Small-kernel, constrained least-squares restoration of sampled image data

NASA Technical Reports Server (NTRS)

Hazra, Rajeeb; Park, Stephen K.

1992-01-01

Following the work of Park (1989), who extended a derivation of the Wiener filter based on the incomplete discrete/discrete model to a more comprehensive end-to-end continuous/discrete/continuous model, it is shown that a derivation of the constrained least-squares (CLS) filter based on the discrete/discrete model can also be extended to this more comprehensive continuous/discrete/continuous model. This results in an improved CLS restoration filter, which can be efficiently implemented as a small-kernel convolution in the spatial domain.

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

PubMed

Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

2014-01-01

Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

Extended causal modeling to assess Partial Directed Coherence in multiple time series with significant instantaneous interactions.

PubMed

Faes, Luca; Nollo, Giandomenico

2010-11-01

The Partial Directed Coherence (PDC) and its generalized formulation (gPDC) are popular tools for investigating, in the frequency domain, the concept of Granger causality among multivariate (MV) time series. PDC and gPDC are formalized in terms of the coefficients of an MV autoregressive (MVAR) model which describes only the lagged effects among the time series and forsakes instantaneous effects. However, instantaneous effects are known to affect linear parametric modeling, and are likely to occur in experimental time series. In this study, we investigate the impact on the assessment of frequency domain causality of excluding instantaneous effects from the model underlying PDC evaluation. Moreover, we propose the utilization of an extended MVAR model including both instantaneous and lagged effects. This model is used to assess PDC either in accordance with the definition of Granger causality when considering only lagged effects (iPDC), or with an extended form of causality, when we consider both instantaneous and lagged effects (ePDC). The approach is first evaluated on three theoretical examples of MVAR processes, which show that the presence of instantaneous correlations may produce misleading profiles of PDC and gPDC, while ePDC and iPDC derived from the extended model provide here a correct interpretation of extended and lagged causality. It is then applied to representative examples of cardiorespiratory and EEG MV time series. They suggest that ePDC and iPDC are better interpretable than PDC and gPDC in terms of the known cardiovascular and neural physiologies.

Computation of forces arising from the polarizable continuum model within the domain-decomposition paradigm

NASA Astrophysics Data System (ADS)

Gatto, Paolo; Lipparini, Filippo; Stamm, Benjamin

2017-12-01

The domain-decomposition (dd) paradigm, originally introduced for the conductor-like screening model, has been recently extended to the dielectric Polarizable Continuum Model (PCM), resulting in the ddPCM method. We present here a complete derivation of the analytical derivatives of the ddPCM energy with respect to the positions of the solute's atoms and discuss their efficient implementation. As it is the case for the energy, we observe a quadratic scaling, which is discussed and demonstrated with numerical tests.

Kinematics of reflections in subsurface offset and angle-domain image gathers

NASA Astrophysics Data System (ADS)

Dafni, Raanan; Symes, William W.

2018-05-01

Seismic migration in the angle-domain generates multiple images of the earth's interior in which reflection takes place at different scattering-angles. Mechanically, the angle-dependent reflection is restricted to happen instantaneously and at a fixed point in space: Incident wave hits a discontinuity in the subsurface media and instantly generates a scattered wave at the same common point of interaction. Alternatively, the angle-domain image may be associated with space-shift (regarded as subsurface offset) extended migration that artificially splits the reflection geometry. Meaning that, incident and scattered waves interact at some offset distance. The geometric differences between the two approaches amount to a contradictory angle-domain behaviour, and unlike kinematic description. We present a phase space depiction of migration methods extended by the peculiar subsurface offset split and stress its profound dissimilarity. In spite of being in radical contradiction with the general physics, the subsurface offset reveals a link to some valuable angle-domain quantities, via post-migration transformations. The angle quantities are indicated by the direction normal to the subsurface offset extended image. They specifically define the local dip and scattering angles if the velocity at the split reflection coordinates is the same for incident and scattered wave pairs. Otherwise, the reflector normal is not a bisector of the opening angle, but of the corresponding slowness vectors. This evidence, together with the distinguished geometry configuration, fundamentally differentiates the angle-domain decomposition based on the subsurface offset split from the conventional decomposition at a common reflection point. An asymptotic simulation of angle-domain moveout curves in layered media exposes the notion of split versus common reflection point geometry. Traveltime inversion methods that involve the subsurface offset extended migration must accommodate the split geometry in the inversion scheme for a robust and successful convergence at the optimal velocity model.

Frequency domain, waveform inversion of laboratory crosswell radar data

USGS Publications Warehouse

Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

2010-01-01

A new waveform inversion for crosswell radar is formulated in the frequency-domain for a 2.5D model. The inversion simulates radar waves using the vector Helmholtz equation for electromagnetic waves. The objective function is minimized using a backpropagation method suitable for a 2.5D model. The inversion is tested by processing crosswell radar data collected in a laboratory tank. The estimated model is consistent with the known electromagnetic properties of the tank. The formulation for the 2.5D model can be extended to inversions of acoustic and elastic data.

A Review of System Identification Methods Applied to Aircraft

NASA Technical Reports Server (NTRS)

Klein, V.

1983-01-01

Airplane identification, equation error method, maximum likelihood method, parameter estimation in frequency domain, extended Kalman filter, aircraft equations of motion, aerodynamic model equations, criteria for the selection of a parsimonious model, and online aircraft identification are addressed.

Extended Kalman filtering for the detection of damage in linear mechanical structures

NASA Astrophysics Data System (ADS)

Liu, X.; Escamilla-Ambrosio, P. J.; Lieven, N. A. J.

2009-09-01

This paper addresses the problem of assessing the location and extent of damage in a vibrating structure by means of vibration measurements. Frequency domain identification methods (e.g. finite element model updating) have been widely used in this area while time domain methods such as the extended Kalman filter (EKF) method, are more sparsely represented. The difficulty of applying EKF in mechanical system damage identification and localisation lies in: the high computational cost, the dependence of estimation results on the initial estimation error covariance matrix P(0), the initial value of parameters to be estimated, and on the statistics of measurement noise R and process noise Q. To resolve these problems in the EKF, a multiple model adaptive estimator consisting of a bank of EKF in modal domain was designed, each filter in the bank is based on different P(0). The algorithm was iterated by using the weighted global iteration method. A fuzzy logic model was incorporated in each filter to estimate the variance of the measurement noise R. The application of the method is illustrated by simulated and real examples.

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong

2014-01-01

Objectives Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Methods Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. Results In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. Conclusions A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models. PMID:24627817

Decisons To Promote or Hire: The Case of University Administrative Appointments. ASHE Annual Meeting Paper.

ERIC Educational Resources Information Center

Johnsrud, Linda K.; Sagaria, Mary Ann D.

Internal labor market theory is extended to identify market domains that influence administrative staffing decisions, and a theoretical predictive model about the role of market domains in decisions to promote or hire is proposed and tested. Information is presented as follows: theoretical framework; labor markets within higher education; and the…

Performance analysis of FET microwave devices by use of extended spectral-element time-domain method

NASA Astrophysics Data System (ADS)

Sheng, Yijun; Xu, Kan; Wang, Daoxiang; Chen, Rushan

2013-05-01

The extended spectral-element time-domain (SETD) method is employed to analyse field effect transistor (FET) microwave devices. In order to impose the contribution of the FET microwave devices into the electromagnetic simulation, the SETD method is extended by introducing a lumped current term into the vector Helmholtz equation. The change of currents on each lumped component can be expressed by the change of voltage via corresponding models of equivalent circuit. The electric fields around the lumped component must be influenced by the change of voltage on each lumped component, and vice versa. So a global coupling about the EM-circuit can be built directly. The fully explicit solving scheme is maintained in this extended SETD method and the CPU time can be saved spontaneously. Three practical FET microwave devices are analysed in this article. The numerical results demonstrate the ability and accuracy of this method.

Cerebellar contributions to motor control and language comprehension: searching for common computational principles.

PubMed

Moberget, Torgeir; Ivry, Richard B

2016-04-01

The past 25 years have seen the functional domain of the cerebellum extend beyond the realm of motor control, with considerable discussion of how this subcortical structure contributes to cognitive domains including attention, memory, and language. Drawing on evidence from neuroanatomy, physiology, neuropsychology, and computational work, sophisticated models have been developed to describe cerebellar function in sensorimotor control and learning. In contrast, mechanistic accounts of how the cerebellum contributes to cognition have remained elusive. Inspired by the homogeneous cerebellar microanatomy and a desire for parsimony, many researchers have sought to extend mechanistic ideas from motor control to cognition. One influential hypothesis centers on the idea that the cerebellum implements internal models, representations of the context-specific dynamics of an agent's interactions with the environment, enabling predictive control. We briefly review cerebellar anatomy and physiology, to review the internal model hypothesis as applied in the motor domain, before turning to extensions of these ideas in the linguistic domain, focusing on speech perception and semantic processing. While recent findings are consistent with this computational generalization, they also raise challenging questions regarding the nature of cerebellar learning, and may thus inspire revisions of our views on the role of the cerebellum in sensorimotor control. © 2016 New York Academy of Sciences.

AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

PubMed Central

Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

2015-01-01

Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

What are the Geophysical Fingerprints of hyper-extended Crustal Domains ?

NASA Astrophysics Data System (ADS)

Stanton, N.; Manatschal, G.; Maia, M.; Viana, A.; Tugend, J.; Autin, J.

