problem for the secondary potential is solved using nodal finite elements. This approach removes the singularity caused by the source currents and provides more accurate 3D resistivity models. To solve the inversion problem we apply a 'first optimize then discretize' approach using the quasi-Newton scheme in form of the limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) method (see Gross & Kemp 2013). The evaluation of the cost function requires the solution of the secondary potential PDE for each source current and the solution of the corresponding adjoint-state PDE for the cost function gradients with respect to the subsurface

  2. Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D)

    OpenAIRE

    Gurney, Mark E.; Cogram, Patricia; Deacon, Robert M; Rex, Christopher; Tranfaglia, Michael

    2017-01-01

    Fragile-X syndrome (FXS) patients display intellectual disability and autism spectrum disorder due to silencing of the X-linked, fragile-X mental retardation-1 (FMR1) gene. Dysregulation of cAMP metabolism is a consistent finding in patients and in the mouse and fly FXS models. We therefore explored if BPN14770, a prototypic phosphodiesterase-4D negative allosteric modulator (PDE4D-NAM) in early human clinical trials, might provide therapeutic benefit in the mouse FXS model. Daily treatment o...

  3. An Introduction to the Hybrid Approach of Neural Networks and the Linear Regression Model : An Illustration in the Hedonic Pricing Model of Building Costs

    OpenAIRE

    浅野, 美代子; マーコ, ユー K.W.

    2007-01-01

    This paper introduces the hybrid approach of neural networks and linear regression model proposed by Asano and Tsubaki (2003). Neural networks are often credited with its superiority in data consistency whereas the linear regression model provides simple interpretation of the data enabling researchers to verify their hypotheses. The hybrid approach aims at combing the strengths of these two well-established statistical methods. A step-by-step procedure for performing the hybrid approach is pr...

  4. Energetic Variational Approach to Multi-Component Fluid Flows

    Science.gov (United States)

    Kirshtein, Arkadz; Liu, Chun; Brannick, James

    2017-11-01

    In this talk I will introduce the systematic energetic variational approach for dissipative systems applied to multi-component fluid flows. These variational approaches are motivated by the seminal works of Rayleigh and Onsager. The advantage of this approach is that we have to postulate only energy law and some kinematic relations based on fundamental physical principles. The method gives a clear, quick and consistent way to derive the PDE system. I will compare different approaches to three-component flows using diffusive interface method and discuss their advantages and disadvantages. The diffusive interface method is an approach for modeling interactions among complex substances. The main idea behind this method is to introduce phase field labeling functions in order to model the contact line by smooth change from one type of material to another. The work of Arkadz Kirshtein and Chun Liu is partially supported by NSF Grants DMS-141200 and DMS-1216938.

  5. Linear algebra

    CERN Document Server

    Said-Houari, Belkacem

    2017-01-01

    This self-contained, clearly written textbook on linear algebra is easily accessible for students. It begins with the simple linear equation and generalizes several notions from this equation for the system of linear equations and introduces the main ideas using matrices. It then offers a detailed chapter on determinants and introduces the main ideas with detailed proofs. The third chapter introduces the Euclidean spaces using very simple geometric ideas and discusses various major inequalities and identities. These ideas offer a solid basis for understanding general Hilbert spaces in functional analysis. The following two chapters address general vector spaces, including some rigorous proofs to all the main results, and linear transformation: areas that are ignored or are poorly explained in many textbooks. Chapter 6 introduces the idea of matrices using linear transformation, which is easier to understand than the usual theory of matrices approach. The final two chapters are more advanced, introducing t...

  6. Occupational radiation protection around medical linear accelerators: measurements and semi-analytical approaches

    International Nuclear Information System (INIS)

    Donadille, L.; Derreumaux, S.; Mantione, J.; Robbes, I.; Trompier, F.; Amgarou, K.; Asselineau, B.; Martin, A.

    2008-01-01

    Full text: X-rays produced by high-energy (larger than 6 MeV) medical electron linear accelerators create secondary neutron radiation fields mainly by photonuclear reactions inside the materials of the accelerator head, the patient and the walls of the therapy room. Numerous papers were devoted to the study of neutron production in medical linear accelerators and resulting decay of activation products. However, data associated to doses delivered to workers in treatment conditions are scarce. In France, there are more than 350 external radiotherapy facilities representing almost all types of techniques and designs. IRSN carried out a measurement campaign in order to investigate the variation of the occupational dose according the different encountered situations. Six installations were investigated, associated with the main manufacturers (Varian, Elekta, General Electrics, Siemens), for several nominal energies, conventional and IMRT techniques, and bunker designs. Measurements were carried out separately for neutron and photon radiation fields, and for radiation associated with the decay of the activation products, by means of radiometers, tissue-equivalent proportional counters and spectrometers (neutron and photon spectrometry). They were performed at the positions occupied by the workers, i.e. outside the bunker during treatments, inside between treatments. Measurements have been compared to published data. In addition, semi-empirical analytical approaches recommended by international protocols were used to estimate doses inside and outside the bunkers. The results obtained by both approaches were compared and analysed. The annual occupational effective dose was estimated to about 1 mSv, including more than 50 % associated with the decay of activation products and less than 10 % due to direct exposure to leakage neutrons produced during treatments. (author)

  7. Time scaling internal state predictive control of a solar plant

    Energy Technology Data Exchange (ETDEWEB)

    Silva, R.N. [DEE-FCT/UNL, Caparica (Portugal); Rato, L.M. [INESC-ID/University, Evora (Portugal); Lemos, J.M. [INESC-ID/IST, Lisboa (Portugal)

    2003-12-01

    The control of a distributed collector solar field is addressed in this work, exploiting the plant's transport characteristic. The plant is modeled by a hyperbolic type partial differential equation (PDE) where the transport speed is the manipulated flow, i.e. the controller output. The model has an external distributed source, which is the solar radiation captured along the collector, approximated to depend only of time. From the solution of the PDE, a linear discrete state space model is obtained by using time-scaling and the redefinition of the control input. This method allows overcoming the dependency of the time constants with the operating point. A model-based predictive adaptive controller is derived with the internal temperature distribution estimated with a state observer. Experimental results at the solar power plant are presented, illustrating the advantages of the approach under consideration. (author)

  8. Linear algebraic approach to electron-molecule collisions

    International Nuclear Information System (INIS)

    Schneider, B.I.; Collins, L.A.

    1983-01-01

    The various levels of sophistication of the linear algebraic method are discussed and its application to electron-molecule collisions of H 2 , N 2 LiH, LiF and HCl is described. 13 references, 2 tables

  9. Design of Linear Accelerator (LINAC) tanks for proton therapy via Particle Swarm Optimization (PSO) and Genetic Algorithm (GA) approaches

    International Nuclear Information System (INIS)

    Castellano, T.; De Palma, L.; Laneve, D.; Strippoli, V.; Cuccovilllo, A.; Prudenzano, F.; Dimiccoli, V.; Losito, O.; Prisco, R.

    2015-01-01

    A homemade computer code for designing a Side- Coupled Linear Accelerator (SCL) is written. It integrates a simplified model of SCL tanks with the Particle Swarm Optimization (PSO) algorithm. The computer code main aim is to obtain useful guidelines for the design of Linear Accelerator (LINAC) resonant cavities. The design procedure, assisted via the aforesaid approach seems very promising, allowing future improvements towards the optimization of actual accelerating geometries. (authors)

  10. Design of Linear Accelerator (LINAC) tanks for proton therapy via Particle Swarm Optimization (PSO) and Genetic Algorithm (GA) approaches

    Energy Technology Data Exchange (ETDEWEB)

    Castellano, T.; De Palma, L.; Laneve, D.; Strippoli, V.; Cuccovilllo, A.; Prudenzano, F. [Electrical and Information Engineering Department (DEI), Polytechnic Institute of Bari, 4 Orabona Street, CAP 70125, Bari, (Italy); Dimiccoli, V.; Losito, O.; Prisco, R. [ITEL Telecomunicazioni, 39 Labriola Street, CAP 70037, Ruvo di Puglia, Bari, (Italy)

    2015-07-01

    A homemade computer code for designing a Side- Coupled Linear Accelerator (SCL) is written. It integrates a simplified model of SCL tanks with the Particle Swarm Optimization (PSO) algorithm. The computer code main aim is to obtain useful guidelines for the design of Linear Accelerator (LINAC) resonant cavities. The design procedure, assisted via the aforesaid approach seems very promising, allowing future improvements towards the optimization of actual accelerating geometries. (authors)

  11. Power System Event Ranking Using a New Linear Parameter-Varying Modeling with a Wide Area Measurement System-Based Approach

    Directory of Open Access Journals (Sweden)

    Mohammad Bagher Abolhasani Jabali

    2017-07-01

    Full Text Available Detecting critical power system events for Dynamic Security Assessment (DSA is required for reliability improvement. The approach proposed in this paper investigates the effects of events on dynamic behavior during nonlinear system response while common approaches use steady-state conditions after events. This paper presents some new and enhanced indices for event ranking based on time-domain simulation and polytopic linear parameter-varying (LPV modeling of a power system. In the proposed approach, a polytopic LPV representation is generated via linearization about some points of the nonlinear dynamic behavior of power system using wide-area measurement system (WAMS concepts and then event ranking is done based on the frequency response of the system models on the vertices. Therefore, the nonlinear behaviors of the system in the time of fault occurrence are considered for events ranking. The proposed algorithm is applied to a power system using nonlinear simulation. The comparison of the results especially in different fault conditions shows the advantages of the proposed approach and indices.

  12. Cardiac output by Doppler echocardiography in the premature baboon: Comparison with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Kinsella, J.P.; Morrow, W.R.; Gerstmann, D.R.; Taylor, A.F.; deLemos, R.A.

    1991-01-01

    Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). The authors conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress

  13. A Bayesian approach for estimating under-reported dengue incidence with a focus on non-linear associations between climate and dengue in Dhaka, Bangladesh.

    Science.gov (United States)

    Sharmin, Sifat; Glass, Kathryn; Viennet, Elvina; Harley, David

    2018-04-01

    Determining the relation between climate and dengue incidence is challenging due to under-reporting of disease and consequent biased incidence estimates. Non-linear associations between climate and incidence compound this. Here, we introduce a modelling framework to estimate dengue incidence from passive surveillance data while incorporating non-linear climate effects. We estimated the true number of cases per month using a Bayesian generalised linear model, developed in stages to adjust for under-reporting. A semi-parametric thin-plate spline approach was used to quantify non-linear climate effects. The approach was applied to data collected from the national dengue surveillance system of Bangladesh. The model estimated that only 2.8% (95% credible interval 2.7-2.8) of all cases in the capital Dhaka were reported through passive case reporting. The optimal mean monthly temperature for dengue transmission is 29℃ and average monthly rainfall above 15 mm decreases transmission. Our approach provides an estimate of true incidence and an understanding of the effects of temperature and rainfall on dengue transmission in Dhaka, Bangladesh.

  14. A Fuzzy Approach Using Generalized Dinkelbach’s Algorithm for Multiobjective Linear Fractional Transportation Problem

    Directory of Open Access Journals (Sweden)

    Nurdan Cetin

    2014-01-01

    Full Text Available We consider a multiobjective linear fractional transportation problem (MLFTP with several fractional criteria, such as, the maximization of the transport profitability like profit/cost or profit/time, and its two properties are source and destination. Our aim is to introduce MLFTP which has not been studied in literature before and to provide a fuzzy approach which obtain a compromise Pareto-optimal solution for this problem. To do this, first, we present a theorem which shows that MLFTP is always solvable. And then, reducing MLFTP to the Zimmermann’s “min” operator model which is the max-min problem, we construct Generalized Dinkelbach’s Algorithm for solving the obtained problem. Furthermore, we provide an illustrative numerical example to explain this fuzzy approach.

  15. The dynamics of p53 in single cells: physiologically based ODE and reaction–diffusion PDE models

    International Nuclear Information System (INIS)

    Eliaš, Ján; Clairambault, Jean; Dimitrio, Luna; Natalini, Roberto

    2014-01-01

    The intracellular signalling network of the p53 protein plays important roles in genome protection and the control of cell cycle phase transitions. Recently observed oscillatory behaviour in single cells under stress conditions has inspired several research groups to simulate and study the dynamics of the protein with the aim of gaining a proper understanding of the physiological meanings of the oscillations. We propose compartmental ODE and PDE models of p53 activation and regulation in single cells following DNA damage and we show that the p53 oscillations can be retrieved by plainly involving p53–Mdm2 and ATM–p53–Wip1 negative feedbacks, which are sufficient for oscillations experimentally, with no further need to introduce any delays into the protein responses and without considering additional positive feedback. (paper)

  16. Social inequality, lifestyles and health - a non-linear canonical correlation analysis based on the approach of Pierre Bourdieu.

    Science.gov (United States)

    Grosse Frie, Kirstin; Janssen, Christian

    2009-01-01

    Based on the theoretical and empirical approach of Pierre Bourdieu, a multivariate non-linear method is introduced as an alternative way to analyse the complex relationships between social determinants and health. The analysis is based on face-to-face interviews with 695 randomly selected respondents aged 30 to 59. Variables regarding socio-economic status, life circumstances, lifestyles, health-related behaviour and health were chosen for the analysis. In order to determine whether the respondents can be differentiated and described based on these variables, a non-linear canonical correlation analysis (OVERALS) was performed. The results can be described on three dimensions; Eigenvalues add up to the fit of 1.444, which can be interpreted as approximately 50 % of explained variance. The three-dimensional space illustrates correspondences between variables and provides a framework for interpretation based on latent dimensions, which can be described by age, education, income and gender. Using non-linear canonical correlation analysis, health characteristics can be analysed in conjunction with socio-economic conditions and lifestyles. Based on Bourdieus theoretical approach, the complex correlations between these variables can be more substantially interpreted and presented.

  17. The 1D Richards' equation in two layered soils: a Filippov approach to treat discontinuities

    Science.gov (United States)

    Berardi, Marco; Difonzo, Fabio; Vurro, Michele; Lopez, Luciano

    2018-05-01

    The infiltration process into the soil is generally modeled by the Richards' partial differential equation (PDE). In this paper a new approach for modeling the infiltration process through the interface of two different soils is proposed, where the interface is seen as a discontinuity surface defined by suitable state variables. Thus, the original 1D Richards' PDE, enriched by a particular choice of the boundary conditions, is first approximated by means of a time semidiscretization, that is by means of the transversal method of lines (TMOL). In such a way a sequence of discontinuous initial value problems, described by a sequence of second order differential systems in the space variable, is derived. Then, Filippov theory on discontinuous dynamical systems may be applied in order to study the relevant dynamics of the problem. The numerical integration of the semidiscretized differential system will be performed by using a one-step method, which employs an event driven procedure to locate the discontinuity surface and to adequately change the vector field.

  18. A linear programming approach to max-sum problem: a review.

    Science.gov (United States)

    Werner, Tomás

    2007-07-01

    The max-sum labeling problem, defined as maximizing a sum of binary (i.e., pairwise) functions of discrete variables, is a general NP-hard optimization problem with many applications, such as computing the MAP configuration of a Markov random field. We review a not widely known approach to the problem, developed by Ukrainian researchers Schlesinger et al. in 1976, and show how it contributes to recent results, most importantly, those on the convex combination of trees and tree-reweighted max-product. In particular, we review Schlesinger et al.'s upper bound on the max-sum criterion, its minimization by equivalent transformations, its relation to the constraint satisfaction problem, the fact that this minimization is dual to a linear programming relaxation of the original problem, and the three kinds of consistency necessary for optimality of the upper bound. We revisit problems with Boolean variables and supermodular problems. We describe two algorithms for decreasing the upper bound. We present an example application for structural image analysis.

  19. Bayes linear statistics, theory & methods

    CERN Document Server

    Goldstein, Michael

    2007-01-01

    Bayesian methods combine information available from data with any prior information available from expert knowledge. The Bayes linear approach follows this path, offering a quantitative structure for expressing beliefs, and systematic methods for adjusting these beliefs, given observational data. The methodology differs from the full Bayesian methodology in that it establishes simpler approaches to belief specification and analysis based around expectation judgements. Bayes Linear Statistics presents an authoritative account of this approach, explaining the foundations, theory, methodology, and practicalities of this important field. The text provides a thorough coverage of Bayes linear analysis, from the development of the basic language to the collection of algebraic results needed for efficient implementation, with detailed practical examples. The book covers:The importance of partial prior specifications for complex problems where it is difficult to supply a meaningful full prior probability specification...

  20. Penalized linear regression for discrete ill-posed problems: A hybrid least-squares and mean-squared error approach

    KAUST Repository

    Suliman, Mohamed Abdalla Elhag

    2016-12-19

    This paper proposes a new approach to find the regularization parameter for linear least-squares discrete ill-posed problems. In the proposed approach, an artificial perturbation matrix with a bounded norm is forced into the discrete ill-posed model matrix. This perturbation is introduced to enhance the singular-value (SV) structure of the matrix and hence to provide a better solution. The proposed approach is derived to select the regularization parameter in a way that minimizes the mean-squared error (MSE) of the estimator. Numerical results demonstrate that the proposed approach outperforms a set of benchmark methods in most cases when applied to different scenarios of discrete ill-posed problems. Jointly, the proposed approach enjoys the lowest run-time and offers the highest level of robustness amongst all the tested methods.

  1. A linear programming approach for estimating the structure of a sparse linear genetic network from transcript profiling data

    Directory of Open Access Journals (Sweden)

    Chandra Nagasuma R

    2009-02-01

    Full Text Available Abstract Background A genetic network can be represented as a directed graph in which a node corresponds to a gene and a directed edge specifies the direction of influence of one gene on another. The reconstruction of such networks from transcript profiling data remains an important yet challenging endeavor. A transcript profile specifies the abundances of many genes in a biological sample of interest. Prevailing strategies for learning the structure of a genetic network from high-dimensional transcript profiling data assume sparsity and linearity. Many methods consider relatively small directed graphs, inferring graphs with up to a few hundred nodes. This work examines large undirected graphs representations of genetic networks, graphs with many thousands of nodes where an undirected edge between two nodes does not indicate the direction of influence, and the problem of estimating the structure of such a sparse linear genetic network (SLGN from transcript profiling data. Results The structure learning task is cast as a sparse linear regression problem which is then posed as a LASSO (l1-constrained fitting problem and solved finally by formulating a Linear Program (LP. A bound on the Generalization Error of this approach is given in terms of the Leave-One-Out Error. The accuracy and utility of LP-SLGNs is assessed quantitatively and qualitatively using simulated and real data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM initiative provides gold standard data sets and evaluation metrics that enable and facilitate the comparison of algorithms for deducing the structure of networks. The structures of LP-SLGNs estimated from the INSILICO1, INSILICO2 and INSILICO3 simulated DREAM2 data sets are comparable to those proposed by the first and/or second ranked teams in the DREAM2 competition. The structures of LP-SLGNs estimated from two published Saccharomyces cerevisae cell cycle transcript profiling data sets capture known

  2. Linearized versus non-linear inverse methods for seismic localization of underground sources

    DEFF Research Database (Denmark)

    Oh, Geok Lian; Jacobsen, Finn

    2013-01-01

    The problem of localization of underground sources from seismic measurements detected by several geophones located on the ground surface is addressed. Two main approaches to the solution of the problem are considered: a beamforming approach that is derived from the linearized inversion problem, a...