2012-04-01

The Iberian margin is a well-studied region and presently the best tectonic setting for understanding the dynamic process of margin's formation and evolution. The world largest available dataset enabled to properly constrain the crustal structure and opened new paradigms for passive margins studies. Nevertheless, there are numerous remaining questions, as for example what is the spatial extent of continental inheritance along the margin and what is the role of fluids (serpentinization/magmatism) during margin's formation/deformation? The observation of a hyper-extended crustal domain, now also identified in other margins reveals the highly diverse nature of the crust along rifted margins. What are its physical properties and how do they change laterally? The aim of this study is to explore the physical signature of the serpentinized crust, which composes this hyper-extended domain, to identify the limits of the system and discuss its nature and importance. To investigate the lateral variation of crustal types we use integrated gravity, magnetic, seismic and available geological/well data. Transformations on the potential field data enable us to enhance the horizontal and vertical variations of the crust, and future forward modeling will provide a geological correlation for Iberia. The preliminary results showed that the transitional crust can be subdivided into two zones, regarding their different geophysical signatures: from the necking zone, the continent ward transitional crust displays decreasing gravity anomaly, low horizontal gradient and smooth magnetic anomalies; towards offshore (to the west of the J anomaly) the transitional crust is characterized by a semi-cyclic magnetic anomaly pattern, with increasing gravity, showing a stronger horizontal gradient and rough bathymetry. We associate this transitional domain with an embryonic oceanic type crust. Comparisons with other margins along the North Atlantic, despite the great spatial variation, reveals preliminarily that the hyper-extended crust at the non-volcanic Iberia Margin displays intrinsic characteristics distinct from the more volcanic transitional domains to the north. The physical properties of the different crustal types will be further modeled to properly constrain their characteristics. The final results shall enable us to identify the lateral transition between the different continental-transitional hydrated-oceanic crustal types and potentially would allow us to identify similar domains worldwide.

A binomial modeling approach for upscaling colloid transport under unfavorable conditions: Emergent prediction of extended tailing

NASA Astrophysics Data System (ADS)

Hilpert, Markus; Rasmuson, Anna; Johnson, William P.

2017-07-01

Colloid transport in saturated porous media is significantly influenced by colloidal interactions with grain surfaces. Near-surface fluid domain colloids experience relatively low fluid drag and relatively strong colloidal forces that slow their downgradient translation relative to colloids in bulk fluid. Near-surface fluid domain colloids may reenter into the bulk fluid via diffusion (nanoparticles) or expulsion at rear flow stagnation zones, they may immobilize (attach) via primary minimum interactions, or they may move along a grain-to-grain contact to the near-surface fluid domain of an adjacent grain. We introduce a simple model that accounts for all possible permutations of mass transfer within a dual pore and grain network. The primary phenomena thereby represented in the model are mass transfer of colloids between the bulk and near-surface fluid domains and immobilization. Colloid movement is described by a Markov chain, i.e., a sequence of trials in a 1-D network of unit cells, which contain a pore and a grain. Using combinatorial analysis, which utilizes the binomial coefficient, we derive the residence time distribution, i.e., an inventory of the discrete colloid travel times through the network and of their probabilities to occur. To parameterize the network model, we performed mechanistic pore-scale simulations in a single unit cell that determined the likelihoods and timescales associated with the above colloid mass transfer processes. We found that intergrain transport of colloids in the near-surface fluid domain can cause extended tailing, which has traditionally been attributed to hydrodynamic dispersion emanating from flow tortuosity of solute trajectories.

Rating knowledge sharing in cross-domain collaborative filtering.

PubMed

Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

2015-05-01

Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

Time-domain wavefield reconstruction inversion

NASA Astrophysics Data System (ADS)

Li, Zhen-Chun; Lin, Yu-Zhao; Zhang, Kai; Li, Yuan-Yuan; Yu, Zhen-Nan

2017-12-01

Wavefield reconstruction inversion (WRI) is an improved full waveform inversion theory that has been proposed in recent years. WRI method expands the searching space by introducing the wave equation into the objective function and reconstructing the wavefield to update model parameters, thereby improving the computing efficiency and mitigating the influence of the local minimum. However, frequency-domain WRI is difficult to apply to real seismic data because of the high computational memory demand and requirement of time-frequency transformation with additional computational costs. In this paper, wavefield reconstruction inversion theory is extended into the time domain, the augmented wave equation of WRI is derived in the time domain, and the model gradient is modified according to the numerical test with anomalies. The examples of synthetic data illustrate the accuracy of time-domain WRI and the low dependency of WRI on low-frequency information.

Large exchange-dominated domain wall velocities in antiferromagnetically coupled nanowires

NASA Astrophysics Data System (ADS)

Kuteifan, Majd; Lubarda, M. V.; Fu, S.; Chang, R.; Escobar, M. A.; Mangin, S.; Fullerton, E. E.; Lomakin, V.

2016-04-01

Magnetic nanowires supporting field- and current-driven domain wall motion are envisioned for methods of information storage and processing. A major obstacle for their practical use is the domain-wall velocity, which is traditionally limited for low fields and currents due to the Walker breakdown occurring when the driving component reaches a critical threshold value. We show through numerical and analytical modeling that the Walker breakdown limit can be extended or completely eliminated in antiferromagnetically coupled magnetic nanowires. These coupled nanowires allow for large domain-wall velocities driven by field and/or current as compared to conventional nanowires.

Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.

PubMed

Stone, Matthew B; Shelby, Sarah A; Núñez, Marcos F; Wisser, Kathleen; Veatch, Sarah L

2017-02-01

Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.

Adjacent-Categories Mokken Models for Rater-Mediated Assessments

ERIC Educational Resources Information Center

Wind, Stefanie A.

2017-01-01

Molenaar extended Mokken's original probabilistic-nonparametric scaling models for use with polytomous data. These polytomous extensions of Mokken's original scaling procedure have facilitated the use of Mokken scale analysis as an approach to exploring fundamental measurement properties across a variety of domains in which polytomous ratings are…

Going from microscopic to macroscopic on nonuniform growing domains.

PubMed

Yates, Christian A; Baker, Ruth E; Erban, Radek; Maini, Philip K

2012-08-01

Throughout development, chemical cues are employed to guide the functional specification of underlying tissues while the spatiotemporal distributions of such chemicals can be influenced by the growth of the tissue itself. These chemicals, termed morphogens, are often modeled using partial differential equations (PDEs). The connection between discrete stochastic and deterministic continuum models of particle migration on growing domains was elucidated by Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration of individual particles was modeled as an on-lattice position-jump process. We build on this work by incorporating a more physically reasonable description of domain growth. Instead of allowing underlying lattice elements to instantaneously double in size and divide, we allow incremental element growth and splitting upon reaching a predefined threshold size. Such a description of domain growth necessitates a nonuniform partition of the domain. We first demonstrate that an individual-based stochastic model for particle diffusion on such a nonuniform domain partition is equivalent to a PDE model of the same phenomenon on a nongrowing domain, providing the transition rates (which we derive) are chosen correctly and we partition the domain in the correct manner. We extend this analysis to the case where the domain is allowed to change in size, altering the transition rates as necessary. Through application of the master equation formalism we derive a PDE for particle density on this growing domain and corroborate our findings with numerical simulations.

An Empirical Human Controller Model for Preview Tracking Tasks.

PubMed

van der El, Kasper; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus Rene M; Mulder, Max

2016-11-01

Real-life tracking tasks often show preview information to the human controller about the future track to follow. The effect of preview on manual control behavior is still relatively unknown. This paper proposes a generic operator model for preview tracking, empirically derived from experimental measurements. Conditions included pursuit tracking, i.e., without preview information, and tracking with 1 s of preview. Controlled element dynamics varied between gain, single integrator, and double integrator. The model is derived in the frequency domain, after application of a black-box system identification method based on Fourier coefficients. Parameter estimates are obtained to assess the validity of the model in both the time domain and frequency domain. Measured behavior in all evaluated conditions can be captured with the commonly used quasi-linear operator model for compensatory tracking, extended with two viewpoints of the previewed target. The derived model provides new insights into how human operators use preview information in tracking tasks.

Entropy gives rise to topologically associating domains

PubMed Central

Vasquez, Paula A.; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G.; Bloom, Kerry

2016-01-01

We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

Nonlinear dielectric response and transient current: An effective potential for ferroelectric domain wall displacement

NASA Astrophysics Data System (ADS)

Placeres Jiménez, Rolando; Pedro Rino, José; Marino Gonçalves, André; Antonio Eiras, José

2013-09-01

Ferroelectric domain walls are modeled as rigid bodies moving under the action of a potential field in a dissipative medium. Assuming that the dielectric permittivity follows the dependence ɛ '∝1/(α+βE2), it obtained the exact expression for the effective potential. Simulations of polarization current correctly predict a power law. Such results could be valuable in the study of domain wall kinetic and ultrafast polarization processes. The model is extended to poled samples allowing the study of nonlinear dielectric permittivity under subswitching electric fields. Experimental nonlinear data from PZT 20/80 thin films and Fe+3 doped PZT 40/60 ceramic are reproduced.

Flexibility on storage-release based distributed hydrologic modeling with object-oriented approach

USDA-ARS?s Scientific Manuscript database

With the availability of advanced hydrologic data in the public domain such as remotely sensed and climate change scenario data, there is a need for a modeling framework that is capable of using these data to simulate and extend hydrologic processes with multidisciplinary approaches for sustainable ...

Lee-Yang Polynomials and Ground States of Spin Systems

NASA Astrophysics Data System (ADS)

Slawny, Joseph

2014-08-01

We obtain two kinds of results on the region in the space of the interactions of lattice systems where the Lee-Yang property holds (LY domain). First we show that the LY domain is related to interactions with exactly two ground states. Then we give a description of the full LY domain of an extended "plaquette model" analyzed by Lebowitz and Ruelle (Commun Math Phys 304:711-722, 2011). This allows us to prove a permanence property of the system, which we conjecture to hold in general.

Cognitive Ability, Academic Achievement and Academic Self-Concept: Extending the Internal/External Frame of Reference Model

ERIC Educational Resources Information Center

Chen, Ssu-Kuang; Hwang, Fang-Ming; Yeh, Yu-Chen; Lin, Sunny S. J.

2012-01-01

Background: Marsh's internal/external (I/E) frame of reference model depicts the relationship between achievement and self-concept in specific academic domains. Few efforts have been made to examine concurrent relationships among cognitive ability, achievement, and academic self-concept (ASC) within an I/E model framework. Aim: To simultaneously…

Three case studies of the GasNet model in discrete domains.

PubMed

Santos, C L; de Oliveira, P P; Husbands, P; Souza, C R

2001-06-01

A new neural network model - the GasNet - has been recently reported in the literature, which, in addition to the traditional electric type, point-to-point communication between units, also uses communication through a diffilsable chemical modulator. Here we assess the applicability of this model in three different scenarios, the XOR problem, a food gathering task for a simulated robot, and a docking task for a virtual spaceship. All of them represent discrete domains, a contrast with the one where the GasNet was originally introduced, which had an essentially continuous nature. These scenarios are well-known benchmark problems from the literature and, since they exhibit varying degrees of complexity, they impose distinct performance demands on the GasNet. The experiments were primarily intended to better understand the model, by extending the original problem domain where GasNet was introduced. The results reported point at some difficulties with the current GasNet model.

Modeling reactive transport processes in fractured rock using the time domain random walk approach within a dual-porosity framework

NASA Astrophysics Data System (ADS)

Roubinet, D.; Russian, A.; Dentz, M.; Gouze, P.

2017-12-01

Characterizing and modeling hydrodynamic reactive transport in fractured rock are critical challenges for various research fields and applications including environmental remediation, geological storage, and energy production. To this end, we consider a recently developed time domain random walk (TDRW) approach, which is adapted to reproduce anomalous transport behaviors and capture heterogeneous structural and physical properties. This method is also very well suited to optimize numerical simulations by memory-shared massive parallelization and provide numerical results at various scales. So far, the TDRW approach has been applied for modeling advective-diffusive transport with mass transfer between mobile and immobile regions and simple (theoretical) reactions in heterogeneous porous media represented as single continuum domains. We extend this approach to dual-continuum representations considering a highly permeable fracture network embedded into a poorly permeable rock matrix with heterogeneous geochemical reactions occurring in both geological structures. The resulting numerical model enables us to extend the range of the modeled heterogeneity scales with an accurate representation of solute transport processes and no assumption on the Fickianity of these processes. The proposed model is compared to existing particle-based methods that are usually used to model reactive transport in fractured rocks assuming a homogeneous surrounding matrix, and is used to evaluate the impact of the matrix heterogeneity on the apparent reaction rates for different 2D and 3D simple-to-complex fracture network configurations.

Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION)

PubMed Central

Haider, Mansoor A.; Guilak, Farshid

2009-01-01

Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain. PMID:19851478

Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION).

PubMed

Haider, Mansoor A; Guilak, Farshid

2007-06-15

Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain.

SIENA Customer Problem Statement and Requirements

DOE Office of Scientific and Technical Information (OSTI.GOV)

L. Sauer; R. Clay; C. Adams

2000-08-01

This document describes the problem domain and functional requirements of the SIENA framework. The software requirements and system architecture of SIENA are specified in separate documents (called SIENA Software Requirement Specification and SIENA Software Architecture, respectively). While currently this version of the document describes the problems and captures the requirements within the Analysis domain (concentrating on finite element models), it is our intention to subsequent y expand this document to describe problems and capture requirements from the Design and Manufacturing domains. In addition, SIENA is designed to be extendible to support and integrate elements from the other domains (see SIENAmore » Software Architecture document).« less

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

Rio, Daniel E.; Rawlings, Robert R.; Woltz, Lawrence A.; Gilman, Jodi; Hommer, Daniel W.

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. PMID:23840281

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

PubMed

Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

DOE PAGES

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake; ...

2017-03-24

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

A Lattice Boltzmann Fictitious Domain Method for Modeling Red Blood Cell Deformation and Multiple-Cell Hydrodynamic Interactions in Flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xing; Lin, Guang; Zou, Jianfeng

To model red blood cell (RBC) deformation in flow, the recently developed LBM-DLM/FD method ([Shi and Lim, 2007)29], derived from the lattice Boltzmann method and the distributed Lagrange multiplier/fictitious domain methodthe fictitious domain method, is extended to employ the mesoscopic network model for simulations of red blood cell deformation. The flow is simulated by the lattice Boltzmann method with an external force, while the network model is used for modeling red blood cell deformation and the fluid-RBC interaction is enforced by the Lagrange multiplier. To validate parameters of the RBC network model, sThe stretching numerical tests on both coarse andmore » fine meshes are performed and compared with the corresponding experimental data to validate the parameters of the RBC network model. In addition, RBC deformation in pipe flow and in shear flow is simulated, revealing the capacity of the current method for modeling RBC deformation in various flows.« less

Domain walls in the extensions of the Standard Model

NASA Astrophysics Data System (ADS)

Krajewski, Tomasz; Lalak, Zygmunt; Lewicki, Marek; Olszewski, Paweł

2018-05-01

Our main interest is the evolution of domain walls of the Higgs field in the early Universe. The aim of this paper is to understand how dynamics of Higgs domain walls could be influenced by yet unknown interactions from beyond the Standard Model. We assume that the Standard Model is valid up to certain, high, energy scale Λ and use the framework of the effective field theory to describe physics below that scale. Performing numerical simulations with different values of the scale Λ we are able to extend our previous analysis [1]. Our recent numerical simulations show that evolution of Higgs domain walls is rather insensitive to interactions beyond the Standard Model as long as masses of new particles are grater than 1012 GeV. For lower values of Λ the RG improved effective potential is strongly modified at field strengths crucial to the evolution of domain walls. However, we find that even for low values of Λ, Higgs domain walls decayed shortly after their formation for generic initial conditions. On the other hand, in simulations with specifically chosen initial conditions Higgs domain walls can live longer and enter the scaling regime. We also determine the energy spectrum of gravitational waves produced by decaying domain walls of the Higgs field. For generic initial field configurations the amplitude of the signal is too small to be observed in planned detectors.

Goal-Based Domain Modeling as a Basis for Cross-Disciplinary Systems Engineering

NASA Astrophysics Data System (ADS)

Jarke, Matthias; Nissen, Hans W.; Rose, Thomas; Schmitz, Dominik

Small and medium-sized enterprises (SMEs) are important drivers for innovation. In particular, project-driven SMEs that closely cooperate with their customers have specific needs in regard to information engineering of their development process. They need a fast requirements capture since this is most often included in the (unpaid) offer development phase. At the same time, they need to maintain and reuse the knowledge and experiences they have gathered in previous projects extensively as it is their core asset. The situation is complicated further if the application field crosses disciplinary boundaries. To bridge the gaps and perspectives, we focus on shared goals and dependencies captured in models at a conceptual level. Such a model-based approach also offers a smarter connection to subsequent development stages, including a high share of automated code generation. In the approach presented here, the agent- and goal-oriented formalism i * is therefore extended by domain models to facilitate information organization. This extension permits a domain model-based similarity search, and a model-based transformation towards subsequent development stages. Our approach also addresses the evolution of domain models reflecting the experiences from completed projects. The approach is illustrated with a case study on software-intensive control systems in an SME of the automotive domain.

Structural Interface Forms and Their Involvement in Stabilization of Multidomain Proteins or Protein Complexes.

PubMed

Dygut, Jacek; Kalinowska, Barbara; Banach, Mateusz; Piwowar, Monika; Konieczny, Leszek; Roterman, Irena

2016-10-18

The presented analysis concerns the inter-domain and inter-protein interface in protein complexes. We propose extending the traditional understanding of the protein domain as a function of local compactness with an additional criterion which refers to the presence of a well-defined hydrophobic core. Interface areas in selected homodimers vary with respect to their contribution to share as well as individual (domain-specific) hydrophobic cores. The basic definition of a protein domain, i.e., a structural unit characterized by tighter packing than its immediate environment, is extended in order to acknowledge the role of a structured hydrophobic core, which includes the interface area. The hydrophobic properties of interfaces vary depending on the status of interacting domains-In this context we can distinguish: (1) Shared hydrophobic cores (spanning the whole dimer); (2) Individual hydrophobic cores present in each monomer irrespective of whether the dimer contains a shared core. Analysis of interfaces in dystrophin and utrophin indicates the presence of an additional quasi-domain with a prominent hydrophobic core, consisting of fragments contributed by both monomers. In addition, we have also attempted to determine the relationship between the type of interface (as categorized above) and the biological function of each complex. This analysis is entirely based on the fuzzy oil drop model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rushton, Phillip S.; Olek, Anna T.; Makowski, Lee

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 Å resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecularmore » envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery.« less

Discrete and continuous models for tissue growth and shrinkage.

PubMed

Yates, Christian A

2014-06-07

The incorporation of domain growth into stochastic models of biological processes is of increasing interest to mathematical modellers and biologists alike. In many situations, especially in developmental biology, the growth of the underlying tissue domain plays an important role in the redistribution of particles (be they cells or molecules) which may move and react atop the domain. Although such processes have largely been modelled using deterministic, continuum models there is an increasing appetite for individual-based stochastic models which can capture the fine details of the biological movement processes which are being elucidated by modern experimental techniques, and also incorporate the inherent stochasticity of such systems. In this work we study a simple stochastic model of domain growth. From a basic version of this model, Hywood et al. (2013) were able to derive a Fokker-Plank equation (FPE) (in this case an advection-diffusion partial differential equation on a growing domain) which describes the evolution of the probability density of some tracer particles on the domain. We extend their work so that a variety of different domain growth mechanisms can be incorporated and demonstrate a good agreement between the mean tracer density and the solution of the FPE in each case. In addition we incorporate domain shrinkage (via element death) into our individual-level model and demonstrate that we are able to derive coefficients for the FPE in this case as well. For situations in which the drift and diffusion coefficients are not readily available we introduce a numerical coefficient estimation approach and demonstrate the accuracy of this approach by comparing it with situations in which an analytical solution is obtainable. Copyright © 2014 Elsevier Ltd. All rights reserved.

Moving Beyond Conventional Wisdom: Advancements in Cross-Cultural Theories of Leadership, Conflict, and Teams.

PubMed

Gibson, Cristina B; McDaniel, Dana M

2010-07-01

In this article, we discuss the importance of a cross-cultural approach to organizational behavior. To do so, we illustrate how cross-cultural research in the past two decades has enabled us to reconceptualize constructs, revise models, and extend boundary conditions in traditional organizational behavior theories. We focus on three domains-teams, leadership, and conflict-and review cross-cultural empirical evidence that has extended several theories in each of these domains. We support the claim that even well-established organizational behavior theories vary in the extent to which they may be applied unilaterally across cultures, thus identifying the critical need to advance these theories via a cross-cultural research agenda. © The Author(s) 2010.