  3. Experimental Approaches at Linear Colliders

    International Nuclear Information System (INIS)

    Jaros, John A

    2002-01-01

    Precision measurements have played a vital role in our understanding of elementary particle physics. Experiments performed using e + e - collisions have contributed an essential part. Recently, the precision measurements at LEP and SLC have probed the standard model at the quantum level and severely constrained the mass of the Higgs boson [1]. Coupled with the limits on the Higgs mass from direct searches [2], this enables the mass to be constrained to be in the range 115-205 GeV. Developments in accelerator R and D have matured to the point where one could contemplate construction of a linear collider with initial energy in the 500 GeV range and a credible upgrade path to ∼ 1 TeV. Now is therefore the correct time to critically evaluate the case for such a facility

  4. Comparison of Numerical Approaches to a Steady-State Landscape Equation

    Science.gov (United States)

    Bachman, S.; Peckham, S.

    2008-12-01

    A mathematical model of an idealized fluvial landscape has been developed, in which a land surface will evolve to preserve dendritic channel networks as the surface is lowered. The physical basis for this model stems from the equations for conservation of mass for water and sediment. These equations relate the divergence of the 2D vector fields showing the unit-width discharge of water and sediment to the excess rainrate and tectonic uplift on the land surface. The 2D flow direction is taken to be opposite to the water- surface gradient vector. These notions are combined with a generalized Manning-type flow resistance formula and a generalized sediment transport law to give a closed mathematical system that can, in principle, be solved for all variables of interest: discharge of water and sediment, land surface height, vertically- averaged flow velocity, water depth, and shear stress. The hydraulic geometry equations (Leopold et. al, 1964, 1995) are used to incorporate width, depth, velocity, and slope of river channels as powers of the mean-annual river discharge. Combined, they give the unit- width discharge of the stream as a power, γ, of the water surface slope. The simplified steady-state model takes into account three components among those listed above: conservation of mass for water, flow opposite the gradient, and a slope-discharge exponent γ = -1 to reflect mature drainage networks. The mathematical representation of this model appears as a second-order hyperbolic partial differential equation (PDE) where the diffusivity is inversely proportional to the square of the local surface slope. The highly nonlinear nature of this PDE has made it very difficult to solve both analytically and numerically. We present simplistic analytic solutions to this equation which are used to test the validity of the numerical algorithms. We also present three such numerical approaches which have been used in solving the differential equation. The first is based on a

  5. lpNet: a linear programming approach to reconstruct signal transduction networks.

    Science.gov (United States)

    Matos, Marta R A; Knapp, Bettina; Kaderali, Lars

    2015-10-01

    With the widespread availability of high-throughput experimental technologies it has become possible to study hundreds to thousands of cellular factors simultaneously, such as coding- or non-coding mRNA or protein concentrations. Still, extracting information about the underlying regulatory or signaling interactions from these data remains a difficult challenge. We present a flexible approach towards network inference based on linear programming. Our method reconstructs the interactions of factors from a combination of perturbation/non-perturbation and steady-state/time-series data. We show both on simulated and real data that our methods are able to reconstruct the underlying networks fast and efficiently, thus shedding new light on biological processes and, in particular, into disease's mechanisms of action. We have implemented the approach as an R package available through bioconductor. This R package is freely available under the Gnu Public License (GPL-3) from bioconductor.org (http://bioconductor.org/packages/release/bioc/html/lpNet.html) and is compatible with most operating systems (Windows, Linux, Mac OS) and hardware architectures. bettina.knapp@helmholtz-muenchen.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Linearizing feedforward/feedback attitude control

    Science.gov (United States)

    Paielli, Russell A.; Bach, Ralph E.

    1991-01-01

    An approach to attitude control theory is introduced in which a linear form is postulated for the closed-loop rotation error dynamics, then the exact control law required to realize it is derived. The nonminimal (four-component) quaternion form is used to attitude because it is globally nonsingular, but the minimal (three-component) quaternion form is used for attitude error because it has no nonlinear constraints to prevent the rotational error dynamics from being linearized, and the definition of the attitude error is based on quaternion algebra. This approach produces an attitude control law that linearizes the closed-loop rotational error dynamics exactly, without any attitude singularities, even if the control errors become large.

  7. Fuzzy linear programming approach for solving transportation

    Indian Academy of Sciences (India)

    Transportation problem (TP) is an important network structured linear programming problem that arises in several contexts and has deservedly received a great deal of attention in the literature. The central concept in this problem is to find the least total transportation cost of a commodity in order to satisfy demands at ...

  8. Linear combination of forecasts with numerical adjustment via MINIMAX non-linear programming

    Directory of Open Access Journals (Sweden)

    Jairo Marlon Corrêa

    2016-03-01

    Full Text Available This paper proposes a linear combination of forecasts obtained from three forecasting methods (namely, ARIMA, Exponential Smoothing and Artificial Neural Networks whose adaptive weights are determined via a multi-objective non-linear programming problem, which seeks to minimize, simultaneously, the statistics: MAE, MAPE and MSE. The results achieved by the proposed combination are compared with the traditional approach of linear combinations of forecasts, where the optimum adaptive weights are determined only by minimizing the MSE; with the combination method by arithmetic mean; and with individual methods

  9. A Hybrid Density Functional Theory/Molecular Mechanics Approach for Linear Response Properties in Heterogeneous Environments.

    Science.gov (United States)

    Rinkevicius, Zilvinas; Li, Xin; Sandberg, Jaime A R; Mikkelsen, Kurt V; Ågren, Hans

    2014-03-11

    We introduce a density functional theory/molecular mechanical approach for computation of linear response properties of molecules in heterogeneous environments, such as metal surfaces or nanoparticles embedded in solvents. The heterogeneous embedding environment, consisting from metallic and nonmetallic parts, is described by combined force fields, where conventional force fields are used for the nonmetallic part and capacitance-polarization-based force fields are used for the metallic part. The presented approach enables studies of properties and spectra of systems embedded in or placed at arbitrary shaped metallic surfaces, clusters, or nanoparticles. The capability and performance of the proposed approach is illustrated by sample calculations of optical absorption spectra of thymidine absorbed on gold surfaces in an aqueous environment, where we study how different organizations of the gold surface and how the combined, nonadditive effect of the two environments is reflected in the optical absorption spectrum.

  10. Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells.

    Science.gov (United States)

    Duranti, Guglielmo; Ceci, Roberta; Sgrò, Paolo; Sabatini, Stefania; Di Luigi, Luigi

    2017-05-01

    Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

  11. Controllability of partial differential equations governed by multiplicative controls

    CERN Document Server

    Khapalov, Alexander Y

    2010-01-01

    The goal of this monograph is to address the issue of the global controllability of partial differential equations in the context of multiplicative (or bilinear) controls, which enter the model equations as coefficients. The mathematical models we examine include the linear and nonlinear parabolic and hyperbolic PDE's, the Schrödinger equation, and coupled hybrid nonlinear distributed parameter systems modeling the swimming phenomenon. The book offers a new, high-quality and intrinsically nonlinear methodology to approach the aforementioned highly nonlinear controllability problems.

  12. Primordial black holes in linear and non-linear regimes

    Energy Technology Data Exchange (ETDEWEB)

    Allahyari, Alireza; Abolhasani, Ali Akbar [Department of Physics, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Firouzjaee, Javad T., E-mail: allahyari@physics.sharif.edu, E-mail: j.taghizadeh.f@ipm.ir [School of Astronomy, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2017-06-01

    We revisit the formation of primordial black holes (PBHs) in the radiation-dominated era for both linear and non-linear regimes, elaborating on the concept of an apparent horizon. Contrary to the expectation from vacuum models, we argue that in a cosmological setting a density fluctuation with a high density does not always collapse to a black hole. To this end, we first elaborate on the perturbation theory for spherically symmetric space times in the linear regime. Thereby, we introduce two gauges. This allows to introduce a well defined gauge-invariant quantity for the expansion of null geodesics. Using this quantity, we argue that PBHs do not form in the linear regime irrespective of the density of the background. Finally, we consider the formation of PBHs in non-linear regimes, adopting the spherical collapse picture. In this picture, over-densities are modeled by closed FRW models in the radiation-dominated era. The difference of our approach is that we start by finding an exact solution for a closed radiation-dominated universe. This yields exact results for turn-around time and radius. It is important that we take the initial conditions from the linear perturbation theory. Additionally, instead of using uniform Hubble gauge condition, both density and velocity perturbations are admitted in this approach. Thereby, the matching condition will impose an important constraint on the initial velocity perturbations δ {sup h} {sub 0} = −δ{sub 0}/2. This can be extended to higher orders. Using this constraint, we find that the apparent horizon of a PBH forms when δ > 3 at turn-around time. The corrections also appear from the third order. Moreover, a PBH forms when its apparent horizon is outside the sound horizon at the re-entry time. Applying this condition, we infer that the threshold value of the density perturbations at horizon re-entry should be larger than δ {sub th} > 0.7.

  13. Comparison of efficacy and satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction.

    Science.gov (United States)

    Megas, Georgios; Papadopoulos, Georgios; Stathouros, Georgios; Moschonas, Dimitrios; Gkialas, Ioannis; Ntoumas, Konstantinos

    2013-07-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Erectile dysfunction after nerve-sparing radical retropubic prostatectomy constitutes a challenge to the urologist. The mainstay of medical treatment after radical prostatectomy to restore spontaneous erectile function remains phosphodiesterase (PDE5) inhibitors, despite the fact that data from animal studies suggesting that PDE5 inhibitors can prevent smooth muscle apoptosis and fibrosis have not yet been extrapolated to humans because of a lack of standardized protocols. If the above treatment fails, second-line therapies such as intraurethral prostaglandins, penile injection therapy and vacuum devices are offered. When less invasive therapies are ineffective, interventions that preserve sexual function such as penile prosthesis implantation become the treatment of choice. Our study reveals the alternative of penile prosthesis implantation as first-line treatment in erectile dysfunction after nerve-sparing radical prostatectomy. It also highlights its superiority to the oral PDE5 inhibitor treatment, regarding the erection, frequency, firmness, maintenance and penetration ability. This suggests that a concept of an early penile intervention in the future would be promising for those patients who wish to remain sexually active without depending on oral formulations with doubtful and delayed results. To evaluate the outcome of penile prosthesis surgery in comparison to oral phosphodiesterase type 5 (PDE5) inhibitor administration, in men with erectile dysfunction after nerve-sparing radical prostatectomy, as early penile intervention therapy. A total of 174 patients treated by nerve-sparing retropubic radical prostatectomy (RRP) for clinically localized prostate cancer, between January 2006 and September 2009 enrolled in the study, 153 patients fulfilled the inclusion criteria, and 69 (45%) patients presented with post-RRP erectile dysfunction 6 months after primary surgery. Fifty-four patients were disease

  14. A hybrid approach to parameter identification of linear delay differential equations involving multiple delays

    Science.gov (United States)

    Marzban, Hamid Reza

    2018-05-01

    In this paper, we are concerned with the parameter identification of linear time-invariant systems containing multiple delays. The approach is based upon a hybrid of block-pulse functions and Legendre's polynomials. The convergence of the proposed procedure is established and an upper error bound with respect to the L2-norm associated with the hybrid functions is derived. The problem under consideration is first transformed into a system of algebraic equations. The least squares technique is then employed for identification of the desired parameters. Several multi-delay systems of varying complexity are investigated to evaluate the performance and capability of the proposed approximation method. It is shown that the proposed approach is also applicable to a class of nonlinear multi-delay systems. It is demonstrated that the suggested procedure provides accurate results for the desired parameters.

  15. Performance improvement of shunt active power filter based on non-linear least-square approach

    DEFF Research Database (Denmark)

    Terriche, Yacine

    2018-01-01

    Nowadays, the shunt active power filters (SAPFs) have become a popular solution for power quality issues. A crucial issue in controlling the SAPFs which is highly correlated with their accuracy, flexibility and dynamic behavior, is generating the reference compensating current (RCC). The synchron......Nowadays, the shunt active power filters (SAPFs) have become a popular solution for power quality issues. A crucial issue in controlling the SAPFs which is highly correlated with their accuracy, flexibility and dynamic behavior, is generating the reference compensating current (RCC......). The synchronous reference frame (SRF) approach is widely used for generating the RCC due to its simplicity and computation efficiency. However, the SRF approach needs precise information of the voltage phase which becomes a challenge under adverse grid conditions. A typical solution to answer this need....... This paper proposes an improved open loop strategy which is unconditionally stable and flexible. The proposed method which is based on non-linear least square (NLS) approach can extract the fundamental voltage and estimates its phase within only half cycle, even in the presence of odd harmonics and dc offset...

  16. Applied linear algebra and matrix analysis

    CERN Document Server

    Shores, Thomas S

    2018-01-01

    In its second edition, this textbook offers a fresh approach to matrix and linear algebra. Its blend of theory, computational exercises, and analytical writing projects is designed to highlight the interplay between these aspects of an application. This approach places special emphasis on linear algebra as an experimental science that provides tools for solving concrete problems. The second edition’s revised text discusses applications of linear algebra like graph theory and network modeling methods used in Google’s PageRank algorithm. Other new materials include modeling examples of diffusive processes, linear programming, image processing, digital signal processing, and Fourier analysis. These topics are woven into the core material of Gaussian elimination and other matrix operations; eigenvalues, eigenvectors, and discrete dynamical systems; and the geometrical aspects of vector spaces. Intended for a one-semester undergraduate course without a strict calculus prerequisite, Applied Linear Algebra and M...

  17. GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses.

    Science.gov (United States)

    Bruno, O; Fedele, E; Prickaerts, J; Parker, L A; Canepa, E; Brullo, C; Cavallero, A; Gardella, E; Balbi, A; Domenicotti, C; Bollen, E; Gijselaers, H J M; Vanmierlo, T; Erb, K; Limebeer, C L; Argellati, F; Marinari, U M; Pronzato, M A; Ricciarelli, R

    2011-12-01

    Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-β (Aβ) levels. To measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Aβ peptides were measured in hippocampal tissues and cultured N2a cells by elisa. GEBR-7b increased hippocampal cAMP, did not influence Aβ levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents. Our results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  18. A land use regression model for ambient ultrafine particles in Montreal, Canada: A comparison of linear regression and a machine learning approach.

    Science.gov (United States)

    Weichenthal, Scott; Ryswyk, Keith Van; Goldstein, Alon; Bagg, Scott; Shekkarizfard, Maryam; Hatzopoulou, Marianne

    2016-04-01

    Existing evidence suggests that ambient ultrafine particles (UFPs) (regression model for UFPs in Montreal, Canada using mobile monitoring data collected from 414 road segments during the summer and winter months between 2011 and 2012. Two different approaches were examined for model development including standard multivariable linear regression and a machine learning approach (kernel-based regularized least squares (KRLS)) that learns the functional form of covariate impacts on ambient UFP concentrations from the data. The final models included parameters for population density, ambient temperature and wind speed, land use parameters (park space and open space), length of local roads and rail, and estimated annual average NOx emissions from traffic. The final multivariable linear regression model explained 62% of the spatial variation in ambient UFP concentrations whereas the KRLS model explained 79% of the variance. The KRLS model performed slightly better than the linear regression model when evaluated using an external dataset (R(2)=0.58 vs. 0.55) or a cross-validation procedure (R(2)=0.67 vs. 0.60). In general, our findings suggest that the KRLS approach may offer modest improvements in predictive performance compared to standard multivariable linear regression models used to estimate spatial variations in ambient UFPs. However, differences in predictive performance were not statistically significant when evaluated using the cross-validation procedure. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  19. A mixed integer linear programming approach for optimal DER portfolio, sizing, and placement in multi-energy microgrids

    International Nuclear Information System (INIS)

    Mashayekh, Salman; Stadler, Michael; Cardoso, Gonçalo; Heleno, Miguel

    2017-01-01

    Highlights: • This paper presents a MILP model for optimal design of multi-energy microgrids. • Our microgrid design includes optimal technology portfolio, placement, and operation. • Our model includes microgrid electrical power flow and heat transfer equations. • The case study shows advantages of our model over aggregate single-node approaches. • The case study shows the accuracy of the integrated linearized power flow model. - Abstract: Optimal microgrid design is a challenging problem, especially for multi-energy microgrids with electricity, heating, and cooling loads as well as sources, and multiple energy carriers. To address this problem, this paper presents an optimization model formulated as a mixed-integer linear program, which determines the optimal technology portfolio, the optimal technology placement, and the associated optimal dispatch, in a microgrid with multiple energy types. The developed model uses a multi-node modeling approach (as opposed to an aggregate single-node approach) that includes electrical power flow and heat flow equations, and hence, offers the ability to perform optimal siting considering physical and operational constraints of electrical and heating/cooling networks. The new model is founded on the existing optimization model DER-CAM, a state-of-the-art decision support tool for microgrid planning and design. The results of a case study that compares single-node vs. multi-node optimal design for an example microgrid show the importance of multi-node modeling. It has been shown that single-node approaches are not only incapable of optimal DER placement, but may also result in sub-optimal DER portfolio, as well as underestimation of investment costs.

  20. Fuzzy multiple linear regression: A computational approach

    Science.gov (United States)

    Juang, C. H.; Huang, X. H.; Fleming, J. W.

    1992-01-01

    This paper presents a new computational approach for performing fuzzy regression. In contrast to Bardossy's approach, the new approach, while dealing with fuzzy variables, closely follows the conventional regression technique. In this approach, treatment of fuzzy input is more 'computational' than 'symbolic.' The following sections first outline the formulation of the new approach, then deal with the implementation and computational scheme, and this is followed by examples to illustrate the new procedure.

  1. Optimal control of coupled parabolic-hyperbolic non-autonomous PDEs: infinite-dimensional state-space approach

    Science.gov (United States)

    Aksikas, I.; Moghadam, A. Alizadeh; Forbes, J. F.

    2018-04-01

    This paper deals with the design of an optimal state-feedback linear-quadratic (LQ) controller for a system of coupled parabolic-hypebolic non-autonomous partial differential equations (PDEs). The infinite-dimensional state space representation and the corresponding operator Riccati differential equation are used to solve the control problem. Dynamical properties of the coupled system of interest are analysed to guarantee the existence and uniqueness of the solution of the LQ-optimal control problem and also to guarantee the exponential stability of the closed-loop system. Thanks to the eigenvalues and eigenfunctions of the parabolic operator and also the fact that the hyperbolic-associated operator Riccati differential equation can be converted to a scalar Riccati PDE, an algorithm to solve the LQ control problem has been presented. The results are applied to a non-isothermal packed-bed catalytic reactor. The LQ optimal controller designed in the early portion of the paper is implemented for the original non-linear model. Numerical simulations are performed to show the controller performances.

  2. Influence of linear-energy-dependent density of states on two-band superconductors: Three-square-well model approach

    International Nuclear Information System (INIS)

    Ogbuu, O.A.; Abah, O.C.; Asomba, G.C.; Okoye, C.M.I.