Interfacial mixing in high energy-density matter with a multiphysics kinetic model

NASA Astrophysics Data System (ADS)

Haack, Jeff; Hauck, Cory; Murillo, Michael

2017-10-01

We have extended a recently-developed multispecies, multitemperature BGK model to include multiphysics capability that allows modeling of a wider range of plasma conditions. In particular, we have extended the model to describe one spatial dimension, and included a multispecies atomic ionization model, accurate collision physics across coupling regimes, self-consistent electric fields, and degeneracy in the electronic screening. We apply the new model to a warm dense matter scenario in which the ablator-fuel interface of an inertial confinement fusion target is heated, similar to a recent molecular dynamics study, but for larger length and time scales and for much higher temperatures. From our numerical results we are able to explore a variety of phenomena, including hydrogen jetting, kinetic effects (non-Maxwellian and anisotropic distributions), plasma physics (size, persistence and role of electric fields) and transport (relative sizes of Fickean diffision, electrodiffusion and barodiffusion). As compared with the recent molecular dynamics work the kinetic model greatly extends the accessible physical domains we are able to model.

Coupled Data Assimilation for Integrated Earth System Analysis and Prediction: Goals, Challenges, and Recommendations

NASA Technical Reports Server (NTRS)

Penny, Stephen G.; Akella, Santha; Buehner, Mark; Chevallier, Matthieu; Counillon, Francois; Draper, Clara; Frolov, Sergey; Fujii, Yosuke; Karspeck, Alicia; Kumar, Arun

2017-01-01

The purpose of this report is to identify fundamental issues for coupled data assimilation (CDA), such as gaps in science and limitations in forecasting systems, in order to provide guidance to the World Meteorological Organization (WMO) on how to facilitate more rapid progress internationally. Coupled Earth system modeling provides the opportunity to extend skillful atmospheric forecasts beyond the traditional two-week barrier by extracting skill from low-frequency state components such as the land, ocean, and sea ice. More generally, coupled models are needed to support seamless prediction systems that span timescales from weather, subseasonal to seasonal (S2S), multiyear, and decadal. Therefore, initialization methods are needed for coupled Earth system models, either applied to each individual component (called Weakly Coupled Data Assimilation - WCDA) or applied the coupled Earth system model as a whole (called Strongly Coupled Data Assimilation - SCDA). Using CDA, in which model forecasts and potentially the state estimation are performed jointly, each model domain benefits from observations in other domains either directly using error covariance information known at the time of the analysis (SCDA), or indirectly through flux interactions at the model boundaries (WCDA). Because the non-atmospheric domains are generally under-observed compared to the atmosphere, CDA provides a significant advantage over single-domain analyses. Next, we provide a synopsis of goals, challenges, and recommendations to advance CDA: Goals: (a) Extend predictive skill beyond the current capability of NWP (e.g. as demonstrated by improving forecast skill scores), (b) produce physically consistent initial conditions for coupled numerical prediction systems and reanalyses (including consistent fluxes at the domain interfaces), (c) make best use of existing observations by allowing observations from each domain to influence and improve the full earth system analysis, (d) develop a robust observation-based identification and understanding of mechanisms that determine the variability of weather and climate, (e) identify critical weaknesses in coupled models and the earth observing system, (f) generate full-field estimates of unobserved or sparsely observed variables, (g) improve the estimation of the external forcings causing changes to climate, (h) transition successes from idealized CDA experiments to real-world applications. Challenges: (a) Modeling at the interfaces between interacting components of coupled Earth system models may be inadequate for estimating uncertainty or error covariances between domains, (b) current data assimilation methods may be insufficient to simultaneously analyze domains containing multiple spatiotemporal scales of interest, (c) there is no standardization of observation data or their delivery systems across domains, (d) the size and complexity of many large-scale coupled Earth system models makes it is difficult to accurately represent uncertainty due to model parameters and coupling parameters, (e) model errors lead to local biases that can transfer between the different Earth system components and lead to coupled model biases and long-term model drift, (e) information propagation across model components with different spatiotemporal scales is extremely complicated, and must be improved in current coupled modeling frameworks, (h) there is insufficient knowledge on how to represent evolving errors in non-atmospheric model components (e.g. as sea ice, land and ocean) on the timescales of NWP.

Reconstruction of instantaneous surface normal velocity of a vibrating structure using interpolated time-domain equivalent source method

NASA Astrophysics Data System (ADS)

Geng, Lin; Bi, Chuan-Xing; Xie, Feng; Zhang, Xiao-Zheng

2018-07-01

Interpolated time-domain equivalent source method is extended to reconstruct the instantaneous surface normal velocity of a vibrating structure by using the time-evolving particle velocity as the input, which provides a non-contact way to overall understand the instantaneous vibration behavior of the structure. In this method, the time-evolving particle velocity in the near field is first modeled by a set of equivalent sources positioned inside the vibrating structure, and then the integrals of equivalent source strengths are solved by an iterative solving process and are further used to calculate the instantaneous surface normal velocity. An experiment of a semi-cylindrical steel plate impacted by a steel ball is investigated to examine the ability of the extended method, where the time-evolving normal particle velocity and pressure on the hologram surface measured by a Microflown pressure-velocity probe are used as the inputs of the extended method and the method based on pressure measurements, respectively, and the instantaneous surface normal velocity of the plate measured by a laser Doppler vibrometry is used as the reference for comparison. The experimental results demonstrate that the extended method is a powerful tool to visualize the instantaneous surface normal velocity of a vibrating structure in both time and space domains and can obtain more accurate results than that of the method based on pressure measurements.

Space and power: young mothers' management of smoking in extended families in China.

PubMed

Mao, Aimei

2013-05-01

Multigenerational co-residence is a widespread phenomenon in China but there is little knowledge about the impact of power dynamics on smoking behaviors among extended family residents. Using a gender lens, this ethnographic study explored how young mothers in extended families in mainland China managed the smoking of their husbands and other family members. Analysis of data resulted in a model of 'two units-three domains' to reflect gendered relationships between young mothers and other family members, and young mothers' participation in family management. Exploration of the mothers' efforts to deal with household smoking using the model provided an explanation for why the young mothers had limited control over household space and could only impose partial restrictions on home smoking in the extended family. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exact extreme-value statistics at mixed-order transitions.

PubMed

Bar, Amir; Majumdar, Satya N; Schehr, Grégory; Mukamel, David

2016-05-01

We study extreme-value statistics for spatially extended models exhibiting mixed-order phase transitions (MOT). These are phase transitions that exhibit features common to both first-order (discontinuity of the order parameter) and second-order (diverging correlation length) transitions. We consider here the truncated inverse distance squared Ising model, which is a prototypical model exhibiting MOT, and study analytically the extreme-value statistics of the domain lengths The lengths of the domains are identically distributed random variables except for the global constraint that their sum equals the total system size L. In addition, the number of such domains is also a fluctuating variable, and not fixed. In the paramagnetic phase, we show that the distribution of the largest domain length l_{max} converges, in the large L limit, to a Gumbel distribution. However, at the critical point (for a certain range of parameters) and in the ferromagnetic phase, we show that the fluctuations of l_{max} are governed by novel distributions, which we compute exactly. Our main analytical results are verified by numerical simulations.

The Longitudinal Interplay of Students' Academic Self-Concepts and Achievements within and across Domains: Replicating and Extending the Reciprocal Internal/External Frame of Reference Model

ERIC Educational Resources Information Center

Niepel, Christoph; Brunner, Martin; Preckel, Franzis

2014-01-01

Students' cognitive and motivational profiles have a large impact on their academic careers. The development of such profiles can partly be explained by the reciprocal internal/external frame of reference model (RI/E model). The RI/E model predicts positive and negative longitudinal effects between academic self-concepts and achievements within…

A conceptual model for megaprogramming

NASA Technical Reports Server (NTRS)

Tracz, Will

1990-01-01

Megaprogramming is component-based software engineering and life-cycle management. Magaprogramming and its relationship to other research initiatives (common prototyping system/common prototyping language, domain specific software architectures, and software understanding) are analyzed. The desirable attributes of megaprogramming software components are identified and a software development model and resulting prototype megaprogramming system (library interconnection language extended by annotated Ada) are described.

Time Domain Stability Margin Assessment Method

NASA Technical Reports Server (NTRS)

Clements, Keith

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Time-Domain Stability Margin Assessment

NASA Technical Reports Server (NTRS)

Clements, Keith

2016-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

The role of internal duplication in the evolution of multi-domain proteins.

PubMed

Nacher, J C; Hayashida, M; Akutsu, T

2010-08-01

Many proteins consist of several structural domains. These multi-domain proteins have likely been generated by selective genome growth dynamics during evolution to perform new functions as well as to create structures that fold on a biologically feasible time scale. Domain units frequently evolved through a variety of genetic shuffling mechanisms. Here we examine the protein domain statistics of more than 1000 organisms including eukaryotic, archaeal and bacterial species. The analysis extends earlier findings on asymmetric statistical laws for proteome to a wider variety of species. While proteins are composed of a wide range of domains, displaying a power-law decay, the computation of domain families for each protein reveals an exponential distribution, characterizing a protein universe composed of a thin number of unique families. Structural studies in proteomics have shown that domain repeats, or internal duplicated domains, represent a small but significant fraction of genome. In spite of its importance, this observation has been largely overlooked until recently. We model the evolutionary dynamics of proteome and demonstrate that these distinct distributions are in fact rooted in an internal duplication mechanism. This process generates the contemporary protein structural domain universe, determines its reduced thickness, and tames its growth. These findings have important implications, ranging from protein interaction network modeling to evolutionary studies based on fundamental mechanisms governing genome expansion.