    2011-01-01

    We derived the transition temperature and the isotope exponent of two-band superconductor. We employed Bogoliubov-Valatin formalism assuming a three-square-well potential. The effect of linear-energy-dependent electronic DOS in superconductors is considered. The relevance of the studies to MgB 2 is analyzed. We have derived the expressions for the transition temperature and the isotope effect exponent within the framework of Bogoliubov-Valatin two-band formalism using a linear-energy-dependent electronic density of states assuming a three-square-well potentials model. Our results show that the approach could be used to account for a wide range of values of the transition temperature and isotope effect exponent. The relevance of the present calculations to MgB 2 is analyzed.

  3. Linear regression crash prediction models : issues and proposed solutions.

    Science.gov (United States)

    2010-05-01

    The paper develops a linear regression model approach that can be applied to : crash data to predict vehicle crashes. The proposed approach involves novice data aggregation : to satisfy linear regression assumptions; namely error structure normality ...

  4. Linear Unlearning for Cross-Validation

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Larsen, Jan

    1996-01-01

    The leave-one-out cross-validation scheme for generalization assessment of neural network models is computationally expensive due to replicated training sessions. In this paper we suggest linear unlearning of examples as an approach to approximative cross-validation. Further, we discuss...... time series prediction benchmark demonstrate the potential of the linear unlearning technique...

  5. Discovery of Boolean metabolic networks: integer linear programming based approach.

    Science.gov (United States)

    Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

    2018-04-11

    Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

  6. Enhancement of loss detection capability using a combination of the Kalman Filter/Linear Smoother and controllable unit accounting approach

    International Nuclear Information System (INIS)

    Pike, D.H.; Morrison, G.W.

    1979-01-01

    An approach to loss detection is presented which combines the optimal loss detection capability of state estimation techniques with a controllable unit accounting approach. The state estimation theory makes use of a linear system model which is capable of modeling the interaction of various controllable unit areas within a given facility. An example is presented which illustrates the increase in loss detection probability which is realizable with state estimation techniques. Comparisons are made with a Shewhart Control Chart and the CUSUM statistic

  7. Linear Algebra and Image Processing

    Science.gov (United States)

    Allali, Mohamed

    2010-01-01

    We use the computing technology digital image processing (DIP) to enhance the teaching of linear algebra so as to make the course more visual and interesting. Certainly, this visual approach by using technology to link linear algebra to DIP is interesting and unexpected to both students as well as many faculty. (Contains 2 tables and 11 figures.)

  8. Intelligent measurement and compensation of linear motor force ripple: a projection-based learning approach in the presence of noise

    Science.gov (United States)

    Liu, Yang; Song, Fazhi; Yang, Xiaofeng; Dong, Yue; Tan, Jiubin

    2018-06-01

    Due to their structural simplicity, linear motors are increasingly receiving attention for use in high velocity and high precision applications. The force ripple, as a space-periodic disturbance, however, would deteriorate the achievable dynamic performance. Conventional force ripple measurement approaches are time-consuming and have high requirements on the experimental conditions. In this paper, a novel learning identification algorithm is proposed for force ripple intelligent measurement and compensation. Existing identification schemes always use all the error signals to update the parameters in the force ripple. However, the error induced by noise is non-effective for force ripple identification, and even deteriorates the identification process. In this paper only the most pertinent information in the error signal is utilized for force ripple identification. Firstly, the effective error signals caused by the reference trajectory and the force ripple are extracted by projecting the overall error signals onto a subspace spanned by the physical model of the linear motor as well as the sinusoidal model of the force ripple. The time delay in the linear motor is compensated in the basis functions. Then, a data-driven approach is proposed to design the learning gain. It balances the trade-off between convergence speed and robustness against noise. Simulation and experimental results validate the proposed method and confirm its effectiveness and superiority.

  9. Estudo clínico fase I de carbonato de lodenafila, um novo tipo de inibidor de fosfodiesterase 5 (PDE5), em voluntários saudáveis do sexo masculino = : A phase I clinical trial of lodenafil carbonate, a new phosphodiesterase type 5 (PDE5) inhibitor, in healthy male volunteers

    OpenAIRE

    Hilton Oliveira dos Santos Filho

    2013-01-01

    Resumo: Carbonato de Lodenafila é um novo tipo de inibidor de fosfodiesterase 5 (PDE5) utilizado no tratamento da disfunção erétil. O presente estudo foi realizado para avaliar a segurança, tolerabilidade e farmacocinética do carbonato de lodenafila após a administração de doses orais únicas ascendentes (de 1 a 100 mg) a voluntários saudáveis do sexo masculino (n = 33). O estudo foi um estudo clínico fase I, aberto, de escalonamento de dose, utilizando a administração de doses orais únicas de...

  10. A Non-Linear Upscaling Approach for Wind Turbines Blades Based on Stresses

    NARCIS (Netherlands)

    Castillo Capponi, P.; Van Bussel, G.J.W.; Ashuri, T.; Kallesoe, B.

    2011-01-01

    The linear scaling laws for upscaling wind turbine blades show a linear increase of stresses due to the weight. However, the stresses should remain the same for a suitable design. Application of linear scaling laws may lead to an upscaled blade that may not be any more a feasible design. In this

  11. Non-local quasi-linear parabolic equations

    International Nuclear Information System (INIS)

    Amann, H

    2005-01-01

    This is a survey of the most common approaches to quasi-linear parabolic evolution equations, a discussion of their advantages and drawbacks, and a presentation of an entirely new approach based on maximal L p regularity. The general results here apply, above all, to parabolic initial-boundary value problems that are non-local in time. This is illustrated by indicating their relevance for quasi-linear parabolic equations with memory and, in particular, for time-regularized versions of the Perona-Malik equation of image processing

  12. Algorithms for non-linear M-estimation

    DEFF Research Database (Denmark)

    Madsen, Kaj; Edlund, O; Ekblom, H

    1997-01-01

    In non-linear regression, the least squares method is most often used. Since this estimator is highly sensitive to outliers in the data, alternatives have became increasingly popular during the last decades. We present algorithms for non-linear M-estimation. A trust region approach is used, where...

  13. Linear algebra done right

    CERN Document Server

    Axler, Sheldon

    2015-01-01

    This best-selling textbook for a second course in linear algebra is aimed at undergrad math majors and graduate students. The novel approach taken here banishes determinants to the end of the book. The text focuses on the central goal of linear algebra: understanding the structure of linear operators on finite-dimensional vector spaces. The author has taken unusual care to motivate concepts and to simplify proofs. A variety of interesting exercises in each chapter helps students understand and manipulate the objects of linear algebra. The third edition contains major improvements and revisions throughout the book. More than 300 new exercises have been added since the previous edition. Many new examples have been added to illustrate the key ideas of linear algebra. New topics covered in the book include product spaces, quotient spaces, and dual spaces. Beautiful new formatting creates pages with an unusually pleasant appearance in both print and electronic versions. No prerequisites are assumed other than the ...

  14. A LAGRANGIAN GAUSS-NEWTON-KRYLOV SOLVER FOR MASS- AND INTENSITY-PRESERVING DIFFEOMORPHIC IMAGE REGISTRATION.

    Science.gov (United States)

    Mang, Andreas; Ruthotto, Lars

    2017-01-01

    We present an efficient solver for diffeomorphic image registration problems in the framework of Large Deformations Diffeomorphic Metric Mappings (LDDMM). We use an optimal control formulation, in which the velocity field of a hyperbolic PDE needs to be found such that the distance between the final state of the system (the transformed/transported template image) and the observation (the reference image) is minimized. Our solver supports both stationary and non-stationary (i.e., transient or time-dependent) velocity fields. As transformation models, we consider both the transport equation (assuming intensities are preserved during the deformation) and the continuity equation (assuming mass-preservation). We consider the reduced form of the optimal control problem and solve the resulting unconstrained optimization problem using a discretize-then-optimize approach. A key contribution is the elimination of the PDE constraint using a Lagrangian hyperbolic PDE solver. Lagrangian methods rely on the concept of characteristic curves. We approximate these curves using a fourth-order Runge-Kutta method. We also present an efficient algorithm for computing the derivatives of the final state of the system with respect to the velocity field. This allows us to use fast Gauss-Newton based methods. We present quickly converging iterative linear solvers using spectral preconditioners that render the overall optimization efficient and scalable. Our method is embedded into the image registration framework FAIR and, thus, supports the most commonly used similarity measures and regularization functionals. We demonstrate the potential of our new approach using several synthetic and real world test problems with up to 14.7 million degrees of freedom.

  15. Partially Flipped Linear Algebra: A Team-Based Approach

    Science.gov (United States)

    Carney, Debra; Ormes, Nicholas; Swanson, Rebecca

    2015-01-01

    In this article we describe a partially flipped Introductory Linear Algebra course developed by three faculty members at two different universities. We give motivation for our partially flipped design and describe our implementation in detail. Two main features of our course design are team-developed preview videos and related in-class activities.…

  16. Two-Layer Linear MPC Approach Aimed at Walking Beam Billets Reheating Furnace Optimization

    Directory of Open Access Journals (Sweden)

    Silvia Maria Zanoli

    2017-01-01

    Full Text Available In this paper, the problem of the control and optimization of a walking beam billets reheating furnace located in an Italian steel plant is analyzed. An ad hoc Advanced Process Control framework has been developed, based on a two-layer linear Model Predictive Control architecture. This control block optimizes the steady and transient states of the considered process. Two main problems have been addressed. First, in order to manage all process conditions, a tailored module defines the process variables set to be included in the control problem. In particular, a unified approach for the selection on the control inputs to be used for control objectives related to the process outputs is guaranteed. The impact of the proposed method on the controller formulation is also detailed. Second, an innovative mathematical approach for stoichiometric ratios constraints handling has been proposed, together with their introduction in the controller optimization problems. The designed control system has been installed on a real plant, replacing operators’ mental model in the conduction of local PID controllers. After two years from the first startup, a strong energy efficiency improvement has been observed.

  17. Mamdani-Fuzzy Modeling Approach for Quality Prediction of Non-Linear Laser Lathing Process

    Science.gov (United States)

    Sivaraos; Khalim, A. Z.; Salleh, M. S.; Sivakumar, D.; Kadirgama, K.

    2018-03-01

    Lathing is a process to fashioning stock materials into desired cylindrical shapes which usually performed by traditional lathe machine. But, the recent rapid advancements in engineering materials and precision demand gives a great challenge to the traditional method. The main drawback of conventional lathe is its mechanical contact which brings to the undesirable tool wear, heat affected zone, finishing, and dimensional accuracy especially taper quality in machining of stock with high length to diameter ratio. Therefore, a novel approach has been devised to investigate in transforming a 2D flatbed CO2 laser cutting machine into 3D laser lathing capability as an alternative solution. Three significant design parameters were selected for this experiment, namely cutting speed, spinning speed, and depth of cut. Total of 24 experiments were performed with eight (8) sequential runs where they were then replicated three (3) times. The experimental results were then used to establish Mamdani - Fuzzy predictive model where it yields the accuracy of more than 95%. Thus, the proposed Mamdani - Fuzzy modelling approach is found very much suitable and practical for quality prediction of non-linear laser lathing process for cylindrical stocks of 10mm diameter.

  18. Preconditioning for Allen–Cahn variational inequalities with non-local constraints

    KAUST Repository

    Blank, Luise

    2012-06-01

    The solution of Allen-Cahn variational inequalities with mass constraints is of interest in many applications. This problem can be solved both in its scalar and vector-valued form as a PDE-constrained optimization problem by means of a primal-dual active set method. At the heart of this method lies the solution of linear systems in saddle point form. In this paper we propose the use of Krylov-subspace solvers and suitable preconditioners for the saddle point systems. Numerical results illustrate the competitiveness of this approach. © 2012 Elsevier Inc.

  19. Partitioning of late gestation energy expenditure in ewes using indirect calorimetry and a linear regression approach

    DEFF Research Database (Denmark)

    Kiani, Alishir; Chwalibog, André; Nielsen, Mette O

    2007-01-01

    Late gestation energy expenditure (EE(gest)) originates from energy expenditure (EE) of development of conceptus (EE(conceptus)) and EE of homeorhetic adaptation of metabolism (EE(homeorhetic)). Even though EE(gest) is relatively easy to quantify, its partitioning is problematic. In the present...... study metabolizable energy (ME) intake ranges for twin-bearing ewes were 220-440, 350- 700, 350-900 kJ per metabolic body weight (W0.75) at week seven, five, two pre-partum respectively. Indirect calorimetry and a linear regression approach were used to quantify EE(gest) and then partition to EE......(conceptus) and EE(homeorhetic). Energy expenditure of basal metabolism of the non-gravid tissues (EE(bmng)), derived from the intercept of the linear regression equation of retained energy [kJ/W0.75] and ME intake [kJ/W(0.75)], was 298 [kJ/ W0.75]. Values of the intercepts of the regression equations at week seven...

  20. Quantifying the astronomical contribution to Pleistocene climate change: A non-linear, statistical approach

    Science.gov (United States)

    Crucifix, Michel; Wilkinson, Richard; Carson, Jake; Preston, Simon; Alemeida, Carlos; Rougier, Jonathan

    2013-04-01

    The existence of an action of astronomical forcing on the Pleistocene climate is almost undisputed. However, quantifying this action is not straightforward. In particular, the phenomenon of deglaciation is generally interpreted as a manifestation of instability, which is typical of non-linear systems. As a consequence, explaining the Pleistocene climate record as the addition of an astronomical contribution and noise-as often done using harmonic analysis tools-is potentially deceptive. Rather, we advocate a methodology in which non-linear stochastic dynamical systems are calibrated on the Pleistocene climate record. The exercise, though, requires careful statistical reasoning and state-of-the-art techniques. In fact, the problem has been judged to be mathematically 'intractable and unsolved' and some pragmatism is justified. In order to illustrate the methodology we consider one dynamical system that potentially captures four dynamical features of the Pleistocene climate : the existence of a saddle-node bifurcation in at least one of its slow components, a time-scale separation between a slow and a fast component, the action of astronomical forcing, and the existence a stochastic contribution to the system dynamics. This model is obviously not the only possible representation of Pleistocene dynamics, but it encapsulates well enough both our theoretical and empirical knowledge into a very simple form to constitute a valid starting point. The purpose of this poster is to outline the practical challenges in calibrating such a model on paleoclimate observations. Just as in time series analysis, there is no one single and universal test or criteria that would demonstrate the validity of an approach. Several methods exist to calibrate the model and judgement develops by the confrontation of the results of the different methods. In particular, we consider here the Kalman filter variants, the Particle Monte-Carlo Markov Chain, and two other variants of Sequential Monte

  1. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    Science.gov (United States)

    Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

  2. A Mixed-Integer Linear Programming approach to wind farm layout and inter-array cable routing

    DEFF Research Database (Denmark)

    Fischetti, Martina; Leth, John-Josef; Borchersen, Anders Bech

    2015-01-01

    A Mixed-Integer Linear Programming (MILP) approach is proposed to optimize the turbine allocation and inter-array offshore cable routing. The two problems are considered with a two steps strategy, solving the layout problem first and then the cable problem. We give an introduction to both problems...... and present the MILP models we developed to solve them. To deal with interference in the onshore cases, we propose an adaptation of the standard Jensen’s model, suitable for 3D cases. A simple Stochastic Programming variant of our model allows us to consider different wind scenarios in the optimization...

  3. A solution approach for non-linear analysis of concrete members

    International Nuclear Information System (INIS)

    Hadi, N. M.; Das, S.

    1999-01-01

    Non-linear solution of reinforced concrete structural members, at and beyond its maximum strength poses complex numerical problems. This is due to the fact that concrete exhibits strain softening behaviour once it reaches its maximum strength. This paper introduces an improved non-linear solution capable to overcome the numerical problems efficiently. The paper also presents a new concept of modeling discrete cracks in concrete members by using gap elements. Gap elements are placed in between two adjacent concrete elements in tensile zone. The magnitude of elongation of gap elements, which represents the width of the crack in concrete, increases edith the increase of tensile stress in those elements. As a result, transfer of local from one concrete element to adjacent elements reduces. Results of non-linear finite element analysis of three concrete beams using this new solution strategy are compared with those obtained by other researchers, and a good agreement is achieved. (authors). 13 refs. 9 figs.,

  4. Quantum dynamics of a vibronically coupled linear chain using a surrogate Hamiltonian approach

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myeong H., E-mail: myeong.lee@warwick.ac.uk; Troisi, Alessandro [Department of Chemistry and Centre for Scientific Computing, University of Warwick, Coventry CV4 7AL (United Kingdom)

    2016-06-07

    Vibronic coupling between the electronic and vibrational degrees of freedom has been reported to play an important role in charge and exciton transport in organic photovoltaic materials, molecular aggregates, and light-harvesting complexes. Explicitly accounting for effective vibrational modes rather than treating them as a thermal environment has been shown to be crucial to describe the effect of vibronic coupling. We present a methodology to study dissipative quantum dynamics of vibronically coupled systems based on a surrogate Hamiltonian approach, which is in principle not limited by Markov approximation or weak system-bath interaction, using a vibronic basis. We apply vibronic surrogate Hamiltonian method to a linear chain system and discuss how different types of relaxation process, intramolecular vibrational relaxation and intermolecular vibronic relaxation, influence population dynamics of dissipative vibronic systems.

  5. Approach for Self-Calibrating CO₂ Measurements with Linear Membrane-Based Gas Sensors.

    Science.gov (United States)

    Lazik, Detlef; Sood, Pramit

    2016-11-17

    Linear membrane-based gas sensors that can be advantageously applied for the measurement of a single gas component in large heterogeneous systems, e.g., for representative determination of CO₂ in the subsurface, can be designed depending on the properties of the observation object. A resulting disadvantage is that the permeation-based sensor response depends on operating conditions, the individual site-adapted sensor geometry, the membrane material, and the target gas component. Therefore, calibration is needed, especially of the slope, which could change over several orders of magnitude. A calibration-free approach based on an internal gas standard is developed to overcome the multi-criterial slope dependency. This results in a normalization of sensor response and enables the sensor to assess the significance of measurement. The approach was proofed on the example of CO₂ analysis in dry air with tubular PDMS membranes for various CO₂ concentrations of an internal standard. Negligible temperature dependency was found within an 18 K range. The transformation behavior of the measurement signal and the influence of concentration variations of the internal standard on the measurement signal were shown. Offsets that were adjusted based on the stated theory for the given measurement conditions and material data from the literature were in agreement with the experimentally determined offsets. A measurement comparison with an NDIR reference sensor shows an unexpectedly low bias (sensor response, and comparable statistical uncertainty.

  6. Macroscopic QED in linearly responding media and a Lorentz-Force approach to dispersion forces

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, Christian

    2008-07-08

    In this thesis, a very general quantization scheme for the macroscopic electromagnetic field in arbitrary linearly responding media is presented. It offers a unified approach to QED in such media. Applying the quantization scheme, a theory of the dispersion forces on the basis of the Lorentz force is developed. By regarding the dispersion force as the (ground-state or thermal-state) expectation value of the Lorentz force that acts on appropriately defined charge and current densities, Casimir, Casimir-Polder, and van der Waals forces are united in a very natural way that makes transparent their common physical basis. Application of the theory to planar structures yields generalizations of well-known Lifschitz and Casimir-type formulas. (orig.)