Exact model reduction of combinatorial reaction networks

PubMed Central

Conzelmann, Holger; Fey, Dirk; Gilles, Ernst D

2008-01-01

Background Receptors and scaffold proteins usually possess a high number of distinct binding domains inducing the formation of large multiprotein signaling complexes. Due to combinatorial reasons the number of distinguishable species grows exponentially with the number of binding domains and can easily reach several millions. Even by including only a limited number of components and binding domains the resulting models are very large and hardly manageable. A novel model reduction technique allows the significant reduction and modularization of these models. Results We introduce methods that extend and complete the already introduced approach. For instance, we provide techniques to handle the formation of multi-scaffold complexes as well as receptor dimerization. Furthermore, we discuss a new modeling approach that allows the direct generation of exactly reduced model structures. The developed methods are used to reduce a model of EGF and insulin receptor crosstalk comprising 5,182 ordinary differential equations (ODEs) to a model with 87 ODEs. Conclusion The methods, presented in this contribution, significantly enhance the available methods to exactly reduce models of combinatorial reaction networks. PMID:18755034

Predicting chromatin architecture from models of polymer physics.

PubMed

Bianco, Simona; Chiariello, Andrea M; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-03-01

We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches. To identify the nature of architectural domains and their molecular determinants within a principled approach, we discuss models based on polymer physics. We show that basic concepts of interacting polymer physics explain chromatin spatial organization across chromosomal scales and cell types. The 3D structure of genomic loci can be derived with high accuracy and its molecular determinants identified by crossing information with epigenomic databases. In particular, we illustrate the case of the Sox9 locus, linked to human congenital disorders. The model in-silico predictions on the effects of genomic rearrangements are confirmed by available 5C data. That can help establishing new diagnostic tools for diseases linked to chromatin mis-folding, such as congenital disorders and cancer.

Quantum model of a hysteresis in a single-domain magnetically soft ferromagnetic

NASA Astrophysics Data System (ADS)

Ignatiev, V. K.; Lebedev, N. G.; Orlov, A. A.

2018-01-01

A quantum model of a single-domain magnetically soft ferromagnetic is proposed. The α-Fe crystal in a state of the saturation magnetization and a variable magnetic field is considered as a sample. The method of an effective Hamiltonian, including the operators of the Zeeman energy, the spin-orbit interaction and the interaction with the crystal field, is used in the model. An expansion of trial single-electron wave function in a series in small parameter of the spin-orbit interaction is suggested to account for the magnetic anisotropy. Within the framework of the Heisenberg representation, the nonlinear equations of motion for the magnetization and the orbital moment of single domain are obtained. Parameters of the modelling Hamiltonian are found from a comparison with experimental data on the magnetic anisotropy of iron. A phenomenological term of the magnetic friction is introduced into equation of the magnetization motion. Nonlinear equations are solved numerically by the Runge-Kutta method. A dependence of the single domain magnetization on magnetic field intensity has a characteristic form of a hysteresis loop which parameters are quantitatively coordinated with experimental data of researches of magnetic properties of nanoparticles of iron and iron oxide. The method is extended for modelling the magnetization dynamics of multi-domain ferromagnetic in the approximation of a strong crystal field.

Unsupervised Domain Adaptation with Multiple Acoustic Models

DTIC Science & Technology

2010-12-01

Discriminative MAP Adaptation Standard ML-MAP has been extended to incorporate discrim- inative training criteria such as MMI and MPE [10]. Dis- criminative MAP...smoothing variable I . For example, the MMI - MAP mean is given by ( mmi -map) jm = fnumjm (O) den jm(O)g+Djm̂jm + I (ml-map) jm f numjm den... MMI training, and Djm is the Gaussian-dependent parameter for the extended Baum-Welch (EBW) algorithm. MMI -MAP has been successfully applied in

Structured prediction models for RNN based sequence labeling in clinical text.

PubMed

Jagannatha, Abhyuday N; Yu, Hong

2016-11-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

Structured prediction models for RNN based sequence labeling in clinical text

PubMed Central

Jagannatha, Abhyuday N; Yu, Hong

2016-01-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

Xenon and Other Volatile Anesthetics Change Domain Structure in Model Lipid Raft Membranes

PubMed Central

Weinrich, Michael; Worcester, David L.

2014-01-01

Inhalation anesthetics have been in clinical use for over 160 years, but the molecular mechanisms of action continue to be investigated. Direct interactions with ion channels received much attention after it was found that anesthetics do not change the structure of homogeneous model membranes. However, it was recently found that halothane, a prototypical anesthetic, changes domain structure of a binary lipid membrane. The noble gas xenon is an excellent anesthetic and provides a pivotal test of the generality of this finding, extended to ternary lipid raft mixtures. We report that xenon and conventional anesthetics change the domain equilibrium in two canonical ternary lipid raft mixtures. These findings demonstrate a membrane-mediated mechanism whereby inhalation anesthetics can affect the lipid environment of trans-membrane proteins. PMID:24299622

Rice Cellulose SynthaseA8 Plant-Conserved Region Is a Coiled-Coil at the Catalytic Core Entrance1[OPEN

PubMed Central

Rushton, Phillip S.; Olek, Anna T.; Makowski, Lee; Badger, John

2017-01-01

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 Å resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecular envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery. PMID:27879387

Anti-levitation in integer quantum Hall systems

NASA Astrophysics Data System (ADS)

Wang, C.; Avishai, Y.; Meir, Yigal; Wang, X. R.

2014-01-01

The evolution of extended states of two-dimensional electron gas with white-noise randomness and field is numerically investigated by using the Anderson model on square lattices. Focusing on the lowest Landau band we establish an anti-levitation scenario of the extended states: As either the disorder strength W increases or the magnetic field strength B decreases, the energies of the extended states move below the Landau energies pertaining to a clean system. Moreover, for strong enough disorder, there is a disorder-dependent critical magnetic field Bc(W) below which there are no extended states at all. A general phase diagram in the W-1/B plane is suggested with a line separating domains of localized and delocalized states.

Ontology Design Patterns as Interfaces (invited)

NASA Astrophysics Data System (ADS)

Janowicz, K.

2015-12-01

In recent years ontology design patterns (ODP) have gained popularity among knowledge engineers. ODPs are modular but self-contained building blocks that are reusable and extendible. They minimize the amount of ontological commitments and thereby are easier to integrate than large monolithic ontologies. Typically, patterns are not directly used to annotate data or to model certain domain problems but are combined and extended to form data and purpose-driven local ontologies that serve the needs of specific applications or communities. By relying on a common set of patterns these local ontologies can be aligned to improve interoperability and enable federated queries without enforcing a top-down model of the domain. In previous work, we introduced ontological views as layer on top of ontology design patterns to ease the reuse, combination, and integration of patterns. While the literature distinguishes multiple types of patterns, e.g., content patterns or logical patterns, we propose to use them as interfaces here to guide the development of ontology-driven systems.

Optimization Testbed Cometboards Extended into Stochastic Domain

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Pai, Shantaram S.; Coroneos, Rula M.; Patnaik, Surya N.

2010-01-01

COMparative Evaluation Testbed of Optimization and Analysis Routines for the Design of Structures (CometBoards) is a multidisciplinary design optimization software. It was originally developed for deterministic calculation. It has now been extended into the stochastic domain for structural design problems. For deterministic problems, CometBoards is introduced through its subproblem solution strategy as well as the approximation concept in optimization. In the stochastic domain, a design is formulated as a function of the risk or reliability. Optimum solution including the weight of a structure, is also obtained as a function of reliability. Weight versus reliability traced out an inverted-S-shaped graph. The center of the graph corresponded to 50 percent probability of success, or one failure in two samples. A heavy design with weight approaching infinity could be produced for a near-zero rate of failure that corresponded to unity for reliability. Weight can be reduced to a small value for the most failure-prone design with a compromised reliability approaching zero. The stochastic design optimization (SDO) capability for an industrial problem was obtained by combining three codes: MSC/Nastran code was the deterministic analysis tool, fast probabilistic integrator, or the FPI module of the NESSUS software, was the probabilistic calculator, and CometBoards became the optimizer. The SDO capability requires a finite element structural model, a material model, a load model, and a design model. The stochastic optimization concept is illustrated considering an academic example and a real-life airframe component made of metallic and composite materials.

Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

PubMed Central

Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

2016-01-01

Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

Time Domain Stability Margin Assessment of the NASA Space Launch System GN&C Design for Exploration Mission One

NASA Technical Reports Server (NTRS)

Clements, Keith; Wall, John

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Time Domain Stability Margin Assessment of the NS Space Launch System GN&C Design for Exploration Mission One

NASA Technical Reports Server (NTRS)

Clements, Keith; Wall, John

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Finite difference time domain electromagnetic scattering from frequency-dependent lossy materials

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.

1991-01-01

Four different FDTD computer codes and companion Radar Cross Section (RCS) conversion codes on magnetic media are submitted. A single three dimensional dispersive FDTD code for both dispersive dielectric and magnetic materials was developed, along with a user's manual. The extension of FDTD to more complicated materials was made. The code is efficient and is capable of modeling interesting radar targets using a modest computer workstation platform. RCS results for two different plate geometries are reported. The FDTD method was also extended to computing far zone time domain results in two dimensions. Also the capability to model nonlinear materials was incorporated into FDTD and validated.

AN OVERVIEW OF EPANET VERSION 3.0

EPA Science Inventory

EPANET is a widely used public domain software package for modeling the hydraulic and water quality behavior of water distribution systems over an extended period of time. The last major update to the code was version 2.0 released in 2000 (Rossman, 2000). Since that time there ha...

A future Outlook: Web based Simulation of Hydrodynamic models

NASA Astrophysics Data System (ADS)

Islam, A. S.; Piasecki, M.