  7. Macroscopic QED in linearly responding media and a Lorentz-Force approach to dispersion forces

    International Nuclear Information System (INIS)

    Raabe, Christian

    2008-01-01

    In this thesis, a very general quantization scheme for the macroscopic electromagnetic field in arbitrary linearly responding media is presented. It offers a unified approach to QED in such media. Applying the quantization scheme, a theory of the dispersion forces on the basis of the Lorentz force is developed. By regarding the dispersion force as the (ground-state or thermal-state) expectation value of the Lorentz force that acts on appropriately defined charge and current densities, Casimir, Casimir-Polder, and van der Waals forces are united in a very natural way that makes transparent their common physical basis. Application of the theory to planar structures yields generalizations of well-known Lifschitz and Casimir-type formulas. (orig.)

  8. Polarizable Density Embedding

    DEFF Research Database (Denmark)

    Reinholdt, Peter; Kongsted, Jacob; Olsen, Jógvan Magnus Haugaard

    2017-01-01

    We analyze the performance of the polarizable density embedding (PDE) model-a new multiscale computational approach designed for prediction and rationalization of general molecular properties of large and complex systems. We showcase how the PDE model very effectively handles the use of large...

  9. Weighted graph based ordering techniques for preconditioned conjugate gradient methods

    Science.gov (United States)

    Clift, Simon S.; Tang, Wei-Pai

    1994-01-01

    We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

  10. A Facile Approach to Preparing Molecularly Imprinted Chitosan for Detecting 2,4,6-Tribromophenol with a Widely Linear Range

    Directory of Open Access Journals (Sweden)

    Limei Huang

    2017-04-01

    Full Text Available The environmental pollution of 2,4,6-tribromophenol (TBP has attracted attention. Based on an urgent need for the better provision of clean water, in situ determination of TBP is of great importance. Here, a facile and effective approach for detecting TBP is developed, based on coupling molecular imprinting technique with electrodeposition of chitosan (CS on the gold electrode. The TBP imprinting CS film was fabricated by using CS as functional material and TBP as template molecule. The experiments show that the morphologies and electrochemical properties of the imprinted film sensor was different from non-imprinted film electrode. The current of the imprinted film was linearly proportional to the TBP concentration, with a wide linear range of 1.0 × 10−7 mol•L−1 to 1.0 × 10−3 mol•L−1. By selecting drop-coating method as a reference for controlled trials with the same functional material, the results illustrated that the electrodeposition enjoyed a widely linear range advantage.

  11. Optimal Decision-Making in Fuzzy Economic Order Quantity (EOQ Model under Restricted Space: A Non-Linear Programming Approach

    Directory of Open Access Journals (Sweden)

    M. Pattnaik

    2013-08-01

    Full Text Available In this paper the concept of fuzzy Non-Linear Programming Technique is applied to solve an economic order quantity (EOQ model under restricted space. Since various types of uncertainties and imprecision are inherent in real inventory problems they are classically modeled using the approaches from the probability theory. However, there are uncertainties that cannot be appropriately treated by usual probabilistic models. The questions how to define inventory optimization tasks in such environment how to interpret optimal solutions arise. This paper allows the modification of the Single item EOQ model in presence of fuzzy decision making process where demand is related to the unit price and the setup cost varies with the quantity produced/Purchased. This paper considers the modification of objective function and storage area in the presence of imprecisely estimated parameters. The model is developed for the problem by employing different modeling approaches over an infinite planning horizon. It incorporates all concepts of a fuzzy arithmetic approach, the quantity ordered and the demand per unit compares both fuzzy non linear and other models. Investigation of the properties of an optimal solution allows developing an algorithm whose validity is illustrated through an example problem and ugh MATLAB (R2009a version software, the two and three dimensional diagrams are represented to the application. Sensitivity analysis of the optimal solution is also studied with respect to changes in different parameter values and to draw managerial insights of the decision problem.

  12. Accelerated Optimization in the PDE Framework: Formulations for the Active Contour Case

    KAUST Repository

    Yezzi, Anthony; Sundaramoorthi, Ganesh

    2017-01-01

    Following the seminal work of Nesterov, accelerated optimization methods have been used to powerfully boost the performance of first-order, gradient-based parameter estimation in scenarios where second-order optimization strategies are either inapplicable or impractical. Not only does accelerated gradient descent converge considerably faster than traditional gradient descent, but it also performs a more robust local search of the parameter space by initially overshooting and then oscillating back as it settles into a final configuration, thereby selecting only local minimizers with a basis of attraction large enough to contain the initial overshoot. This behavior has made accelerated and stochastic gradient search methods particularly popular within the machine learning community. In their recent PNAS 2016 paper, Wibisono, Wilson, and Jordan demonstrate how a broad class of accelerated schemes can be cast in a variational framework formulated around the Bregman divergence, leading to continuum limit ODE's. We show how their formulation may be further extended to infinite dimension manifolds (starting here with the geometric space of curves and surfaces) by substituting the Bregman divergence with inner products on the tangent space and explicitly introducing a distributed mass model which evolves in conjunction with the object of interest during the optimization process. The co-evolving mass model, which is introduced purely for the sake of endowing the optimization with helpful dynamics, also links the resulting class of accelerated PDE based optimization schemes to fluid dynamical formulations of optimal mass transport.

  13. Accelerated Optimization in the PDE Framework: Formulations for the Active Contour Case

    KAUST Repository

    Yezzi, Anthony

    2017-11-27

    Following the seminal work of Nesterov, accelerated optimization methods have been used to powerfully boost the performance of first-order, gradient-based parameter estimation in scenarios where second-order optimization strategies are either inapplicable or impractical. Not only does accelerated gradient descent converge considerably faster than traditional gradient descent, but it also performs a more robust local search of the parameter space by initially overshooting and then oscillating back as it settles into a final configuration, thereby selecting only local minimizers with a basis of attraction large enough to contain the initial overshoot. This behavior has made accelerated and stochastic gradient search methods particularly popular within the machine learning community. In their recent PNAS 2016 paper, Wibisono, Wilson, and Jordan demonstrate how a broad class of accelerated schemes can be cast in a variational framework formulated around the Bregman divergence, leading to continuum limit ODE\\'s. We show how their formulation may be further extended to infinite dimension manifolds (starting here with the geometric space of curves and surfaces) by substituting the Bregman divergence with inner products on the tangent space and explicitly introducing a distributed mass model which evolves in conjunction with the object of interest during the optimization process. The co-evolving mass model, which is introduced purely for the sake of endowing the optimization with helpful dynamics, also links the resulting class of accelerated PDE based optimization schemes to fluid dynamical formulations of optimal mass transport.

  14. New approach to solve fully fuzzy system of linear equations using ...

    Indian Academy of Sciences (India)

    This paper proposes two new methods to solve fully fuzzy system of linear equations. The fuzzy system has been converted to a crisp system of linear equations by using single and double parametric form of fuzzy numbers to obtain the non-negative solution. Double parametric form of fuzzy numbers is defined and applied ...

  15. A novel approach for epipolar resampling of cross-track linear pushbroom imagery using orbital parameters model

    Science.gov (United States)

    Jannati, Mojtaba; Valadan Zoej, Mohammad Javad; Mokhtarzade, Mehdi

    2018-03-01

    This paper presents a novel approach to epipolar resampling of cross-track linear pushbroom imagery using orbital parameters model (OPM). The backbone of the proposed method relies on modification of attitude parameters of linear array stereo imagery in such a way to parallelize the approximate conjugate epipolar lines (ACELs) with the instantaneous base line (IBL) of the conjugate image points (CIPs). Afterward, a complementary rotation is applied in order to parallelize all the ACELs throughout the stereo imagery. The new estimated attitude parameters are evaluated based on the direction of the IBL and the ACELs. Due to the spatial and temporal variability of the IBL (respectively changes in column and row numbers of the CIPs) and nonparallel nature of the epipolar lines in the stereo linear images, some polynomials in the both column and row numbers of the CIPs are used to model new attitude parameters. As the instantaneous position of sensors remains fix, the digital elevation model (DEM) of the area of interest is not required in the resampling process. According to the experimental results obtained from two pairs of SPOT and RapidEye stereo imagery with a high elevation relief, the average absolute values of remained vertical parallaxes of CIPs in the normalized images were obtained 0.19 and 0.28 pixels respectively, which confirm the high accuracy and applicability of the proposed method.

  16. Time-History Seismic Analysis of Masonry Buildings: A Comparison between Two Non-Linear Modelling Approaches

    Directory of Open Access Journals (Sweden)

    Michele Betti

    2015-05-01

    Full Text Available The paper presents a comparison between two numerical modelling approaches employed to investigate the seismic behavior of unreinforced masonry buildings with flexible diaphragms. The comparison is performed analyzing a two-story prototype tested on a shaking table at the CNR-ENEA research center of Casaccia (Italy. The first numerical model was built by using the finite element (FE technique, while the second one was built by a simplified macro-element (ME approach. Both models were employed to perform non-linear dynamic analyses, integrating the equations of motion by step-by-step procedures. The shaking table tests were simulated to analyze the behavior of the prototype from the initial elastic state until the development of extensive damage. The main results of the analyses are discussed and critically compared in terms of engineering parameters, such as accelerations, displacements and base shears. The effectiveness of both models within the investigated typology of buildings is then evaluated in depth.

  17. Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

    Science.gov (United States)

    Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

    2018-01-01

    Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

  18. A displacement-based approach for determining non-linear effects on pre-tensioned-cable cross-braced structures

    Science.gov (United States)

    Giaccu, Gian Felice; Caracoglia, Luca

    2017-04-01

    Pre-tensioned-cable bracing systems are widely employed in structural engineering to limit lateral deflections and stabilize structures. A suitable configuration of the pre-tensioned-cable bracing systems in a structure is an important issue since the internal force distribution, emerging from the interaction with the existing structure, significantly affects the structural dynamic behavior. The design, however, is often based on the intuition and the previous experience of the engineer. In recent years, the authors have been investigating the non-linear dynamic response of cable systems, installed on cable-stayed bridges, and in particular the so-called "cable-cross-tie systems" forming a cable network. The bracing cables (cross-ties) can exhibit slackening or snapping. Therefore, a non-linear unilateral model, combined with the taut-cable theory, is required to simulate the incipient slackening conditions in the stays. Capitalizing from this work on non-linear cable dynamics, this paper proposes a new approach to analyze, in laterally- braced truss structures, the unilateral effects and dynamic response accounting for the loss in the pre-tensioning force imparted to the bracing cables. This effect leads to non-linear vibration of the structure. In this preliminary study, the free vibrations of the structure are investigated by using the "Equivalent Linearization Method". A performance coefficient, a real positive number between 0.5 and 1.0, is defined and employed to monitor the relative reduction in the apparent stiffness of the braces during structural vibration, "mode by mode". It is shown that the system can exhibit alternate unilateral behavior of the cross-braces. A reduction of the performance coefficient close to fifty percent is observed in the braces when the initial pre-tensioning force is small. On the other hand the performance coefficient tends to one in the case of a high level of pre-stress. It is concluded that the performance coefficient may

  19. Multiaxial probabilistic elastic-plastic constitutive simulations of soils

    Science.gov (United States)

    Sadrinezhad, Arezoo

    Fokker-Planck-Kolmogorov (FPK) equation approach has recently been developed to simulate elastic-plastic constitutive behaviors of materials with uncertain material properties. The FPK equation approach transforms the stochastic constitutive rate equation, which is a stochastic, nonlinear, ordinary differential equation (ODE) in the stress-pseudo time space into a second-order accurate, deterministic, linear FPK partial differential equation (PDE) in the probability density of stress-pseudo time space. This approach does not suffer from the drawbacks of the traditional approaches such as the Monte Carlo approach and the perturbation approach for solving nonlinear ODEs with random coefficients. In this study, the existing one dimensional FPK framework for probabilistic constitutive modeling of soils is extended to multi--dimension. However, the multivariate FPK PDEs cannot be solved using the traditional mathematical techniques such as finite difference techniques due to their high computational cost. Therefore, computationally efficient algorithms based on the Fourier spectral approach are developed for solving a class of FPK PDEs that arises in probabilistic elasto-plasticity. This class includes linear FPK PDEs in (stress) space and (pseudo) time - having space-independent but time-dependent, and both space- and time-dependent coefficients - with impulse initial conditions and reflecting boundary conditions. The solution algorithms, rely on first mapping the stress space of the governing PDE between 0 and 2pi using the change of coordinates rule, followed by approximating the solution of the PDE in the 2pi-periodic domain by a finite Fourier series in the stress space and unknown time-dependent solution coefficients. Finally, the time-dependent solution coefficients are obtained from the initial condition. The accuracy and efficiency of the developed algorithms are tested. The developed algorithms are used to simulate uniaxial and multiaxial, monotonic and cyclic

  20. Strategies and approaches in plasmidome studies—uncovering plasmid diversity disregarding of linear elements?

    Science.gov (United States)

    Dib, Julián R.; Wagenknecht, Martin; Farías, María E.; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which—despite their frequent occurrence in a large number of bacteria—are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  1. Two-dimensional differential transform method for solving linear and non-linear Schroedinger equations

    International Nuclear Information System (INIS)

    Ravi Kanth, A.S.V.; Aruna, K.

    2009-01-01

    In this paper, we propose a reliable algorithm to develop exact and approximate solutions for the linear and nonlinear Schroedinger equations. The approach rest mainly on two-dimensional differential transform method which is one of the approximate methods. The method can easily be applied to many linear and nonlinear problems and is capable of reducing the size of computational work. Exact solutions can also be achieved by the known forms of the series solutions. Several illustrative examples are given to demonstrate the effectiveness of the present method.

  2. Linear determining equations for differential constraints

    International Nuclear Information System (INIS)

    Kaptsov, O V

    1998-01-01

    A construction of differential constraints compatible with partial differential equations is considered. Certain linear determining equations with parameters are used to find such differential constraints. They generalize the classical determining equations used in the search for admissible Lie operators. As applications of this approach equations of an ideal incompressible fluid and non-linear heat equations are discussed

  3. Re-examining the risk–return relationship in Europe: Linear or non-linear trade-off?

    OpenAIRE

    Salvador, Enrique; Floros, Christos; Arago, Vicent

    2014-01-01

    This paper analyzes the risk–return trade-off in Europe using recent data from 11 European stock markets. After relaxing the linear assumptions in the risk–return relationship by introducing a new approach that considers the current state of the market, we obtain significant evidence for a positive risk–return trade-off for low volatility states. However, this finding is reduced or even non-significant during periods of high volatility. Maintaining the linear assumption over the risk–return t...

  4. Code Samples Used for Complexity and Control

    Science.gov (United States)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    The following sections are included: * MathematicaⓇ Code * Generic Chaotic Simulator * Vector Differential Operators * NLS Explorer * 2C++ Code * C++ Lambda Functions for Real Calculus * Accelerometer Data Processor * Simple Predictor-Corrector Integrator * Solving the BVP with the Shooting Method * Linear Hyperbolic PDE Solver * Linear Elliptic PDE Solver * Method of Lines for a Set of the NLS Equations * C# Code * Iterative Equation Solver * Simulated Annealing: A Function Minimum * Simple Nonlinear Dynamics * Nonlinear Pendulum Simulator * Lagrangian Dynamics Simulator * Complex-Valued Crowd Attractor Dynamics * Freeform Fortran Code * Lorenz Attractor Simulator * Complex Lorenz Attractor * Simple SGE Soliton * Complex Signal Presentation * Gaussian Wave Packet * Hermitian Matrices * Euclidean L2-Norm * Vector/Matrix Operations * Plain C-Code: Levenberg-Marquardt Optimizer * Free Basic Code: 2D Crowd Dynamics with 3000 Agents

  5. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) determination of stimulants, anorectic drugs and phosphodiesterase 5 inhibitors (PDE5I) in food supplements.

    Science.gov (United States)

    Strano-Rossi, Sabina; Odoardi, Sara; Castrignanò, Erika; Serpelloni, Giovanni; Chiarotti, Marcello

    2015-03-15

    The paper describes a liquid chromatography/high resolution mass spectrometry LC/HRMS method for the simultaneous identification and quantification of stimulants (ephedrines, caffeine, anorectic drugs such as phentermine, phendimetrazine, phenmetrazine, fenfluramine, benfluorex, mephentermine, fencanfamine, sibutramine) and PDE5I (sildenafil, vardenafil and tadalafil) in food supplements using a benchtop Orbitrap mass spectrometer. The mass detector, with a nominal resolving power of 100,000 (FWHM at m/z 200), operated in full scan mode in ESI positive ionization mode. Analytes were identified by retention times, accurate masses and correspondence of experimental and calculated isotopic patterns. The limits of detection (LOD) obtained varied from 1 to 25 ng g(-1) and limits of quantification (LOQ) were 50 ng g(-1) for all compounds. The method was linear for all the analytes in the ranges from 50 to 2000 ng g(-1), giving correlation coefficients>0.99. Accuracy (intended as %E) and repeatability (% CV) were always lower than 15%. The method was applied to the analysis of 36 dietary supplements, revealing the presence of ephedrine and/or pseudoephedrine in four of them, caffeine in eight of them and sildenafil in four of them. In one case, ephedrine was not reported on the label of the dietary supplement, as well as for caffeine in other two cases. A further confirmation of the analytes identity in positive samples was obtained through in-source fragmentation and comparison of the obtained fragments and their relative abundances with those from certified standards. As the acquisition mode is full scan, it would be also possible to re-process a previously acquired datafile for the investigation of untargeted analytes. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Linearly Adjustable International Portfolios

    International Nuclear Information System (INIS)

    Fonseca, R. J.; Kuhn, D.; Rustem, B.

    2010-01-01

    We present an approach to multi-stage international portfolio optimization based on the imposition of a linear structure on the recourse decisions. Multiperiod decision problems are traditionally formulated as stochastic programs. Scenario tree based solutions however can become intractable as the number of stages increases. By restricting the space of decision policies to linear rules, we obtain a conservative tractable approximation to the original problem. Local asset prices and foreign exchange rates are modelled separately, which allows for a direct measure of their impact on the final portfolio value.

  7. Linearly Adjustable International Portfolios

    Science.gov (United States)

    Fonseca, R. J.; Kuhn, D.; Rustem, B.

    2010-09-01

    We present an approach to multi-stage international portfolio optimization based on the imposition of a linear structure on the recourse decisions. Multiperiod decision problems are traditionally formulated as stochastic programs. Scenario tree based solutions however can become intractable as the number of stages increases. By restricting the space of decision policies to linear rules, we obtain a conservative tractable approximation to the original problem. Local asset prices and foreign exchange rates are modelled separately, which allows for a direct measure of their impact on the final portfolio value.

  8. Need for Linear Revitalization - Gdynia Case

    Science.gov (United States)

    Sas-Bojarska, Aleksandra

    2017-10-01

    The aim of the article is to discuss the need of defining and implementation of the linear revitalization - the new approach related to the revitalization processes. The results of the preliminary investigations indicate that this kind of revitalization seems to be an important tool supporting city management and planning, especially in cases of cities fragmentation - causing lack of physical, social, economic and ecological cohesion. The problems which may occur in such situations could be, in author’s opinion, solved with the use of linear revitalization. Linear revitalization relates to various linear city structures, which need a renewal. The article presents the idea of new attitude, character of specific actions related to degraded linear structures, draft classification, as well as the potential benefits to the city structure which could be reached due to the linear revitalization implementation. The theoretical deliberations are supplemented by the description and assessment of the chosen case study from Gdynia in Poland. The Kwiatkowskiego Route in Gdynia, playing important role in the city traffic as the external connection, creates the barrier in the city structure, causing many negative effects. Author presents specific problems related to chosen example, and the ways to solve them and to connect city structure. The main conclusion of the study is that the presented approach may be, in author’s opinion, the beginning of the discussion related to the linear revitalization, which may become an important and effective tool of sustainable city development. It may help overcoming physical barriers, and minimise functional, economic, social, mental and environmental conflicts caused by city fragmentation.

  9. Polarized Electrons for Linear Colliders

    International Nuclear Information System (INIS)

    Clendenin, J.

    2004-01-01

    Future electron-positron linear colliders require a highly polarized electron beam with a pulse structure that depends primarily on whether the acceleration utilizes warm or superconducting rf structures. The International Linear Collider (ILC) will use cold structures for the main linac. It is shown that a dc-biased polarized photoelectron source such as successfully used for the SLC can meet the charge requirements for the ILC micropulse with a polarization approaching 90%

  10. Chiropractic biophysics technique: a linear algebra approach to posture in chiropractic.

    Science.gov (United States)

    Harrison, D D; Janik, T J; Harrison, G R; Troyanovich, S; Harrison, D E; Harrison, S O

    1996-10-01

    This paper discusses linear algebra as applied to human posture in chiropractic, specifically chiropractic biophysics technique (CBP). Rotations, reflections and translations are geometric functions studied in vector spaces in linear algebra. These mathematical functions are termed rigid body transformations and are applied to segmental spinal movement in the literature. Review of the literature indicates that these linear algebra concepts have been used to describe vertebral motion. However, these rigid body movers are presented here as applying to the global postural movements of the head, thoracic cage and pelvis. The unique inverse functions of rotations, reflections and translations provide a theoretical basis for making postural corrections in neutral static resting posture. Chiropractic biophysics technique (CBP) uses these concepts in examination procedures, manual spinal manipulation, instrument assisted spinal manipulation, postural exercises, extension traction and clinical outcome measures.

  11. Noise and non-linearities in high-throughput data

    International Nuclear Information System (INIS)

    Nguyen, Viet-Anh; Lió, Pietro; Koukolíková-Nicola, Zdena; Bagnoli, Franco

    2009-01-01

    High-throughput data analyses are becoming common in biology, communications, economics and sociology. The vast amounts of data are usually represented in the form of matrices and can be considered as knowledge networks. Spectra-based approaches have proved useful in extracting hidden information within such networks and for estimating missing data, but these methods are based essentially on linear assumptions. The physical models of matching, when applicable, often suggest non-linear mechanisms, that may sometimes be identified as noise. The use of non-linear models in data analysis, however, may require the introduction of many parameters, which lowers the statistical weight of the model. According to the quality of data, a simpler linear analysis may be more convenient than more complex approaches. In this paper, we show how a simple non-parametric Bayesian model may be used to explore the role of non-linearities and noise in synthetic and experimental data sets

  12. Advanced statistics: linear regression, part II: multiple linear regression.

    Science.gov (United States)

    Marill, Keith A

    2004-01-01

    The applications of simple linear regression in medical research are limited, because in most situations, there are multiple relevant predictor variables. Univariate statistical techniques such as simple linear regression use a single predictor variable, and they often may be mathematically correct but clinically misleading. Multiple linear regression is a mathematical technique used to model the relationship between multiple independent predictor variables and a single dependent outcome variable. It is used in medical research to model observational data, as well as in diagnostic and therapeutic studies in which the outcome is dependent on more than one factor. Although the technique generally is limited to data that can be expressed with a linear function, it benefits from a well-developed mathematical framework that yields unique solutions and exact confidence intervals for regression coefficients. Building on Part I of this series, this article acquaints the reader with some of the important concepts in multiple regression analysis. These include multicollinearity, interaction effects, and an expansion of the discussion of inference testing, leverage, and variable transformations to multivariate models. Examples from the first article in this series are expanded on using a primarily graphic, rather than mathematical, approach. The importance of the relationships among the predictor variables and the dependence of the multivariate model coefficients on the choice of these variables are stressed. Finally, concepts in regression model building are discussed.

  13. On the dynamic analysis of piecewise-linear networks

    OpenAIRE

    Heemels, W.P.M.H.; Camlibel, M.K.; Schumacher, J.M.

    2002-01-01

    Piecewise-linear (PL) modeling is often used to approximate the behavior of nonlinear circuits. One of the possible PL modeling methodologies is based on the linear complementarity problem, and this approach has already been used extensively in the circuits and systems community for static networks. In this paper, the object of study will be dynamic electrical circuits that can be recast as linear complementarity systems, i.e., as interconnections of linear time-invariant differential equatio...

  14. Applied linear algebra

    CERN Document Server

    Olver, Peter J

    2018-01-01

    This textbook develops the essential tools of linear algebra, with the goal of imparting technique alongside contextual understanding. Applications go hand-in-hand with theory, each reinforcing and explaining the other. This approach encourages students to develop not only the technical proficiency needed to go on to further study, but an appreciation for when, why, and how the tools of linear algebra can be used across modern applied mathematics. Providing an extensive treatment of essential topics such as Gaussian elimination, inner products and norms, and eigenvalues and singular values, this text can be used for an in-depth first course, or an application-driven second course in linear algebra. In this second edition, applications have been updated and expanded to include numerical methods, dynamical systems, data analysis, and signal processing, while the pedagogical flow of the core material has been improved. Throughout, the text emphasizes the conceptual connections between each application and the un...

  15. Application of quasi-optical approach to construct RF power supply for TeV linear colliders

    International Nuclear Information System (INIS)

    Saldin, E.L.; Sarantsev, V.P.; Schneidmiller, E.A.; Ulyanov, Yu.N.; Yurkov, M.V.

    1995-01-01

    An idea to use a quasi-optical approach for constructing an RF power supply for TeV linear e + e - colliders is developed. The RF source of the proposed scheme is composed of a large number of low-power RF amplifiers commutated by quasi-optical elements. The RF power of this source is transmitted to the accelerating structure of the collider by means of quasi-optical waveguides and mirrors. Such an approach enables one not only to decrease the required peak RF power by several orders of magnitude with respect to the traditional approach based on standard klystron technique, but also to achieve the required level of reliability, as it is based on well-developed technology of serial microwave devices. To illustrate the proposed scheme, a conceptual project of 2x500 GeV X-band collider is considered. Accelerating structure of the collider is of the standard travelling wave type and the RF source is assumed to be composed of 0.7 MW klystrons. All equipment of such a collider is placed in a tunnel of 12x6 m 2 cross section. It is shown that such a collider may be constructed at the present level of accelerator technique. ((orig.))

  16. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

    Directory of Open Access Journals (Sweden)

    Isabelle Karine da Costa Nunes

    Full Text Available Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448 presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral, 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

  17. Observer Design for Boundary Coupled PDEs

    DEFF Research Database (Denmark)

    Moura, Scott; Bendtsen, Jan Dimon; Ruiz, Victor

    2013-01-01

    observer is derived, which uses only measurements of how many TCLs turn on/off at any given time. The design is proven to be exponentially stable via backstepping techniques. Finally, the observer's properties are demonstrated via simulation examples. The estimator provides system-critical information......This paper develops methods for state estimation of aggregated thermostatically controlled loads (TCLs) in smart grids, via partial differential equation (PDE) techniques. TCLs include on/off controlled devices, such as heat pumps, HVAC systems, and deep freezers. Control of aggregated TCLs...... on designing a state estimation scheme for a PDE-based model of aggregated TCLs, thus reducing the required communication. First, a two-state linear hyperbolic PDE model for homogenous TCL populations is presented. This model is extended to heterogeneous populations by including a diffusive term. Next, a state...

  18. Modeling digital switching circuits with linear algebra

    CERN Document Server

    Thornton, Mitchell A

    2014-01-01

    Modeling Digital Switching Circuits with Linear Algebra describes an approach for modeling digital information and circuitry that is an alternative to Boolean algebra. While the Boolean algebraic model has been wildly successful and is responsible for many advances in modern information technology, the approach described in this book offers new insight and different ways of solving problems. Modeling the bit as a vector instead of a scalar value in the set {0, 1} allows digital circuits to be characterized with transfer functions in the form of a linear transformation matrix. The use of transf

  19. Two linearization methods for atmospheric remote sensing

    International Nuclear Information System (INIS)

    Doicu, A.; Trautmann, T.

    2009-01-01

    We present two linearization methods for a pseudo-spherical atmosphere and general viewing geometries. The first approach is based on an analytical linearization of the discrete ordinate method with matrix exponential and incorporates two models for matrix exponential calculation: the matrix eigenvalue method and the Pade approximation. The second method referred to as the forward-adjoint approach is based on the adjoint radiative transfer for a pseudo-spherical atmosphere. We provide a compact description of the proposed methods as well as a numerical analysis of their accuracy and efficiency.

  20. Numerically pricing American options under the generalized mixed fractional Brownian motion model

    Science.gov (United States)

    Chen, Wenting; Yan, Bowen; Lian, Guanghua; Zhang, Ying

    2016-06-01

    In this paper, we introduce a robust numerical method, based on the upwind scheme, for the pricing of American puts under the generalized mixed fractional Brownian motion (GMFBM) model. By using portfolio analysis and applying the Wick-Itô formula, a partial differential equation (PDE) governing the prices of vanilla options under the GMFBM is successfully derived for the first time. Based on this, we formulate the pricing of American puts under the current model as a linear complementarity problem (LCP). Unlike the classical Black-Scholes (B-S) model or the generalized B-S model discussed in Cen and Le (2011), the newly obtained LCP under the GMFBM model is difficult to be solved accurately because of the numerical instability which results from the degeneration of the governing PDE as time approaches zero. To overcome this difficulty, a numerical approach based on the upwind scheme is adopted. It is shown that the coefficient matrix of the current method is an M-matrix, which ensures its stability in the maximum-norm sense. Remarkably, we have managed to provide a sharp theoretic error estimate for the current method, which is further verified numerically. The results of various numerical experiments also suggest that this new approach is quite accurate, and can be easily extended to price other types of financial derivatives with an American-style exercise feature under the GMFBM model.

  1. Coalizões em educação no Brasil: relação com o governo e influência sobre o Plano de Desenvolvimento da Educação (PDE

    Directory of Open Access Journals (Sweden)

    Lara Elena Ramos Simielli

    2013-06-01

    Full Text Available Atualmente, duas coalizões lutam pela melhoria da qualidade da educação no Brasil: a Campanha Nacional pelo Direito à Educação e o Todos pela Educação. Essas duas coalizões diferenciam-se dos movimentos históricos por sua capacidade de agregar atores provenientes de instituições governamentais e não governamentais, de diversos níveis, que possuem valores e crenças comuns em uma aliança única, aproximando-se do conceito de coalizões advocatórias proposto por Sabatier e Jenkins-Smith (1993. Apesar da bandeira comum, elas possuem origens, composições, metas e formas de atuação completamente diferentes - a relação com o governo é um dos pontos que mais as diferencia. O lançamento do Plano de Desenvolvimento da Educação (PDE, com uma das medidas intitulada "Plano de Metas Compromisso Todos pela Educação", gerou questionamentos com relação à similaridade dos nomes entre um plano de governo e uma das coalizões. Neste artigo, apresentaremos as duas coalizões e a relação de ambas com o governo, utilizando o PDE como estudo de caso.

  2. Using Linear Algebra to Introduce Computer Algebra, Numerical Analysis, Data Structures and Algorithms (and To Teach Linear Algebra, Too).

    Science.gov (United States)

    Gonzalez-Vega, Laureano

    1999-01-01

    Using a Computer Algebra System (CAS) to help with the teaching of an elementary course in linear algebra can be one way to introduce computer algebra, numerical analysis, data structures, and algorithms. Highlights the advantages and disadvantages of this approach to the teaching of linear algebra. (Author/MM)

  3. New approach to solve symmetric fully fuzzy linear systems

    Indian Academy of Sciences (India)

    In this paper, we present a method to solve fully fuzzy linear systems with symmetric coefficient matrix. The symmetric coefficient matrix is decomposed into two systems of equations by using Cholesky method and then a solution can be obtained. Numerical examples are given to illustrate our method.

  4. Timetabling an Academic Department with Linear Programming.

    Science.gov (United States)

    Bezeau, Lawrence M.

    This paper describes an approach to faculty timetabling and course scheduling that uses computerized linear programming. After reviewing the literature on linear programming, the paper discusses the process whereby a timetable was created for a department at the University of New Brunswick. Faculty were surveyed with respect to course offerings…

  5. Non-linear and signal energy optimal asymptotic filter design

    Directory of Open Access Journals (Sweden)

    Josef Hrusak

    2003-10-01

    Full Text Available The paper studies some connections between the main results of the well known Wiener-Kalman-Bucy stochastic approach to filtering problems based mainly on the linear stochastic estimation theory and emphasizing the optimality aspects of the achieved results and the classical deterministic frequency domain linear filters such as Chebyshev, Butterworth, Bessel, etc. A new non-stochastic but not necessarily deterministic (possibly non-linear alternative approach called asymptotic filtering based mainly on the concepts of signal power, signal energy and a system equivalence relation plays an important role in the presentation. Filtering error invariance and convergence aspects are emphasized in the approach. It is shown that introducing the signal power as the quantitative measure of energy dissipation makes it possible to achieve reasonable results from the optimality point of view as well. The property of structural energy dissipativeness is one of the most important and fundamental features of resulting filters. Therefore, it is natural to call them asymptotic filters. The notion of the asymptotic filter is carried in the paper as a proper tool in order to unify stochastic and non-stochastic, linear and nonlinear approaches to signal filtering.

  6. A mixed-integer linear programming approach to the reduction of genome-scale metabolic networks.

    Science.gov (United States)

    Röhl, Annika; Bockmayr, Alexander

    2017-01-03

    Constraint-based analysis has become a widely used method to study metabolic networks. While some of the associated algorithms can be applied to genome-scale network reconstructions with several thousands of reactions, others are limited to small or medium-sized models. In 2015, Erdrich et al. introduced a method called NetworkReducer, which reduces large metabolic networks to smaller subnetworks, while preserving a set of biological requirements that can be specified by the user. Already in 2001, Burgard et al. developed a mixed-integer linear programming (MILP) approach for computing minimal reaction sets under a given growth requirement. Here we present an MILP approach for computing minimum subnetworks with the given properties. The minimality (with respect to the number of active reactions) is not guaranteed by NetworkReducer, while the method by Burgard et al. does not allow specifying the different biological requirements. Our procedure is about 5-10 times faster than NetworkReducer and can enumerate all minimum subnetworks in case there exist several ones. This allows identifying common reactions that are present in all subnetworks, and reactions appearing in alternative pathways. Applying complex analysis methods to genome-scale metabolic networks is often not possible in practice. Thus it may become necessary to reduce the size of the network while keeping important functionalities. We propose a MILP solution to this problem. Compared to previous work, our approach is more efficient and allows computing not only one, but even all minimum subnetworks satisfying the required properties.

  7. An Ionospheric Index Model based on Linear Regression and Neural Network Approaches

    Science.gov (United States)

    Tshisaphungo, Mpho; McKinnell, Lee-Anne; Bosco Habarulema, John

    2017-04-01

    The ionosphere is well known to reflect radio wave signals in the high frequency (HF) band due to the present of electron and ions within the region. To optimise the use of long distance HF communications, it is important to understand the drivers of ionospheric storms and accurately predict the propagation conditions especially during disturbed days. This paper presents the development of an ionospheric storm-time index over the South African region for the application of HF communication users. The model will result into a valuable tool to measure the complex ionospheric behaviour in an operational space weather monitoring and forecasting environment. The development of an ionospheric storm-time index is based on a single ionosonde station data over Grahamstown (33.3°S,26.5°E), South Africa. Critical frequency of the F2 layer (foF2) measurements for a period 1996-2014 were considered for this study. The model was developed based on linear regression and neural network approaches. In this talk validation results for low, medium and high solar activity periods will be discussed to demonstrate model's performance.

  8. Parameter Estimation of Partial Differential Equation Models.

    Science.gov (United States)

    Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J; Maity, Arnab

    2013-01-01

    Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data.

  9. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-07-01

    Full Text Available Abstract Inhaled prostanoids and phosphodiesterase (PDE inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor, motapizone (PDE3 inhibitor or 8-Methoxymethyl-IBMX (PDE1 inhibitor synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.

  10. LINEAR2007, Linear-Linear Interpolation of ENDF Format Cross-Sections

    International Nuclear Information System (INIS)

    2007-01-01

    1 - Description of program or function: LINEAR converts evaluated cross sections in the ENDF/B format into a tabular form that is subject to linear-linear interpolation in energy and cross section. The code also thins tables of cross sections already in that form. Codes used subsequently need thus to consider only linear-linear data. IAEA1311/15: This version include the updates up to January 30, 2007. Changes in ENDF/B-VII Format and procedures, as well as the evaluations themselves, make it impossible for versions of the ENDF/B pre-processing codes earlier than PREPRO 2007 (2007 Version) to accurately process current ENDF/B-VII evaluations. The present code can handle all existing ENDF/B-VI evaluations through release 8, which will be the last release of ENDF/B-VI. Modifications from previous versions: - Linear VERS. 2007-1 (JAN. 2007): checked against all ENDF/B-VII; increased page size from 60,000 to 600,000 points 2 - Method of solution: Each section of data is considered separately. Each section of File 3, 23, and 27 data consists of a table of cross section versus energy with any of five interpolation laws. LINEAR will replace each section with a new table of energy versus cross section data in which the interpolation law is always linear in energy and cross section. The histogram (constant cross section between two energies) interpolation law is converted to linear-linear by substituting two points for each initial point. The linear-linear is not altered. For the log-linear, linear-log and log- log laws, the cross section data are converted to linear by an interval halving algorithm. Each interval is divided in half until the value at the middle of the interval can be approximated by linear-linear interpolation to within a given accuracy. The LINEAR program uses a multipoint fractional error thinning algorithm to minimize the size of each cross section table

  11. An Efficacious Multi-Objective Fuzzy Linear Programming Approach for Optimal Power Flow Considering Distributed Generation.

    Science.gov (United States)

    Warid, Warid; Hizam, Hashim; Mariun, Norman; Abdul-Wahab, Noor Izzri

    2016-01-01

    This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality.

  12. The Effect of Creative Tasks on Electrocardiogram: Using Linear and Nonlinear Features in Combination with Classification Approaches

    Directory of Open Access Journals (Sweden)

    Sahar Zakeri

    2017-02-01

    Full Text Available Objective: Interest in the subject of creativity and its impacts on human life is growing extensively. However, only a few surveys pay attention to the relation between creativity and physiological changes. This paper presents a novel approach to distinguish between creativity states from electrocardiogram signals. Nineteen linear and nonlinear features of the cardiac signal were extracted to detect creativity states. Method: ECG signals of 52 participants were recorded while doing three tasks of Torrance Tests of Creative Thinking (TTCT/ figural B. To remove artifacts, notch filter 50 Hz and Chebyshev II were applied. According to TTCT scores, participants were categorized into the high and low creativity groups: Participants with scores higher than 70 were assigned into the high creativity group and those with scores less than 30 were considered as low creativity group. Some linear and nonlinear features were extracted from the ECGs. Then, Support Vector Machine (SVM and Adaptive Neuro-Fuzzy Inference System (ANFIS were used to classify the groups.Results: Applying the Wilcoxon test, significant differences were observed between rest and each three tasks of creativity. However, better discrimination was performed between rest and the first task. In addition, there were no statistical differences between the second and third task of the test. The results indicated that the SVM effectively detects all the three tasks from the rest, particularly the task 1 and reached the maximum accuracy of 99.63% in the linear analysis. In addition, the high creative group was separated from the low creative group with the accuracy of 98.41%.Conclusion: the combination of SVM classifier with linear features can be useful to show the relation between creativity and physiological changes.