2003-12-01

Despite recent advances to present simulation results as 3D graphs or animation contours, the modeling user community still faces some shortcomings when trying to move around and analyze data. Typical problems include the lack of common platforms with standard vocabulary to exchange simulation results from different numerical models, insufficient descriptions about data (metadata), lack of robust search and retrieval tools for data, and difficulties to reuse simulation domain knowledge. This research demonstrates how to create a shared simulation domain in the WWW and run a number of models through multi-user interfaces. Firstly, meta-datasets have been developed to describe hydrodynamic model data based on geographic metadata standard (ISO 19115) that has been extended to satisfy the need of the hydrodynamic modeling community. The Extended Markup Language (XML) is used to publish this metadata by the Resource Description Framework (RDF). Specific domain ontology for Web Based Simulation (WBS) has been developed to explicitly define vocabulary for the knowledge based simulation system. Subsequently, this knowledge based system is converted into an object model using Meta Object Family (MOF). The knowledge based system acts as a Meta model for the object oriented system, which aids in reusing the domain knowledge. Specific simulation software has been developed based on the object oriented model. Finally, all model data is stored in an object relational database. Database back-ends help store, retrieve and query information efficiently. This research uses open source software and technology such as Java Servlet and JSP, Apache web server, Tomcat Servlet Engine, PostgresSQL databases, Protégé ontology editor, RDQL and RQL for querying RDF in semantic level, Jena Java API for RDF. Also, we use international standards such as the ISO 19115 metadata standard, and specifications such as XML, RDF, OWL, XMI, and UML. The final web based simulation product is deployed as Web Archive (WAR) files which is platform and OS independent and can be used by Windows, UNIX, or Linux. Keywords: Apache, ISO 19115, Java Servlet, Jena, JSP, Metadata, MOF, Linux, Ontology, OWL, PostgresSQL, Protégé, RDF, RDQL, RQL, Tomcat, UML, UNIX, Windows, WAR, XML

Mapping the Martian Meteorology

NASA Technical Reports Server (NTRS)

Allison, M.; Ross, J. D.; Solomon, N.

1999-01-01

The Mars-adapted version of the NASA/GISS general circulation model (GCM) has been applied to the hourly/daily simulation of the planet's meteorology over several seasonal orbits. The current running version of the model includes a diurnal solar cycle, CO2 sublimation, and a mature parameterization of upper level wave drag with a vertical domain extending from the surface up to the 6microb level. The benchmark simulations provide a four-dimensional archive for the comparative evaluation of various schemes for the retrieval of winds from anticipated polar orbiter measurements of temperatures by the Pressure Modulator Infrared Radiometer. Additional information is contained in the original extended abstract.

Final Report from The University of Texas at Austin for DEGAS: Dynamic Global Address Space programming environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erez, Mattan; Yelick, Katherine; Sarkar, Vivek

The Dynamic, Exascale Global Address Space programming environment (DEGAS) project will develop the next generation of programming models and runtime systems to meet the challenges of Exascale computing. Our approach is to provide an efficient and scalable programming model that can be adapted to application needs through the use of dynamic runtime features and domain-specific languages for computational kernels. We address the following technical challenges: Programmability: Rich set of programming constructs based on a Hierarchical Partitioned Global Address Space (HPGAS) model, demonstrated in UPC++. Scalability: Hierarchical locality control, lightweight communication (extended GASNet), and ef- ficient synchronization mechanisms (Phasers). Performance Portability:more » Just-in-time specialization (SEJITS) for generating hardware-specific code and scheduling libraries for domain-specific adaptive runtimes (Habanero). Energy Efficiency: Communication-optimal code generation to optimize energy efficiency by re- ducing data movement. Resilience: Containment Domains for flexible, domain-specific resilience, using state capture mechanisms and lightweight, asynchronous recovery mechanisms. Interoperability: Runtime and language interoperability with MPI and OpenMP to encourage broad adoption.« less

Study of human phonation in a full-body domain

NASA Astrophysics Data System (ADS)

Saurabh, Shakti; Bodony, Daniel

2015-11-01

The generation and propagation of the human voice is studied in two-dimensions using a full-body domain, using direct numerical simulation. The fluid/air in the vocal tract is modeled as a compressible and viscous fluid interacting with the non-linear, viscoelastic vocal folds (VF). The VF tissue material properties are multi-layered, with varying stiffness, and a finite-strain model is utilized and implemented in a quadratic finite element code. The fluid-solid domains are coupled through a boundary-fitted interface and utilize a Poisson equation-based mesh deformation method. The full-body domain includes the near VF region, the vocal tract, a simplified model of the soft palate and mouth, and extends out into the acoustic far-field. A new kind of inflow boundary condition based upon a quasi-one-dimensional formulation with constant sub-glottal volume velocity, which is linked to the VF movement, has been adopted. The sound pressure levels (SPL) measured are realistic and we analyze their connection to the VF dynamics and glottal and vocal tract geometries. Supported by the National Science Foundation (CAREER award number 1150439).

Sound source identification and sound radiation modeling in a moving medium using the time-domain equivalent source method.

PubMed

Zhang, Xiao-Zheng; Bi, Chuan-Xing; Zhang, Yong-Bin; Xu, Liang

2015-05-01

Planar near-field acoustic holography has been successfully extended to reconstruct the sound field in a moving medium, however, the reconstructed field still contains the convection effect that might lead to the wrong identification of sound sources. In order to accurately identify sound sources in a moving medium, a time-domain equivalent source method is developed. In the method, the real source is replaced by a series of time-domain equivalent sources whose strengths are solved iteratively by utilizing the measured pressure and the known convective time-domain Green's function, and time averaging is used to reduce the instability in the iterative solving process. Since these solved equivalent source strengths are independent of the convection effect, they can be used not only to identify sound sources but also to model sound radiations in both moving and static media. Numerical simulations are performed to investigate the influence of noise on the solved equivalent source strengths and the effect of time averaging on reducing the instability, and to demonstrate the advantages of the proposed method on the source identification and sound radiation modeling.

Data-Flow Based Model Analysis

NASA Technical Reports Server (NTRS)

Saad, Christian; Bauer, Bernhard

2010-01-01

The concept of (meta) modeling combines an intuitive way of formalizing the structure of an application domain with a high expressiveness that makes it suitable for a wide variety of use cases and has therefore become an integral part of many areas in computer science. While the definition of modeling languages through the use of meta models, e.g. in Unified Modeling Language (UML), is a well-understood process, their validation and the extraction of behavioral information is still a challenge. In this paper we present a novel approach for dynamic model analysis along with several fields of application. Examining the propagation of information along the edges and nodes of the model graph allows to extend and simplify the definition of semantic constraints in comparison to the capabilities offered by e.g. the Object Constraint Language. Performing a flow-based analysis also enables the simulation of dynamic behavior, thus providing an "abstract interpretation"-like analysis method for the modeling domain.

Analysis of random structure-acoustic interaction problems using coupled boundary element and finite element methods

NASA Technical Reports Server (NTRS)

Mei, Chuh; Pates, Carl S., III

1994-01-01

A coupled boundary element (BEM)-finite element (FEM) approach is presented to accurately model structure-acoustic interaction systems. The boundary element method is first applied to interior, two and three-dimensional acoustic domains with complex geometry configurations. Boundary element results are very accurate when compared with limited exact solutions. Structure-interaction problems are then analyzed with the coupled FEM-BEM method, where the finite element method models the structure and the boundary element method models the interior acoustic domain. The coupled analysis is compared with exact and experimental results for a simplistic model. Composite panels are analyzed and compared with isotropic results. The coupled method is then extended for random excitation. Random excitation results are compared with uncoupled results for isotropic and composite panels.

Creative Ventures: Mysteries and UFO's.

ERIC Educational Resources Information Center

Stark, Rebecca

This book published in 1987 provides open-ended activities to extend the imagination and creativity of students and encourage them to examine their feelings and values. Williams' model of cognitive-intellective and affective-feeling domains are addressed. Nearly 60 pages of exercises focus on the historical, the scientific, the mysterious, the…

Relating conformation to function in integrin α5β1.

PubMed

Su, Yang; Xia, Wei; Li, Jing; Walz, Thomas; Humphries, Martin J; Vestweber, Dietmar; Cabañas, Carlos; Lu, Chafen; Springer, Timothy A

2016-07-05

Whether β1 integrin ectodomains visit conformational states similarly to β2 and β3 integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to β1 integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin α5β1 ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the α5 or β1 legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the β1 βI domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open βI domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the βI domain and βI-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of α5β1 is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to α5β1 on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.

A Dual-Process Approach to the Role of Mother's Implicit and Explicit Attitudes toward Their Child in Parenting Models

ERIC Educational Resources Information Center

Sturge-Apple, Melissa L.; Rogge, Ronald D.; Skibo, Michael A.; Peltz, Jack S.; Suor, Jennifer H.

2015-01-01

Extending dual process frameworks of cognition to a novel domain, the present study examined how mothers' explicit and implicit attitudes about her child may operate in models of parenting. To assess implicit attitudes, two separate studies were conducted using the same child-focused Go/No-go Association Task (GNAT-Child). In Study 1, model…

Downstream Effects on Orbiter Leeside Flow Separation for Hypersonic Flows

NASA Technical Reports Server (NTRS)

Buck, Gregory M.; Pulsonetti, Maria V.; Weilmuenster, K. James

2005-01-01

Discrepancies between experiment and computation for shuttle leeside flow separation, which came to light in the Columbia accident investigation, are resolved. Tests were run in the Langley Research Center 20-Inch Hypersonic CF4 Tunnel with a baseline orbiter model and two extended trailing edge models. The extended trailing edges altered the wing leeside separation lines, moving the lines toward the fuselage, proving that wing trailing edge modeling does affect the orbiter leeside flow. Computations were then made with a wake grid. These calculations more closely matched baseline experiments. Thus, the present findings demonstrate that it is imperative to include the wake flow domain in CFD calculations in order to accurately predict leeside flow separation for hypersonic vehicles at high angles of attack.

Prediction of multiple resonance characteristics by an extended resistor-inductor-capacitor circuit model for plasmonic metamaterials absorbers in infrared.

PubMed

Xu, Xiaolun; Li, Yongqian; Wang, Binbin; Zhou, Zili

2015-10-01

The resonance characteristics of plasmonic metamaterials absorbers (PMAs) are strongly dependent on geometric parameters. A resistor-inductor-capacitor (RLC) circuit model has been extended to predict the resonance wavelengths and the bandwidths of multiple magnetic polaritons modes in PMAs. For a typical metallic-dielectric-metallic structure absorber working in the infrared region, the developed model describes the correlation between the resonance characteristics and the dimensional sizes. In particular, the RLC model is suitable for not only the fundamental resonance mode, but also for the second- and third-order resonance modes. The prediction of the resonance characteristics agrees fairly well with those calculated by the finite-difference time-domain simulation and the experimental results. The developed RLC model enables the facilitation of designing multi-band PMAs for infrared radiation detectors and thermal emitters.