  13. Krylov Subspace Methods for Complex Non-Hermitian Linear Systems. Thesis

    Science.gov (United States)

    Freund, Roland W.

    1991-01-01

    We consider Krylov subspace methods for the solution of large sparse linear systems Ax = b with complex non-Hermitian coefficient matrices. Such linear systems arise in important applications, such as inverse scattering, numerical solution of time-dependent Schrodinger equations, underwater acoustics, eddy current computations, numerical computations in quantum chromodynamics, and numerical conformal mapping. Typically, the resulting coefficient matrices A exhibit special structures, such as complex symmetry, or they are shifted Hermitian matrices. In this paper, we first describe a Krylov subspace approach with iterates defined by a quasi-minimal residual property, the QMR method, for solving general complex non-Hermitian linear systems. Then, we study special Krylov subspace methods designed for the two families of complex symmetric respectively shifted Hermitian linear systems. We also include some results concerning the obvious approach to general complex linear systems by solving equivalent real linear systems for the real and imaginary parts of x. Finally, numerical experiments for linear systems arising from the complex Helmholtz equation are reported.

  14. Non-linear aeroelastic prediction for aircraft applications

    Science.gov (United States)

    de C. Henshaw, M. J.; Badcock, K. J.; Vio, G. A.; Allen, C. B.; Chamberlain, J.; Kaynes, I.; Dimitriadis, G.; Cooper, J. E.; Woodgate, M. A.; Rampurawala, A. M.; Jones, D.; Fenwick, C.; Gaitonde, A. L.; Taylor, N. V.; Amor, D. S.; Eccles, T. A.; Denley, C. J.

    2007-05-01

    Current industrial practice for the prediction and analysis of flutter relies heavily on linear methods and this has led to overly conservative design and envelope restrictions for aircraft. Although the methods have served the industry well, it is clear that for a number of reasons the inclusion of non-linearity in the mathematical and computational aeroelastic prediction tools is highly desirable. The increase in available and affordable computational resources, together with major advances in algorithms, mean that non-linear aeroelastic tools are now viable within the aircraft design and qualification environment. The Partnership for Unsteady Methods in Aerodynamics (PUMA) Defence and Aerospace Research Partnership (DARP) was sponsored in 2002 to conduct research into non-linear aeroelastic prediction methods and an academic, industry, and government consortium collaborated to address the following objectives: To develop useable methodologies to model and predict non-linear aeroelastic behaviour of complete aircraft. To evaluate the methodologies on real aircraft problems. To investigate the effect of non-linearities on aeroelastic behaviour and to determine which have the greatest effect on the flutter qualification process. These aims have been very effectively met during the course of the programme and the research outputs include: New methods available to industry for use in the flutter prediction process, together with the appropriate coaching of industry engineers. Interesting results in both linear and non-linear aeroelastics, with comprehensive comparison of methods and approaches for challenging problems. Additional embryonic techniques that, with further research, will further improve aeroelastics capability. This paper describes the methods that have been developed and how they are deployable within the industrial environment. We present a thorough review of the PUMA aeroelastics programme together with a comprehensive review of the relevant research

  15. Comparison of linear, mixed integer and non-linear programming methods in energy system dispatch modelling

    DEFF Research Database (Denmark)

    Ommen, Torben Schmidt; Markussen, Wiebke Brix; Elmegaard, Brian

    2014-01-01

    In the paper, three frequently used operation optimisation methods are examined with respect to their impact on operation management of the combined utility technologies for electric power and DH (district heating) of eastern Denmark. The investigation focusses on individual plant operation...... differences and differences between the solution found by each optimisation method. One of the investigated approaches utilises LP (linear programming) for optimisation, one uses LP with binary operation constraints, while the third approach uses NLP (non-linear programming). The LP model is used...... as a benchmark, as this type is frequently used, and has the lowest amount of constraints of the three. A comparison of the optimised operation of a number of units shows significant differences between the three methods. Compared to the reference, the use of binary integer variables, increases operation...

  16. Modeling the thermal behavior of fluid flow inside channels using an artificial locally linear neuro-fuzzy approach

    Directory of Open Access Journals (Sweden)

    Azadeh Hashemian

    2008-06-01

    Full Text Available Enhanced surface heat exchangers are commonly used all worldwide. If applicable, due to their complicated geometry, simulating corrugated plate heat exchangers is a time-consuming process. In the present study, first we simulate the heat transfer in a sharp V-shape corrugation cell with constant temperature walls; then, we use a Locally Linear Neuro-Fuzzy method based on a radial basis function (RBFs to model the temperature field in the whole channel. New approach is developed to deal with fast computational and low memory resources that can be used with the largest available data sets. The purpose of the research is to reveal the advantages of proposed Neuro-Fuzzy model as a powerful modeling system designed for predicting and to make a fair comparison between it and the successful FLUENT simulated approaches in its best structures.

  17. Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit, orange (SINETROL) in human body fat adipocytes. Mechanism of action by inhibition of cAMP-phosphodiesterase (PDE).

    Science.gov (United States)

    Dallas, Constantin; Gerbi, Alain; Tenca, Guillaume; Juchaux, Franck; Bernard, François-Xavier

    2008-10-01

    The present study investigated the lipolytic (break of fat stored) effect of a citrus-based polyphenolic dietary supplement (SINETROL) at human adipocytes (ex vivo), body fat (clinical) and biochemical levels (inhibition of phosphodiesterase). Free fatty acids (FFA) release was used as indicator of human adipocyte lipolysis and SINETROL activity has been compared with known lipolytic products (isoproterenol, theopylline and caffeine). SINETROL stimulated significantly the lipolytic activity in a range of 6 fold greater than the control. Moreover, SINETROL has 2.1 greater activity than guarana 12% caffeine while its content in caffeine is 3 times lower. Clinically, two groups of 10 volunteers with BMI relevant of overweight were compared during 4 and 12 weeks with 1.4 g/day SINETROL and placebo supplementation. In the SINETROL Group the body fat (%) decreased with a significant difference of 5.53% and 15.6% after 4 and 12 weeks, respectively, while the body weight (kg) decreased with a significant difference of 2.2 and 5.2 kg after 4 and 12 weeks, respectively. These observed effects are linked to SINETROL polyphenolic composition and its resulting synergistic activity. SINETROL is a potent inhibitor of cAMP-phosphodiesterase (PDE) (97%) compared to other purified compounds (cyanidin-3 glycoside, narangin, caffeine). These results suggest that SINETROL has a strong lipolytic effect mediated by cAMP-PDE inhibition. SINETROL may serve to prevent obesity by decreasing BMI.

  18. Hyperspectral and multispectral data fusion based on linear-quadratic nonnegative matrix factorization

    Science.gov (United States)

    Benhalouche, Fatima Zohra; Karoui, Moussa Sofiane; Deville, Yannick; Ouamri, Abdelaziz

    2017-04-01

    This paper proposes three multisharpening approaches to enhance the spatial resolution of urban hyperspectral remote sensing images. These approaches, related to linear-quadratic spectral unmixing techniques, use a linear-quadratic nonnegative matrix factorization (NMF) multiplicative algorithm. These methods begin by unmixing the observable high-spectral/low-spatial resolution hyperspectral and high-spatial/low-spectral resolution multispectral images. The obtained high-spectral/high-spatial resolution features are then recombined, according to the linear-quadratic mixing model, to obtain an unobservable multisharpened high-spectral/high-spatial resolution hyperspectral image. In the first designed approach, hyperspectral and multispectral variables are independently optimized, once they have been coherently initialized. These variables are alternately updated in the second designed approach. In the third approach, the considered hyperspectral and multispectral variables are jointly updated. Experiments, using synthetic and real data, are conducted to assess the efficiency, in spatial and spectral domains, of the designed approaches and of linear NMF-based approaches from the literature. Experimental results show that the designed methods globally yield very satisfactory spectral and spatial fidelities for the multisharpened hyperspectral data. They also prove that these methods significantly outperform the used literature approaches.

  19. Linear approximation model network and its formation via ...

    Indian Academy of Sciences (India)

    To overcome the deficiency of `local model network' (LMN) techniques, an alternative `linear approximation model' (LAM) network approach is proposed. Such a network models a nonlinear or practical system with multiple linear models fitted along operating trajectories, where individual models are simply networked ...

  20. On the dynamic analysis of piecewise-linear networks

    NARCIS (Netherlands)

    Heemels, WPMH; Camlibel, MK; Schumacher, JM

    Piecewise-linear (PL) modeling is often used to approximate the behavior of nonlinear circuits. One of the possible PL modeling methodologies is based on the linear complementarity problem, and this approach has already been used extensively in the circuits and systems community for static networks.

  1. A note on probabilistic models over strings: the linear algebra approach.

    Science.gov (United States)

    Bouchard-Côté, Alexandre

    2013-12-01

    Probabilistic models over strings have played a key role in developing methods that take into consideration indels as phylogenetically informative events. There is an extensive literature on using automata and transducers on phylogenies to do inference on these probabilistic models, in which an important theoretical question is the complexity of computing the normalization of a class of string-valued graphical models. This question has been investigated using tools from combinatorics, dynamic programming, and graph theory, and has practical applications in Bayesian phylogenetics. In this work, we revisit this theoretical question from a different point of view, based on linear algebra. The main contribution is a set of results based on this linear algebra view that facilitate the analysis and design of inference algorithms on string-valued graphical models. As an illustration, we use this method to give a new elementary proof of a known result on the complexity of inference on the "TKF91" model, a well-known probabilistic model over strings. Compared to previous work, our proving method is easier to extend to other models, since it relies on a novel weak condition, triangular transducers, which is easy to establish in practice. The linear algebra view provides a concise way of describing transducer algorithms and their compositions, opens the possibility of transferring fast linear algebra libraries (for example, based on GPUs), as well as low rank matrix approximation methods, to string-valued inference problems.

  2. Non-linear wave equations:Mathematical techniques

    International Nuclear Information System (INIS)

    1978-01-01

    An account of certain well-established mathematical methods, which prove useful to deal with non-linear partial differential equations is presented. Within the strict framework of Functional Analysis, it describes Semigroup Techniques in Banach Spaces as well as variational approaches towards critical points. Detailed proofs are given of the existence of local and global solutions of the Cauchy problem and of the stability of stationary solutions. The formal approach based upon invariance under Lie transformations deserves attention due to its wide range of applicability, even if the explicit solutions thus obtained do not allow for a deep analysis of the equations. A compre ensive introduction to the inverse scattering approach and to the solution concept for certain non-linear equations of physical interest are also presented. A detailed discussion is made about certain convergence and stability problems which arise in importance need not be emphasized. (author) [es

  3. Linearization Method and Linear Complexity

    Science.gov (United States)

    Tanaka, Hidema

    We focus on the relationship between the linearization method and linear complexity and show that the linearization method is another effective technique for calculating linear complexity. We analyze its effectiveness by comparing with the logic circuit method. We compare the relevant conditions and necessary computational cost with those of the Berlekamp-Massey algorithm and the Games-Chan algorithm. The significant property of a linearization method is that it needs no output sequence from a pseudo-random number generator (PRNG) because it calculates linear complexity using the algebraic expression of its algorithm. When a PRNG has n [bit] stages (registers or internal states), the necessary computational cost is smaller than O(2n). On the other hand, the Berlekamp-Massey algorithm needs O(N2) where N(≅2n) denotes period. Since existing methods calculate using the output sequence, an initial value of PRNG influences a resultant value of linear complexity. Therefore, a linear complexity is generally given as an estimate value. On the other hand, a linearization method calculates from an algorithm of PRNG, it can determine the lower bound of linear complexity.

  4. Electronic excitation of atoms and molecules by electron impact in a linear algebraic, separable potential approach

    International Nuclear Information System (INIS)

    Collins, L.A.; Schneider, B.I.

    1984-01-01

    The linear algebraic, separable potential approach is applied to the electronic excitation of atoms and molecules by electron impact. By representing the exchange and off-diagonal direct terms on a basis, the standard set of coupled inelastic equations is reduced to a set of elastic inhomogeneous equations. The procedure greatly simplifies the formulation by allowing a large portion of the problem to be handled by standard bound-state techniques and by greatly reducing the order of the scattering equations that must be solved. Application is made to the excitation of atomic hydrogen in the three-state close-coupling (1s, 2s, 2p) approximation. (author)

  5. Composite Linear Models | Division of Cancer Prevention

    Science.gov (United States)

    By Stuart G. Baker The composite linear models software is a matrix approach to compute maximum likelihood estimates and asymptotic standard errors for models for incomplete multinomial data. It implements the method described in Baker SG. Composite linear models for incomplete multinomial data. Statistics in Medicine 1994;13:609-622. The software includes a library of thirty

  6. Basic linear partial differential equations

    CERN Document Server

    Treves, Francois

    1975-01-01

    Focusing on the archetypes of linear partial differential equations, this text for upper-level undergraduates and graduate students features most of the basic classical results. The methods, however, are decidedly nontraditional: in practically every instance, they tend toward a high level of abstraction. This approach recalls classical material to contemporary analysts in a language they can understand, as well as exploiting the field's wealth of examples as an introduction to modern theories.The four-part treatment covers the basic examples of linear partial differential equations and their

  7. A generalized linear factor model approach to the hierarchical framework for responses and response times.

    Science.gov (United States)

    Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

    2015-05-01

    We show how the hierarchical model for responses and response times as developed by van der Linden (2007), Fox, Klein Entink, and van der Linden (2007), Klein Entink, Fox, and van der Linden (2009), and Glas and van der Linden (2010) can be simplified to a generalized linear factor model with only the mild restriction that there is no hierarchical model at the item side. This result is valuable as it enables all well-developed modelling tools and extensions that come with these methods. We show that the restriction we impose on the hierarchical model does not influence parameter recovery under realistic circumstances. In addition, we present two illustrative real data analyses to demonstrate the practical benefits of our approach. © 2014 The British Psychological Society.

  8. IceTrendr: a linear time-series approach to monitoring glacier environments using Landsat

    Science.gov (United States)

    Nelson, P.; Kennedy, R. E.; Nolin, A. W.; Hughes, J. M.; Braaten, J.

    2017-12-01

    Arctic glaciers in Alaska and Canada have experienced some of the greatest ice mass loss of any region in recent decades. A challenge to understanding these changing ecosystems, however, is developing globally-consistent, multi-decadal monitoring of glacier ice. We present a toolset and approach that captures, labels, and maps glacier change for use in climate science, hydrology, and Earth science education using Landsat Time Series (LTS). The core step is "temporal segmentation," wherein a yearly LTS is cleaned using pre-processing steps, converted to a snow/ice index, and then simplified into the salient shape of the change trajectory ("temporal signature") using linear segmentation. Such signatures can be characterized as simple `stable' or `transition of glacier ice to rock' to more complex multi-year changes like `transition of glacier ice to debris-covered glacier ice to open water to bare rock to vegetation'. This pilot study demonstrates the potential for interactively mapping, visualizing, and labeling glacier changes. What is truly innovative is that IceTrendr not only maps the changes but also uses expert knowledge to label the changes and such labels can be applied to other glaciers exhibiting statistically similar temporal signatures. Our key findings are that the IceTrendr concept and software can provide important functionality for glaciologists and educators interested in studying glacier changes during the Landsat TM timeframe (1984-present). Issues of concern with using dense Landsat time-series approaches for glacier monitoring include many missing images during the period 1984-1995 and that automated cloud mask are challenged and require the user to manually identify cloud-free images. IceTrendr is much more than just a simple "then and now" approach to glacier mapping. This process is a means of integrating the power of computing, remote sensing, and expert knowledge to "tell the story" of glacier changes.

  9. Introduction to partial differential equations

    CERN Document Server

    Borthwick, David

    2016-01-01

    This modern take on partial differential equations does not require knowledge beyond vector calculus and linear algebra. The author focuses on the most important classical partial differential equations, including conservation equations and their characteristics, the wave equation, the heat equation, function spaces, and Fourier series, drawing on tools from analysis only as they arise.Within each section the author creates a narrative that answers the five questions: (1) What is the scientific problem we are trying to understand? (2) How do we model that with PDE? (3) What techniques can we use to analyze the PDE? (4) How do those techniques apply to this equation? (5) What information or insight did we obtain by developing and analyzing the PDE? The text stresses the interplay between modeling and mathematical analysis, providing a thorough source of problems and an inspiration for the development of methods.

  10. Robust control and linear parameter varying approaches application to vehicle dynamics

    CERN Document Server

    Gaspar, Peter; Bokor, József

    2013-01-01

    Vehicles are complex systems (non-linear, multi-variable) where the abundance of embedded controllers should ensure better security. This book aims at emphasizing the interest and potential of Linear Parameter Varying methods within the framework of vehicle dynamics, e.g.   ·          proposed control-oriented model, complex enough to handle some system non linearities but still simple for control or observer design,   ·          take into account the adaptability of the vehicle's response to driving situations, to the driver request and/or to the road sollicitations,   ·          manage interactions between various actuators to optimize the dynamic behavior of vehicles.   This book results from the 32th International Summer School in Automatic that held in Grenoble, France, in September 2011, where recent methods (based on robust control and LPV technics), then applied to the control of vehicle dynamics, have been presented. After some theoretical background and a view on so...

  11. Linear network error correction coding

    CERN Document Server

    Guang, Xuan

    2014-01-01

    There are two main approaches in the theory of network error correction coding. In this SpringerBrief, the authors summarize some of the most important contributions following the classic approach, which represents messages by sequences?similar to algebraic coding,?and also briefly discuss the main results following the?other approach,?that uses the theory of rank metric codes for network error correction of representing messages by subspaces. This book starts by establishing the basic linear network error correction (LNEC) model and then characterizes two equivalent descriptions. Distances an

  12. Deterministic linear-optics quantum computing based on a hybrid approach

    International Nuclear Information System (INIS)

    Lee, Seung-Woo; Jeong, Hyunseok

    2014-01-01

    We suggest a scheme for all-optical quantum computation using hybrid qubits. It enables one to efficiently perform universal linear-optical gate operations in a simple and near-deterministic way using hybrid entanglement as off-line resources

  13. Deterministic linear-optics quantum computing based on a hybrid approach

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Woo; Jeong, Hyunseok [Center for Macroscopic Quantum Control, Department of Physics and Astronomy, Seoul National University, Seoul, 151-742 (Korea, Republic of)

    2014-12-04

    We suggest a scheme for all-optical quantum computation using hybrid qubits. It enables one to efficiently perform universal linear-optical gate operations in a simple and near-deterministic way using hybrid entanglement as off-line resources.

  14. Gain scheduled linear quadratic control for quadcopter

    Science.gov (United States)

    Okasha, M.; Shah, J.; Fauzi, W.; Hanouf, Z.

    2017-12-01

    This study exploits the dynamics and control of quadcopters using Linear Quadratic Regulator (LQR) control approach. The quadcopter’s mathematical model is derived using the Newton-Euler method. It is a highly manoeuvrable, nonlinear, coupled with six degrees of freedom (DOF) model, which includes aerodynamics and detailed gyroscopic moments that are often ignored in many literatures. The linearized model is obtained and characterized by the heading angle (i.e. yaw angle) of the quadcopter. The adopted control approach utilizes LQR method to track several reference trajectories including circle and helix curves with significant variation in the yaw angle. The controller is modified to overcome difficulties related to the continuous changes in the operating points and eliminate chattering and discontinuity that is observed in the control input signal. Numerical non-linear simulations are performed using MATLAB and Simulink to illustrate to accuracy and effectiveness of the proposed controller.

  15. Linear feedback controls the essentials

    CERN Document Server

    Haidekker, Mark A

    2013-01-01

    The design of control systems is at the very core of engineering. Feedback controls are ubiquitous, ranging from simple room thermostats to airplane engine control. Helping to make sense of this wide-ranging field, this book provides a new approach by keeping a tight focus on the essentials with a limited, yet consistent set of examples. Analysis and design methods are explained in terms of theory and practice. The book covers classical, linear feedback controls, and linear approximations are used when needed. In parallel, the book covers time-discrete (digital) control systems and juxtapos

  16. Approach for Self-Calibrating CO2 Measurements with Linear Membrane-Based Gas Sensors

    Directory of Open Access Journals (Sweden)

    Detlef Lazik

    2016-11-01

    Full Text Available Linear membrane-based gas sensors that can be advantageously applied for the measurement of a single gas component in large heterogeneous systems, e.g., for representative determination of CO2 in the subsurface, can be designed depending on the properties of the observation object. A resulting disadvantage is that the permeation-based sensor response depends on operating conditions, the individual site-adapted sensor geometry, the membrane material, and the target gas component. Therefore, calibration is needed, especially of the slope, which could change over several orders of magnitude. A calibration-free approach based on an internal gas standard is developed to overcome the multi-criterial slope dependency. This results in a normalization of sensor response and enables the sensor to assess the significance of measurement. The approach was proofed on the example of CO2 analysis in dry air with tubular PDMS membranes for various CO2 concentrations of an internal standard. Negligible temperature dependency was found within an 18 K range. The transformation behavior of the measurement signal and the influence of concentration variations of the internal standard on the measurement signal were shown. Offsets that were adjusted based on the stated theory for the given measurement conditions and material data from the literature were in agreement with the experimentally determined offsets. A measurement comparison with an NDIR reference sensor shows an unexpectedly low bias (<1% of the non-calibrated sensor response, and comparable statistical uncertainty.

  17. Linear and integer programming made easy

    CERN Document Server

    Hu, T C

    2016-01-01

    Linear and integer programming are fundamental toolkits for data and information science and technology, particularly in the context of today’s megatrends toward statistical optimization, machine learning, and big data analytics. Drawn from over 30 years of classroom teaching and applied research experience, this textbook provides a crisp and practical introduction to the basics of linear and integer programming. The authors’ approach is accessible to students from all fields of engineering, including operations research, statistics, machine learning, control system design, scheduling, formal verification, and computer vision. Readers will learn to cast hard combinatorial problems as mathematical programming optimizations, understand how to achieve formulations where the objective and constraints are linear, choose appropriate solution methods, and interpret results appropriately. •Provides a concise introduction to linear and integer programming, appropriate for undergraduates, graduates, a short cours...

  18. Fourier imaging of non-linear structure formation

    Energy Technology Data Exchange (ETDEWEB)

    Brandbyge, Jacob; Hannestad, Steen, E-mail: jacobb@phys.au.dk, E-mail: sth@phys.au.dk [Department of Physics and Astronomy, University of Aarhus, Ny Munkegade 120, DK-8000 Aarhus C (Denmark)

    2017-04-01

    We perform a Fourier space decomposition of the dynamics of non-linear cosmological structure formation in ΛCDM models. From N -body simulations involving only cold dark matter we calculate 3-dimensional non-linear density, velocity divergence and vorticity Fourier realizations, and use these to calculate the fully non-linear mode coupling integrals in the corresponding fluid equations. Our approach allows for a reconstruction of the amount of mode coupling between any two wavenumbers as a function of redshift. With our Fourier decomposition method we identify the transfer of power from larger to smaller scales, the stable clustering regime, the scale where vorticity becomes important, and the suppression of the non-linear divergence power spectrum as compared to linear theory. Our results can be used to improve and calibrate semi-analytical structure formation models.

  19. Fourier imaging of non-linear structure formation

    International Nuclear Information System (INIS)

    Brandbyge, Jacob; Hannestad, Steen

    2017-01-01

    We perform a Fourier space decomposition of the dynamics of non-linear cosmological structure formation in ΛCDM models. From N -body simulations involving only cold dark matter we calculate 3-dimensional non-linear density, velocity divergence and vorticity Fourier realizations, and use these to calculate the fully non-linear mode coupling integrals in the corresponding fluid equations. Our approach allows for a reconstruction of the amount of mode coupling between any two wavenumbers as a function of redshift. With our Fourier decomposition method we identify the transfer of power from larger to smaller scales, the stable clustering regime, the scale where vorticity becomes important, and the suppression of the non-linear divergence power spectrum as compared to linear theory. Our results can be used to improve and calibrate semi-analytical structure formation models.

  20. Progress on $e^{+}e^{-}$ linear colliders

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Siemann, Peter

    2002-01-01

    Physics issues. The physics program will be reviewed for e+e- linear colliders in the TeV energy range. At these prospective facilities central issues of particle physics can be addressed, the problem of mass, unification and structure of space-time. In this context the two lectures will focus on analyses of the Higgs mechanism, supersymmetry and extra space dimensions. Moreover, high-precision studies of the top-quark and the gauge boson sector will be discussed. Combined with LHC results, a comprehensive picture can be developed of physics at the electroweak scale and beyond. Designs and technologies (R. Siemann - 29, 30, 31 May) The physics and technologies of high energy linear colliders will be reviewed. Fundamental concepts of linear colliders will be introduced. They will be discussed in: the context of the Stanford Linear Collider where many ideas changed and new ones were developed in response to operational experience. the requirements for future linear colliders. The different approaches for reac...

  1. Direct torque control via feedback linearization for permanent magnet synchronous motor drives

    DEFF Research Database (Denmark)

    Lascu, Cristian; Boldea, Ion; Blaabjerg, Frede

    2012-01-01

    The paper describes a direct torque controlled (DTC) permanent magnet synchronous motor (PMSM) drive that employs feedback linearization and uses sliding-mode and linear controllers. We introduce a new feedback linearization approach that yields a decoupled linear PMSM model with two state...

  2. Multi-criteria approach with linear combination technique and analytical hierarchy process in land evaluation studies

    Directory of Open Access Journals (Sweden)

    Orhan Dengiz

    2018-01-01

    Full Text Available Land evaluation analysis is a prerequisite to achieving optimum utilization of the available land resources. Lack of knowledge on best combination of factors that suit production of yields has contributed to the low production. The aim of this study was to determine the most suitable areas for agricultural uses. For that reasons, in order to determine land suitability classes of the study area, multi-criteria approach was used with linear combination technique and analytical hierarchy process by taking into consideration of some land and soil physico-chemical characteristic such as slope, texture, depth, derange, stoniness, erosion, pH, EC, CaCO3 and organic matter. These data and land mapping unites were taken from digital detailed soil map scaled as 1:5.000. In addition, in order to was produce land suitability map GIS was program used for the study area. This study was carried out at Mahmudiye, Karaamca, Yazılı, Çiçeközü, Orhaniye and Akbıyık villages in Yenişehir district of Bursa province. Total study area is 7059 ha. 6890 ha of total study area has been used as irrigated agriculture, dry farming agriculture, pasture while, 169 ha has been used for non-agricultural activities such as settlement, road water body etc. Average annual temperature and precipitation of the study area are 16.1oC and 1039.5 mm, respectively. Finally after determination of land suitability distribution classes for the study area, it was found that 15.0% of the study area has highly (S1 and moderately (S2 while, 85% of the study area has marginally suitable and unsuitable coded as S3 and N. It was also determined some relation as compared results of linear combination technique with other hierarchy approaches such as Land Use Capability Classification and Suitability Class for Agricultural Use methods.

  3. A FEM-Experimental Approach for the Development of a Conceptual Linear Actuator Based on Tendril’s Free Coiling

    Directory of Open Access Journals (Sweden)

    Luca Cortese

    2017-01-01

    Full Text Available Within the vastness of the plant species, certain living systems show tendril structures whose motion is of particular interest for biomimetic engineers. Tendrils sense and coil around suitable grips, and by shortening in length, they erect the remaining plant body. To achieve contraction, tendrils rotate along their main axis and shift from a linear to a double-spring geometry. This phenomenon is denoted as the free-coiling phase. In this work, with the aim of understanding the fundamentals of the mechanics behind the free coiling, a reverse-engineering approach based on the finite element method was firstly applied. The model consisted of an elongated cylinder with suitable material properties, boundary, and loading conditions, in order to reproduce the kinematics of the tendril. The simulation succeeded in mimicking coiling faithfully and was therefore used to validate a tentative linear actuator model based on the plant’s working principle. More in detail, exploiting shape memory alloy materials to obtain large reversible deformations, the main tendril features were implemented into a nickel-titanium spring-based testing model. The results of the experimental tests confirmed the feasibility of the idea in terms of both functioning principles and actual performance. It can be concluded that the final set-up can be used as a base for a prototype design of a new kind of a linear actuator.

  4. RANSAC approach for automated registration of terrestrial laser scans using linear features

    Directory of Open Access Journals (Sweden)

    K. Al-Durgham

    2013-10-01

    Full Text Available The registration process of terrestrial laser scans (TLS targets the problem of how to combine several laser scans in order to attain better information about features than what could be obtained through single scan. The main goal of the registration process is to estimate the parameters which determine geometrical variation between the origins of datasets collected from different locations. Scale, shifts, and rotation parameters are usually used to describe such variation. This paper presents a framework for the registration of overlapping terrestrial laser scans by establishing an automatic matching strategy that uses 3D linear features. More specifically, invariant separation characteristics between 3D linear features extracted from laser scans will be used to establish hypothesized conjugate linear features between the laser scans. These candidate matches are then used to geo-reference scans relative to a common reference frame. The registration workflow simulates the well-known RANndom Sample Consensus method (RANSAC for determining the registration parameters, whereas the iterative closest projected point (ICPP is utilized to determine the most probable solution of the transformation parameters from several solutions. The experimental results prove that the proposed methodology can be used for the automatic registration of terrestrial laser scans using linear features.

  5. Linear Programming Approaches for Power Savings in Software-defined Networks

    NARCIS (Netherlands)

    Moghaddam, F.A.; Grosso, P.

    2016-01-01

    Software-defined networks have been proposed as a viable solution to decrease the power consumption of the networking component in data center networks. Still the question remains on which scheduling algorithms are most suited to achieve this goal. We propose 4 different linear programming

  6. Kinetics of oriented crystallization of polymers in the linear stress-orientation range in the series expansion approach

    Directory of Open Access Journals (Sweden)

    L. Jarecki

    2018-04-01

    Full Text Available An analytical formula is derived for the oriented crystallization coefficient governing kinetics of oriented crystallization under uniaxial amorphous orientation in the entire temperature range. A series expansion approach is applied to the free energy of crystallization in the Hoffman-Lauritzen kinetic model of crystallization at accounting for the entropy of orientation of the amorphous chains. The series expansion coefficients are calculated for systems of Gaussian chains in linear stress-orientation range. Oriented crystallization rate functions are determined basing on the ‘proportional expansion’ approach proposed by Ziabicki in the steady-state limit. Crystallization kinetics controlled by separate predetermined and sporadic primary nucleation is considered, as well as the kinetics involving both nucleation mechanisms potentially present in oriented systems. The involvement of sporadic nucleation in the transformation kinetics is predicted to increase with increasing amorphous orientation. Example computations illustrate the dependence of the calculated functions on temperature and amorphous orientation, as well as qualitative agreement of the calculations with experimental results.

  7. Feasibility of non-linear simulation for Field II using an angular spectrum approach

    DEFF Research Database (Denmark)

    Du, Yigang; Jensen, Jørgen Arendt

    2008-01-01

    this procedure is to find the accuracy of the approach for linear propagation, where the result can be validated using Field II simulations. The ASA calculations are carried out by 3D fast Fourier transform using Matlab, where lambda=2 is chosen as the spatial sampling rate to reduce aliasing errors. Zero......-padding is applied to enlarge the source plane to a (4N - 1) times (4N - 1) matrix to overcome artifacts in terms of the circular convolution. The source plane covering an area of 9 times 9 mm2 with N = 61 samples along both side, is 0.05 mm away from a 5 MHz planar piston transducer, which is simulated by Field II....... To determine the accuracy, different sampling intervals and zero-paddings are compared and the errors are calculated with Field II as a reference. It can be seen that zero-padding with 4N - 1 and lambda=2 sampling can both reduce the errors from 25.7% to 12.9% for the near-field and from 18.1% to 5...

  8. A Nutritional Analysis of the Food Basket in BIH: A Linear Programming Approach

    Directory of Open Access Journals (Sweden)

    Arnaut-Berilo Almira

    2017-04-01

    Full Text Available This paper presents linear and goal programming optimization models for determining and analyzing the food basket in Bosnia and Herzegovina (BiH in terms of adequate nutritional needs according to World Health Organization (WHO standards and World Bank (WB recommendations. A linear programming (LP model and goal linear programming model (GLP are adequate since price and nutrient contents are linearly related to food weight. The LP model provides information about the minimal value and the structure of the food basket for an average person in BiH based on nutrient needs. GLP models are designed to give us information on minimal deviations from nutrient needs if the budget is fixed. Based on these results, poverty analysis can be performed. The data used for the models consisted of 158 food items from the general consumption of the population of BiH according to COICOP classifications, with average prices in 2015 for these products.

  9. Linear VSS and Distributed Commitments Based on Secret Sharing and Pairwise Checks

    DEFF Research Database (Denmark)

    Fehr, Serge; Maurer, Ueli M.

    2002-01-01

    . VSS and DC are main building blocks for unconditional secure multi-party computation protocols. This general approach covers all known linear VSS and DC schemes. The main theorem states that the security of a scheme is equivalent to a pure linear-algebra condition on the linear mappings (e.......g. described as matrices and vectors) describing the scheme. The security of all known schemes follows as corollaries whose proofs are pure linear-algebra arguments, in contrast to some hybrid arguments used in the literature. Our approach is demonstrated for the CDM DC scheme, which we generalize to be secure...

  10. Emphasizing Language and Visualization in Teaching Linear Algebra

    Science.gov (United States)

    Hannah, John; Stewart, Sepideh; Thomas, Mike

    2013-01-01

    Linear algebra with its rich theoretical nature is a first step towards advanced mathematical thinking for many undergraduate students. In this paper, we consider the teaching approach of an experienced mathematician as he attempts to engage his students with the key ideas embedded in a second-year course in linear algebra. We describe his…

  11. The simplex method of linear programming

    CERN Document Server

    Ficken, Frederick A

    1961-01-01

    This concise but detailed and thorough treatment discusses the rudiments of the well-known simplex method for solving optimization problems in linear programming. Geared toward undergraduate students, the approach offers sufficient material for readers without a strong background in linear algebra. Many different kinds of problems further enrich the presentation. The text begins with examinations of the allocation problem, matrix notation for dual problems, feasibility, and theorems on duality and existence. Subsequent chapters address convex sets and boundedness, the prepared problem and boun

  12. Efficient Implementation of Solvers for Linear Model Predictive Control on Embedded Devices

    DEFF Research Database (Denmark)

    Frison, Gianluca; Kwame Minde Kufoalor, D.; Imsland, Lars

    2014-01-01

    This paper proposes a novel approach for the efficient implementation of solvers for linear MPC on embedded devices. The main focus is to explain in detail the approach used to optimize the linear algebra for selected low-power embedded devices, and to show how the high-performance implementation...

  13. Plane answers to complex questions the theory of linear models

    CERN Document Server

    Christensen, Ronald

    1987-01-01

    This book was written to rigorously illustrate the practical application of the projective approach to linear models. To some, this may seem contradictory. I contend that it is possible to be both rigorous and illustrative and that it is possible to use the projective approach in practical applications. Therefore, unlike many other books on linear models, the use of projections and sub­ spaces does not stop after the general theory. They are used wherever I could figure out how to do it. Solving normal equations and using calculus (outside of maximum likelihood theory) are anathema to me. This is because I do not believe that they contribute to the understanding of linear models. I have similar feelings about the use of side conditions. Such topics are mentioned when appropriate and thenceforward avoided like the plague. On the other side of the coin, I just as strenuously reject teaching linear models with a coordinate free approach. Although Joe Eaton assures me that the issues in complicated problems freq...

  14. An Optimal Linear Coding for Index Coding Problem

    OpenAIRE

    Pezeshkpour, Pouya

    2015-01-01

    An optimal linear coding solution for index coding problem is established. Instead of network coding approach by focus on graph theoric and algebraic methods a linear coding program for solving both unicast and groupcast index coding problem is presented. The coding is proved to be the optimal solution from the linear perspective and can be easily utilize for any number of messages. The importance of this work is lying mostly on the usage of the presented coding in the groupcast index coding ...

  15. Comparing linear probability model coefficients across groups

    DEFF Research Database (Denmark)

    Holm, Anders; Ejrnæs, Mette; Karlson, Kristian Bernt

    2015-01-01

    of the following three components: outcome truncation, scale parameters and distributional shape of the predictor variable. These results point to limitations in using linear probability model coefficients for group comparisons. We also provide Monte Carlo simulations and real examples to illustrate......This article offers a formal identification analysis of the problem in comparing coefficients from linear probability models between groups. We show that differences in coefficients from these models can result not only from genuine differences in effects, but also from differences in one or more...... these limitations, and we suggest a restricted approach to using linear probability model coefficients in group comparisons....

  16. Towards linearization of atmospheric radiative transfer in spherical geometry

    International Nuclear Information System (INIS)

    Walter, Holger H.; Landgraf, Jochen

    2005-01-01

    We present a general approach for the linearization of radiative transfer in a spherical planetary atmosphere. The approach is based on the forward-adjoint perturbation theory. In the first part we develop the theoretical background for a linearization of radiative transfer in spherical geometry. Using an operator formulation of radiative transfer allows one to derive the linearization principles in a universally valid notation. The application of the derived principles is demonstrated for a radiative transfer problem in simplified spherical geometry in the second part of this paper. Here, we calculate the derivatives of the radiance at the top of the atmosphere with respect to the absorption properties of a trace gas species in the case of a nadir-viewing satellite instrument

  17. Linear and non-linear interdependence of EEG and HRV frequency bands in human sleep.

    Science.gov (United States)

    Chaparro-Vargas, Ramiro; Dissanayaka, P Chamila; Patti, Chanakya Reddy; Schilling, Claudia; Schredl, Michael; Cvetkovic, Dean

    2014-01-01

    The characterisation of functional interdependencies of the autonomic nervous system (ANS) stands an evergrowing interest to unveil electroencephalographic (EEG) and Heart Rate Variability (HRV) interactions. This paper presents a biosignal processing approach as a supportive computational resource in the estimation of sleep dynamics. The application of linear, non-linear methods and statistical tests upon 10 overnight polysomnographic (PSG) recordings, allowed the computation of wavelet coherence and phase locking values, in order to identify discerning features amongst the clinical healthy subjects. Our findings showed that neuronal oscillations θ, α and σ interact with cardiac power bands at mid-to-high rank of coherence and phase locking, particularly during NREM sleep stages.