Extending the Utility of the Parabolic Approximation in Medical Ultrasound Using Wide-Angle Diffraction Modeling.

PubMed

Soneson, Joshua E

2017-04-01

Wide-angle parabolic models are commonly used in geophysics and underwater acoustics but have seen little application in medical ultrasound. Here, a wide-angle model for continuous-wave high-intensity ultrasound beams is derived, which approximates the diffraction process more accurately than the commonly used Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation without increasing implementation complexity or computing time. A method for preventing the high spatial frequencies often present in source boundary conditions from corrupting the solution is presented. Simulations of shallowly focused axisymmetric beams using both the wide-angle and standard parabolic models are compared to assess the accuracy with which they model diffraction effects. The wide-angle model proposed here offers improved focusing accuracy and less error throughout the computational domain than the standard parabolic model, offering a facile method for extending the utility of existing KZK codes.

The extended Fourier pseudospectral time-domain method for atmospheric sound propagation.

PubMed

Hornikx, Maarten; Waxler, Roger; Forssén, Jens

2010-10-01

An extended Fourier pseudospectral time-domain (PSTD) method is presented to model atmospheric sound propagation by solving the linearized Euler equations. In this method, evaluation of spatial derivatives is based on an eigenfunction expansion. Evaluation on a spatial grid requires only two spatial points per wavelength. Time iteration is done using a low-storage optimized six-stage Runge-Kutta method. This method is applied to two-dimensional non-moving media models, one with screens and one for an urban canyon, with generally high accuracy in both amplitude and phase. For a moving atmosphere, accurate results have been obtained in models with both a uniform and a logarithmic wind velocity profile over a rigid ground surface and in the presence of a screen. The method has also been validated for three-dimensional sound propagation over a screen. For that application, the developed method is in the order of 100 times faster than the second-order-accurate FDTD solution to the linearized Euler equations. The method is found to be well suited for atmospheric sound propagation simulations where effects of complex meteorology and straight rigid boundary surfaces are to be investigated.

Implementation of a boundary element method to solve for the near field effects of an array of WECs

NASA Astrophysics Data System (ADS)

Oskamp, J. A.; Ozkan-Haller, H. T.

2010-12-01

When Wave Energy Converters (WECs) are installed, they affect the shoreline wave climate by removing some of the wave energy which would have reached the shore. Before large WEC projects are launched, it is important to understand the potential coastal impacts of these installations. The high cost associated with ocean scale testing invites the use of hydrodynamic models to play a major role in estimating these effects. In this study, a wave structure interaction program (WAMIT) is used to model an array of WECs. The program predicts the wave field throughout the array using a boundary element method to solve the potential flow fluid problem, taking into account the incident waves, the power dissipated, and the way each WEC moves and interacts with the others. This model is appropriate for a small domain near the WEC array in order to resolve the details in the interactions, but not extending to the coastline (where the far-field effects must be assessed). To propagate these effects to the coastline, the waves leaving this small domain will be used as boundary conditions for a larger model domain which will assess the shoreline effects caused by the array. The immediate work is concerned with setting up the WAMIT model for a small array of point absorbers. A 1:33 scale lab test is planned and will provide data to validate the WAMIT model on this small domain before it is nested with the larger domain to estimate shoreline effects.

A methodology for extending domain coverage in SemRep.

PubMed

Rosemblat, Graciela; Shin, Dongwook; Kilicoglu, Halil; Sneiderman, Charles; Rindflesch, Thomas C

2013-12-01

We describe a domain-independent methodology to extend SemRep coverage beyond the biomedical domain. SemRep, a natural language processing application originally designed for biomedical texts, uses the knowledge sources provided by the Unified Medical Language System (UMLS©). Ontological and terminological extensions to the system are needed in order to support other areas of knowledge. We extended SemRep's application by developing a semantic representation of a previously unsupported domain. This was achieved by adapting well-known ontology engineering phases and integrating them with the UMLS knowledge sources on which SemRep crucially depends. While the process to extend SemRep coverage has been successfully applied in earlier projects, this paper presents in detail the step-wise approach we followed and the mechanisms implemented. A case study in the field of medical informatics illustrates how the ontology engineering phases have been adapted for optimal integration with the UMLS. We provide qualitative and quantitative results, which indicate the validity and usefulness of our methodology. Published by Elsevier Inc.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning.

PubMed

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-07-11

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.

Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

PubMed

Jiang, Jianwen; Taylor, Alexander B; Prasad, Kondury; Ishikawa-Brush, Yumiko; Hart, P John; Lafer, Eileen M; Sousa, Rui

2003-05-20

J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date. In addition to the canonical J-domain features described previously, the auxilin J-domain contains an extra N-terminal helix and a long loop inserted between helices I and II. The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70.

Partially coherent isodiffracting pulsed beams

NASA Astrophysics Data System (ADS)

Koivurova, Matias; Ding, Chaoliang; Turunen, Jari; Pan, Liuzhan

2018-02-01

We investigate a class of isodiffracting pulsed beams, which are superpositions of transverse modes supported by spherical-mirror laser resonators. By employing modal weights that, for stationary light, produce a Gaussian Schell-model beam, we extend this standard model to pulsed beams. We first construct the two-frequency cross-spectral density function that characterizes the spatial coherence in the space-frequency domain. By assuming a power-exponential spectral profile, we then employ the generalized Wiener-Khintchine theorem for nonstationary light to derive the two-time mutual coherence function that describes the space-time coherence of the ensuing beams. The isodiffracting nature of the laser resonator modes permits all (paraxial-domain) calculations at any propagation distance to be performed analytically. Significant spatiotemporal coupling is revealed in subcycle, single-cycle, and few-cycle domains, where the partial spatial coherence also leads to reduced temporal coherence even though full spectral coherence is assumed.

Dislocation dynamics in non-convex domains using finite elements with embedded discontinuities

NASA Astrophysics Data System (ADS)

Romero, Ignacio; Segurado, Javier; LLorca, Javier

2008-04-01

The standard strategy developed by Van der Giessen and Needleman (1995 Modelling Simul. Mater. Sci. Eng. 3 689) to simulate dislocation dynamics in two-dimensional finite domains was modified to account for the effect of dislocations leaving the crystal through a free surface in the case of arbitrary non-convex domains. The new approach incorporates the displacement jumps across the slip segments of the dislocations that have exited the crystal within the finite element analysis carried out to compute the image stresses on the dislocations due to the finite boundaries. This is done in a simple computationally efficient way by embedding the discontinuities in the finite element solution, a strategy often used in the numerical simulation of crack propagation in solids. Two academic examples are presented to validate and demonstrate the extended model and its implementation within a finite element program is detailed in the appendix.

Thermal runaway and microwave heating in thin cylindrical domains

NASA Astrophysics Data System (ADS)

Ward, Michael J.

2002-04-01

The behaviour of the solution to two nonlinear heating problems in a thin cylinder of revolution of variable cross-sectional area is analysed using asymptotic and numerical methods. The first problem is to calculate the fold point, corresponding to the onset of thermal runaway, for a steady-state nonlinear elliptic equation that arises in combustion theory. In the limit of thin cylindrical domains, it is shown that the onset of thermal runaway can be delayed when a circular cylindrical domain is perturbed into a dumbell shape. Numerical values for the fold point for different domain shapes are obtained asymptotically and numerically. The second problem that is analysed is a nonlinear parabolic equation modelling the microwave heating of a ceramic cylinder by a known electric field. The basic model in a thin circular cylindrical domain was analysed in Booty & Kriegsmann (Meth. Appl. Anal. 4 (1994) p. 403). Their analysis is extended to treat thin cylindrical domains of variable cross-section. It is shown that the steady-state and dynamic behaviours of localized regions of high temperature, called hot-spots, depend on a competition between the maxima of the electric field and the maximum deformation of the circular cylinder. For a dumbell-shaped region it is shown that two disconnected hot-spot regions can occur. Depending on the parameters in the model, these regions, ultimately, either merge as time increases or else remain as disconnected regions for all time.

The Internal/External Frame of Reference of Academic Self-Concept: Extension to a Foreign Language and the Role of Language of Instruction

ERIC Educational Resources Information Center

Xu, Man K.; Marsh, Herbert W.; Hau, Kit-Tai; Ho, Irene T.; Morin, Alexandre J. S.; Abduljabbar, Adel S.

2013-01-01

The internal/external frame of reference (I/E) model (Marsh, 1986) posits that the effects of contrasting math and verbal domains of achievement are positive for matching academic self-concepts (ASCs) but negative for nonmatching ASCs (i.e., math achievement on verbal ASC; verbal achievement on math ASC). We extend the classic I/E model by…

Predictive Simulation of Material Failure Using Peridynamics -- Advanced Constitutive Modeling, Verification and Validation

DTIC Science & Technology

2016-03-31

particular physical model under consideration. Therefore, in the following the enrichment functions are discussed with respect to particular...some domains of influence are extended outside of the physical boundary, the reproducing conditions enforced in Eq. (6) guarantee the order of...often used in astrophysics problems, where many fluid problems are encountered and even “solid" bodies deform under their own gravity. It can also

From Theory to Data: The Process of Refining Learning Progressions

ERIC Educational Resources Information Center

Shea, Nicole A.; Duncan, Ravit Golan

2013-01-01

Learning progressions (LPs) are theoretical models of how learners develop expertise in a domain over extended periods of time. Recent policy reports have touted LPs as a promising approach to aligning standards, curriculum, and assessment. However, the scholarship on LPs is relatively sparse, and the jury is still out on the theoretical and…

Structure and dynamics of zymogen human blood coagulation factor X.

PubMed

Venkateswarlu, Divi; Perera, Lalith; Darden, Tom; Pedersen, Lee G

2002-03-01

The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-A-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing gamma-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be approximately 95 A in contrast to approximately 83 A in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.