  18. Parameter Estimation of Partial Differential Equation Models

    KAUST Repository

    Xun, Xiaolei

    2013-09-01

    Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown and need to be estimated from the measurements of the dynamic system in the presence of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from long-range infrared light detection and ranging data. Supplementary materials for this article are available online. © 2013 American Statistical Association.

  19. Adaptive Algebraic Multigrid for Finite Element Elliptic Equations with Random Coefficients

    Energy Technology Data Exchange (ETDEWEB)

    Kalchev, D

    2012-04-02

    This thesis presents a two-grid algorithm based on Smoothed Aggregation Spectral Element Agglomeration Algebraic Multigrid (SA-{rho}AMGe) combined with adaptation. The aim is to build an efficient solver for the linear systems arising from discretization of second-order elliptic partial differential equations (PDEs) with stochastic coefficients. Examples include PDEs that model subsurface flow with random permeability field. During a Markov Chain Monte Carlo (MCMC) simulation process, that draws PDE coefficient samples from a certain distribution, the PDE coefficients change, hence the resulting linear systems to be solved change. At every such step the system (discretized PDE) needs to be solved and the computed solution used to evaluate some functional(s) of interest that then determine if the coefficient sample is acceptable or not. The MCMC process is hence computationally intensive and requires the solvers used to be efficient and fast. This fact that at every step of MCMC the resulting linear system changes, makes an already existing solver built for the old problem perhaps not as efficient for the problem corresponding to the new sampled coefficient. This motivates the main goal of our study, namely, to adapt an already existing solver to handle the problem (with changed coefficient) with the objective to achieve this goal to be faster and more efficient than building a completely new solver from scratch. Our approach utilizes the local element matrices (for the problem with changed coefficients) to build local problems associated with constructed by the method agglomerated elements (a set of subdomains that cover the given computational domain). We solve a generalized eigenproblem for each set in a subspace spanned by the previous local coarse space (used for the old solver) and a vector, component of the error, that the old solver cannot handle. A portion of the spectrum of these local eigen-problems (corresponding to eigenvalues close to zero) form the

  20. Stability test for a parabolic partial differential equation

    NARCIS (Netherlands)

    Vajta, Miklos

    2001-01-01

    The paper describes a stability test applied to coupled parabolic partial differential equations. The PDE's describe the temperature distribution of composite structures with linear inner heat sources. The distributed transfer functions are developed based on the transmission matrix of each layer.

  1. Joint shape segmentation with linear programming

    KAUST Repository

    Huang, Qixing; Koltun, Vladlen; Guibas, Leonidas

    2011-01-01

    program is solved via a linear programming relaxation, using a block coordinate descent procedure that makes the optimization feasible for large databases. We evaluate the presented approach on the Princeton segmentation benchmark and show that joint shape

  2. Portfolio optimization by using linear programing models based on genetic algorithm

    Science.gov (United States)

    Sukono; Hidayat, Y.; Lesmana, E.; Putra, A. S.; Napitupulu, H.; Supian, S.

    2018-01-01

    In this paper, we discussed the investment portfolio optimization using linear programming model based on genetic algorithms. It is assumed that the portfolio risk is measured by absolute standard deviation, and each investor has a risk tolerance on the investment portfolio. To complete the investment portfolio optimization problem, the issue is arranged into a linear programming model. Furthermore, determination of the optimum solution for linear programming is done by using a genetic algorithm. As a numerical illustration, we analyze some of the stocks traded on the capital market in Indonesia. Based on the analysis, it is shown that the portfolio optimization performed by genetic algorithm approach produces more optimal efficient portfolio, compared to the portfolio optimization performed by a linear programming algorithm approach. Therefore, genetic algorithms can be considered as an alternative on determining the investment portfolio optimization, particularly using linear programming models.

  3. Linear Equating for the NEAT Design: Parameter Substitution Models and Chained Linear Relationship Models

    Science.gov (United States)

    Kane, Michael T.; Mroch, Andrew A.; Suh, Youngsuk; Ripkey, Douglas R.

    2009-01-01

    This paper analyzes five linear equating models for the "nonequivalent groups with anchor test" (NEAT) design with internal anchors (i.e., the anchor test is part of the full test). The analysis employs a two-dimensional framework. The first dimension contrasts two general approaches to developing the equating relationship. Under a "parameter…

  4. Linear accelerators of the future

    International Nuclear Information System (INIS)

    Loew, G.A.

    1986-07-01

    Some of the requirements imposed on future linear accelerators to be used in electron-positron colliders are reviewed, as well as some approaches presently being examined for meeting those requirements. RF sources for use in these linacs are described, as well as wakefields, single bunches, and multiple-bunch trains

  5. Straight line fitting and predictions: On a marginal likelihood approach to linear regression and errors-in-variables models

    Science.gov (United States)

    Christiansen, Bo

    2015-04-01

    Linear regression methods are without doubt the most used approaches to describe and predict data in the physical sciences. They are often good first order approximations and they are in general easier to apply and interpret than more advanced methods. However, even the properties of univariate regression can lead to debate over the appropriateness of various models as witnessed by the recent discussion about climate reconstruction methods. Before linear regression is applied important choices have to be made regarding the origins of the noise terms and regarding which of the two variables under consideration that should be treated as the independent variable. These decisions are often not easy to make but they may have a considerable impact on the results. We seek to give a unified probabilistic - Bayesian with flat priors - treatment of univariate linear regression and prediction by taking, as starting point, the general errors-in-variables model (Christiansen, J. Clim., 27, 2014-2031, 2014). Other versions of linear regression can be obtained as limits of this model. We derive the likelihood of the model parameters and predictands of the general errors-in-variables model by marginalizing over the nuisance parameters. The resulting likelihood is relatively simple and easy to analyze and calculate. The well known unidentifiability of the errors-in-variables model is manifested as the absence of a well-defined maximum in the likelihood. However, this does not mean that probabilistic inference can not be made; the marginal likelihoods of model parameters and the predictands have, in general, well-defined maxima. We also include a probabilistic version of classical calibration and show how it is related to the errors-in-variables model. The results are illustrated by an example from the coupling between the lower stratosphere and the troposphere in the Northern Hemisphere winter.

  6. Widely Linear Equalization for IQ Imbalance and Skew Compensation in Optical Coherent Receivers

    DEFF Research Database (Denmark)

    Porto da Silva, Edson; Zibar, Darko

    2016-01-01

    In this paper, an alternative approach to design linear equalization algorithms for optical coherent receivers is introduced. Using widely linear complex analysis, a general analytical model it is shown, where In-phase/quadrature (IQ) imbalances and IQ skew at the coherent receiver front-end are ......In this paper, an alternative approach to design linear equalization algorithms for optical coherent receivers is introduced. Using widely linear complex analysis, a general analytical model it is shown, where In-phase/quadrature (IQ) imbalances and IQ skew at the coherent receiver front...

  7. The intelligence of dual simplex method to solve linear fractional fuzzy transportation problem.

    Science.gov (United States)

    Narayanamoorthy, S; Kalyani, S

    2015-01-01

    An approach is presented to solve a fuzzy transportation problem with linear fractional fuzzy objective function. In this proposed approach the fractional fuzzy transportation problem is decomposed into two linear fuzzy transportation problems. The optimal solution of the two linear fuzzy transportations is solved by dual simplex method and the optimal solution of the fractional fuzzy transportation problem is obtained. The proposed method is explained in detail with an example.

  8. Electronic excitation of the b 3Σ+sub(u) state of H2 by electron impact in the linear algebraic approach

    International Nuclear Information System (INIS)

    Schneider, B.I.; Collins, L.A.

    1985-01-01

    Two-state close-coupling calculations have been performed on the X 1 Σsub(g) to b 3 Σsub(u) transition for e-H 2 scattering within the linear algebraic, effective optical potential approach. The strong orthogonality constraint between bound and continuum orbitals is relaxed by including correlation-type configurations. These correlation terms prove to be very important in the 2 Σsub(g) and 2 Σsub(u) symmetries and lead to an increase in the total cross section of a factor of two over earlier approaches, which neglected these terms. Good agreement is obtained with recent R-matrix and Schwinger variational calculations. (author)

  9. Frequency-domain full-waveform inversion with non-linear descent directions

    Science.gov (United States)

    Geng, Yu; Pan, Wenyong; Innanen, Kristopher A.

    2018-05-01

    Full-waveform inversion (FWI) is a highly non-linear inverse problem, normally solved iteratively, with each iteration involving an update constructed through linear operations on the residuals. Incorporating a flexible degree of non-linearity within each update may have important consequences for convergence rates, determination of low model wavenumbers and discrimination of parameters. We examine one approach for doing so, wherein higher order scattering terms are included within the sensitivity kernel during the construction of the descent direction, adjusting it away from that of the standard Gauss-Newton approach. These scattering terms are naturally admitted when we construct the sensitivity kernel by varying not the current but the to-be-updated model at each iteration. Linear and/or non-linear inverse scattering methodologies allow these additional sensitivity contributions to be computed from the current data residuals within any given update. We show that in the presence of pre-critical reflection data, the error in a second-order non-linear update to a background of s0 is, in our scheme, proportional to at most (Δs/s0)3 in the actual parameter jump Δs causing the reflection. In contrast, the error in a standard Gauss-Newton FWI update is proportional to (Δs/s0)2. For numerical implementation of more complex cases, we introduce a non-linear frequency-domain scheme, with an inner and an outer loop. A perturbation is determined from the data residuals within the inner loop, and a descent direction based on the resulting non-linear sensitivity kernel is computed in the outer loop. We examine the response of this non-linear FWI using acoustic single-parameter synthetics derived from the Marmousi model. The inverted results vary depending on data frequency ranges and initial models, but we conclude that the non-linear FWI has the capability to generate high-resolution model estimates in both shallow and deep regions, and to converge rapidly, relative to a

  10. A Thermodynamic Theory Of Solid Viscoelasticity. Part 1: Linear Viscoelasticity.

    Science.gov (United States)

    Freed, Alan D.; Leonov, Arkady I.

    2002-01-01

    The present series of three consecutive papers develops a general theory for linear and finite solid viscoelasticity. Because the most important object for nonlinear studies are rubber-like materials, the general approach is specified in a form convenient for solving problems important for many industries that involve rubber-like materials. General linear and nonlinear theories for non-isothermal deformations of viscoelastic solids are developed based on the quasi-linear approach of non-equilibrium thermodynamics. In this, the first paper of the series, we analyze non-isothermal linear viscoelasticity, which is applicable in a range of small strains not only to all synthetic polymers and bio-polymers but also to some non-polymeric materials. Although the linear case seems to be well developed, there still are some reasons to implement a thermodynamic derivation of constitutive equations for solid-like, non-isothermal, linear viscoelasticity. The most important is the thermodynamic modeling of thermo-rheological complexity , i.e. different temperature dependences of relaxation parameters in various parts of relaxation spectrum. A special structure of interaction matrices is established for different physical mechanisms contributed to the normal relaxation modes. This structure seems to be in accord with observations, and creates a simple mathematical framework for both continuum and molecular theories of the thermo-rheological complex relaxation phenomena. Finally, a unified approach is briefly discussed that, in principle, allows combining both the long time (discrete) and short time (continuous) descriptions of relaxation behaviors for polymers in the rubbery and glassy regions.

  11. Linear Algebra and Smarandache Linear Algebra

    OpenAIRE

    Vasantha, Kandasamy

    2003-01-01

    The present book, on Smarandache linear algebra, not only studies the Smarandache analogues of linear algebra and its applications, it also aims to bridge the need for new research topics pertaining to linear algebra, purely in the algebraic sense. We have introduced Smarandache semilinear algebra, Smarandache bilinear algebra and Smarandache anti-linear algebra and their fuzzy equivalents. Moreover, in this book, we have brought out the study of linear algebra and vector spaces over finite p...

  12. Coarse-graining free theories with gauge symmetries: the linearized case

    International Nuclear Information System (INIS)

    Bahr, Benjamin; Dittrich, Bianca; He Song

    2011-01-01

    Discretizations of continuum theories often do not preserve the gauge symmetry content. This occurs in particular for diffeomorphism symmetry in general relativity, which leads to severe difficulties in both canonical and covariant quantization approaches. We discuss here the method of perfect actions, which attempts to restore gauge symmetries by mirroring exactly continuum physics on a lattice via a coarse graining process. Analytical results can only be obtained via a perturbative approach, for which we consider the first step, namely the coarse graining of the linearized theory. The linearized gauge symmetries are exact also in the discretized theory; hence, we develop a formalism to deal with gauge systems. Finally, we provide a discretization of linearized gravity as well as a coarse graining map and show that with this choice the three-dimensional (3D) linearized gravity action is invariant under coarse graining.

  13. A new approach of binary addition and subtraction by non-linear ...

    Indian Academy of Sciences (India)

    optical domain by exploitation of proper non-linear material-based switching technique. In this communication, the authors extend this technique for both adder and subtractor accommodating the spatial input encoding system.

  14. On the discretization of linear fractional representations of LPV systems

    NARCIS (Netherlands)

    Toth, R.; Lovera, M.; Heuberger, P.S.C.; Corno, M.; Hof, Van den P.M.J.

    2012-01-01

    Commonly, controllers for linear parameter-varying (LPV) systems are designed in continuous time using a linear fractional representation (LFR) of the plant. However, the resulting controllers are implemented on digital hardware. Furthermore, discrete-time LPV synthesis approaches require a

  15. A Practical Approach to Inquiry-Based Learning in Linear Algebra

    Science.gov (United States)

    Chang, J.-M.

    2011-01-01

    Linear algebra has become one of the most useful fields of mathematics since last decade, yet students still have trouble seeing the connection between some of the abstract concepts and real-world applications. In this article, we propose the use of thought-provoking questions in lesson designs to allow two-way communications between instructors…

  16. Wavelet-linear genetic programming: A new approach for modeling monthly streamflow

    Science.gov (United States)

    Ravansalar, Masoud; Rajaee, Taher; Kisi, Ozgur

    2017-06-01

    The streamflows are important and effective factors in stream ecosystems and its accurate prediction is an essential and important issue in water resources and environmental engineering systems. A hybrid wavelet-linear genetic programming (WLGP) model, which includes a discrete wavelet transform (DWT) and a linear genetic programming (LGP) to predict the monthly streamflow (Q) in two gauging stations, Pataveh and Shahmokhtar, on the Beshar River at the Yasuj, Iran were used in this study. In the proposed WLGP model, the wavelet analysis was linked to the LGP model where the original time series of streamflow were decomposed into the sub-time series comprising wavelet coefficients. The results were compared with the single LGP, artificial neural network (ANN), a hybrid wavelet-ANN (WANN) and Multi Linear Regression (MLR) models. The comparisons were done by some of the commonly utilized relevant physical statistics. The Nash coefficients (E) were found as 0.877 and 0.817 for the WLGP model, for the Pataveh and Shahmokhtar stations, respectively. The comparison of the results showed that the WLGP model could significantly increase the streamflow prediction accuracy in both stations. Since, the results demonstrate a closer approximation of the peak streamflow values by the WLGP model, this model could be utilized for the simulation of cumulative streamflow data prediction in one month ahead.

  17. The Intelligence of Dual Simplex Method to Solve Linear Fractional Fuzzy Transportation Problem

    Directory of Open Access Journals (Sweden)

    S. Narayanamoorthy

    2015-01-01

    Full Text Available An approach is presented to solve a fuzzy transportation problem with linear fractional fuzzy objective function. In this proposed approach the fractional fuzzy transportation problem is decomposed into two linear fuzzy transportation problems. The optimal solution of the two linear fuzzy transportations is solved by dual simplex method and the optimal solution of the fractional fuzzy transportation problem is obtained. The proposed method is explained in detail with an example.

  18. Phosphodiesterase inhibitors in clinical urology.

    Science.gov (United States)

    Ückert, Stefan; Kuczyk, Markus A; Oelke, Matthias

    2013-05-01

    To date, benign diseases of the male and female lower urinary and genital tract, such as erectile dysfunction, bladder overactivity, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and symptoms of female sexual dysfunction (including arousal and orgasmic disorders), can be therapeutically approached by influencing the function of the smooth musculature of the respective tissues. The use of isoenzyme-selective phosphodiesterase (PDE) inhibitors is considered a great opportunity to treat various diseases of the human urogenital tract. PDE inhibitors, in particular the PDE5 (cyclic GMP PDE) inhibitors avanafil, lodenafil, sildenafil, tadalafil, udenafil and vardenafil, are regarded as efficacious, having a fast onset of drug action and an improved effect-to-adverse event ratio, combining a high response rate with the advantage of an on-demand intake. The purpose of this review is to summarize recent as well as potential future indications, namely, erectile dysfunction, Peyronie's disease, overactive bladder, urinary stone disease, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and premature ejaculation, for the use of PDE inhibitors in clinical urology.

  19. LINEAR AND NON-LINEAR ANALYSES OF CABLE-STAYED STEEL FRAME SUBJECTED TO SEISMIC ACTIONS

    Directory of Open Access Journals (Sweden)

    Marko Đuran

    2017-01-01

    Full Text Available In this study, linear and non-linear dynamic analyses of a cable-stayed steel frame subjected to seismic actions are performed. The analyzed cable-stayed frame is the main supporting structure of a wide-span sports hall. Since the complex dynamic behavior of cable-stayed structures results in significant geometric nonlinearity, a nonlinear time history analysis is conducted. As a reference, an analysis using the European standard approach, the so-called linear modal response spectrum method, is also performed. The analyses are conducted for different seismic actions considering dependence on the response spectrums for various ground types and the corresponding artificially generated accelerograms. Despite fundamental differences between the two analyses, results indicate that the modal response spectrum analysis is surprisingly consistent with the internal forces and bending moment distributions of the nonlinear time history analysis. However, significantly smaller values of bending moments, internal forces, and displacements are obtained with the response spectrum analysis.

  20. One-Photon Absorption Properties from a Hybrid Polarizable Density Embedding/Complex Polarization Propagator Approach for Polarizable Solutions

    DEFF Research Database (Denmark)

    Hršak, Dalibor; Nørby, Morten Steen; Coriani, Sonia

    2018-01-01

    We present a formulation of the polarizable density embedding (PDE) method in combination with the complex polarization propagator (CPP) method for the calculation of absorption spectra of molecules in solutions. The method is particularly useful for the calculation of near-edge X-ray absorption...... fine structure (NEXAFS) spectra. We compare the performance of PDE-CPP with the previously formulated polarizable embedding (PE)-CPP model for the calculation of the NEXAFS spectra of adenine, formamide, glycine, and adenosine triphosphate (ATP) in water at the carbon and nitrogen K-edges, as well...