Simulations of Cyclone Sidr in the Bay of Bengal with a High-Resolution Model: Sensitivity to Large-Scale Boundary Forcing

NASA Technical Reports Server (NTRS)

Kumar, Anil; Done, James; Dudhia, Jimy; Niyogi, Dev

2011-01-01

The predictability of Cyclone Sidr in the Bay of Bengal was explored in terms of track and intensity using the Advanced Research Hurricane Weather Research Forecast (AHW) model. This constitutes the first application of the AHW over an area that lies outside the region of the North Atlantic for which this model was developed and tested. Several experiments were conducted to understand the possible contributing factors that affected Sidr s intensity and track simulation by varying the initial start time and domain size. Results show that Sidr s track was strongly controlled by the synoptic flow at the 500-hPa level, seen especially due to the strong mid-latitude westerly over north-central India. A 96-h forecast produced westerly winds over north-central India at the 500-hPa level that were notably weaker; this likely caused the modeled cyclone track to drift from the observed actual track. Reducing the model domain size reduced model error in the synoptic-scale winds at 500 hPa and produced an improved cyclone track. Specifically, the cyclone track appeared to be sensitive to the upstream synoptic flow, and was, therefore, sensitive to the location of the western boundary of the domain. However, cyclone intensity remained largely unaffected by this synoptic wind error at the 500-hPa level. Comparison of the high resolution, moving nested domain with a single coarser resolution domain showed little difference in tracks, but resulted in significantly different intensities. Experiments on the domain size with regard to the total precipitation simulated by the model showed that precipitation patterns and 10-m surface winds were also different. This was mainly due to the mid-latitude westerly flow across the west side of the model domain. The analysis also suggested that the total precipitation pattern and track was unchanged when the domain was extended toward the east, north, and south. Furthermore, this highlights our conclusion that Sidr was influenced from the west side of the domain. The displacement error was significantly reduced after the domain size from the western model boundary was decreased. Study results demonstrate the capability and need of a high-resolution mesoscale modeling framework for simulating the complex interactions that contribute to the formation of tropical cyclones over the Bay of Bengal region

Low-lying Photoexcited States of a One-Dimensional Ionic Extended Hubbard Model

NASA Astrophysics Data System (ADS)

Yokoi, Kota; Maeshima, Nobuya; Hino, Ken-ichi

2017-10-01

We investigate the properties of low-lying photoexcited states of a one-dimensional (1D) ionic extended Hubbard model at half-filling. Numerical analysis by using the full and Lanczos diagonalization methods shows that, in the ionic phase, there exist low-lying photoexcited states below the charge transfer gap. As a result of comparison with numerical data for the 1D antiferromagnetic (AF) Heisenberg model, it was found that, for a small alternating potential Δ, these low-lying photoexcited states are spin excitations, which is consistent with a previous analytical study [Katsura et al., Phys. Rev. Lett. 103, 177402 (2009)]. As Δ increases, the spectral intensity of the 1D ionic extended Hubbard model rapidly deviates from that of the 1D AF Heisenberg model and it is clarified that this deviation is due to the neutral-ionic domain wall, an elementary excitation near the neutral-ionic transition point.

Conformational Rearrangement Within the Soluble Domains of the CD4 Receptor is Ligand-Specific

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashish,F.; Juncadella, I.; Garg, R.

2008-01-01

Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed thatmore » both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.« less

The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape*

PubMed Central

Carballido, Ana M.

2016-01-01

Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins contain a plakin domain formed by up to nine spectrin repeats (SR1–SR9) and an SH3 domain. The plakin domains of plectin and other plakins harbor binding sites for junctional proteins. We have combined x-ray crystallography with small angle x-ray scattering (SAXS) to elucidate the structure of the plakin domain of plectin, extending our previous analysis of the SR1 to SR5 region. Two crystal structures of the SR5-SR6 region allowed us to characterize its uniquely wide inter-repeat conformational variability. We also report the crystal structures of the SR7-SR8 region, refined to 1.8 Å, and the SR7–SR9 at lower resolution. The SR7–SR9 region, which is conserved in all other plakin domains, forms a rigid segment stabilized by uniquely extensive inter-repeat contacts mediated by unusually long helices in SR8 and SR9. Using SAXS we show that in solution the SR3–SR6 and SR7–SR9 regions are rod-like segments and that SR3–SR9 of plectin has an extended shape with a small central kink. Other plakins, such as bullous pemphigoid antigen 1 and microtubule and actin cross-linking factor 1, are likely to have similar extended plakin domains. In contrast, desmoplakin has a two-segment structure with a central flexible hinge. The continuous versus segmented structures of the plakin domains of plectin and desmoplakin give insight into how different plakins might respond to tension and transmit mechanical signals. PMID:27413182

Constitutive relations of ferroelectric ceramics

NASA Astrophysics Data System (ADS)

Su, Yu

The objective of this thesis is to obtain a better understanding on the fundamental constitutive behavior of ferroelectric ceramics based on the physics of phase transition, micromechanics of heterogeneous materials, and principles of irreversible thermodynamics. Within this framework, a self-consistent model is developed to investigate the electromechanical responses of ferroelectric polycrystals under temperature change and electromechanical loading. Cooling of a paraelectric crystal below its curie temperature Tc would result in spontaneous polarization, whereas electromechanical loading on a poled crystal could lead to domain switch. Domain growth and reorientation inside ferroelectric crystals are studied in light of these phase transition and domain switch. In this process, the change of the effective elastic, dielectric and piezoelectric constants during the evolution of microstructures are examined. In addition, hysteresis loops for the electric displacement and other related phenomena are computed under cyclic electric load. On top of all methods implemented in this work, the kinetic equation derived from the irreversible thermodynamics is the key to study the domain evolution in ferroelectric crystals. The kinetic relation not only governs the growth of new domain in a ferroelectric crystal, but it also determines the onset of phase transition. This characteristic is used to study the effect of hydrostatic pressure on the shift of Curie temperature of a ferroelectric crystal. Based on the derived expressions, it is observed that the deriving force can increase or decrease upon applied hydrostatic mechanical loading, depending on the change of electromechanical moduli, eigenstrain and electro-polarization. Several typical cases are computed and it is found that the change of the electromechanical moduli during phase transformation plays the key role in the shift of Curie temperature. Since ferroelectric ceramics are in a polycrystal form, a self-consistent model is used to examine the issues involved. In this model, each grain is represented by a spherical inclusion embedded in an infinitely extended piezoelectric matrix, and the inclusion further possesses an eigenstrain and eigen polarization. Secant relations between the polycrystal-matrix and the embedded inclusion are established by extending Hill's [1] incremental relations. An iterative computational program is developed for this self-consistent model.

Extended-Range High-Resolution Dynamical Downscaling over a Continental-Scale Domain

NASA Astrophysics Data System (ADS)

Husain, S. Z.; Separovic, L.; Yu, W.; Fernig, D.

2014-12-01

High-resolution mesoscale simulations, when applied for downscaling meteorological fields over large spatial domains and for extended time periods, can provide valuable information for many practical application scenarios including the weather-dependent renewable energy industry. In the present study, a strategy has been proposed to dynamically downscale coarse-resolution meteorological fields from Environment Canada's regional analyses for a period of multiple years over the entire Canadian territory. The study demonstrates that a continuous mesoscale simulation over the entire domain is the most suitable approach in this regard. Large-scale deviations in the different meteorological fields pose the biggest challenge for extended-range simulations over continental scale domains, and the enforcement of the lateral boundary conditions is not sufficient to restrict such deviations. A scheme has therefore been developed to spectrally nudge the simulated high-resolution meteorological fields at the different model vertical levels towards those embedded in the coarse-resolution driving fields derived from the regional analyses. A series of experiments were carried out to determine the optimal nudging strategy including the appropriate nudging length scales, nudging vertical profile and temporal relaxation. A forcing strategy based on grid nudging of the different surface fields, including surface temperature, soil-moisture, and snow conditions, towards their expected values obtained from a high-resolution offline surface scheme was also devised to limit any considerable deviation in the evolving surface fields due to extended-range temporal integrations. The study shows that ensuring large-scale atmospheric similarities helps to deliver near-surface statistical scores for temperature, dew point temperature and horizontal wind speed that are better or comparable to the operational regional forecasts issued by Environment Canada. Furthermore, the meteorological fields resulting from the proposed downscaling strategy have significantly improved spatiotemporal variance compared to those from the operational forecasts, and any time series generated from the downscaled fields do not suffer from discontinuities due to switching between the consecutive forecasts.

A UML profile for the OBO relation ontology.

PubMed

Guardia, Gabriela D A; Vêncio, Ricardo Z N; de Farias, Cléver R G

2012-01-01

Ontologies have increasingly been used in the biomedical domain, which has prompted the emergence of different initiatives to facilitate their development and integration. The Open Biological and Biomedical Ontologies (OBO) Foundry consortium provides a repository of life-science ontologies, which are developed according to a set of shared principles. This consortium has developed an ontology called OBO Relation Ontology aiming at standardizing the different types of biological entity classes and associated relationships. Since ontologies are primarily intended to be used by humans, the use of graphical notations for ontology development facilitates the capture, comprehension and communication of knowledge between its users. However, OBO Foundry ontologies are captured and represented basically using text-based notations. The Unified Modeling Language (UML) provides a standard and widely-used graphical notation for modeling computer systems. UML provides a well-defined set of modeling elements, which can be extended using a built-in extension mechanism named Profile. Thus, this work aims at developing a UML profile for the OBO Relation Ontology to provide a domain-specific set of modeling elements that can be used to create standard UML-based ontologies in the biomedical domain.

Applicability domain: towards a more formal definition.

PubMed

Hanser, T; Barber, C; Marchaland, J F; Werner, S

2016-11-01

In recent years the applicability domain (AD) of a prediction system has become an important concern in (Q)SAR modelling, especially in the context of human safety assessment. Today AD is an active research topic, and many methods have been designed to estimate the adequacy of a model and the confidence in its outcome for a given prediction task. Unfortunately, the wide spectrum of techniques developed for this purpose is based on various definitions of the concept of AD, often taking into account different types of information. This variety of methodologies confuses the end users and makes the comparison of the AD for different models almost impossible. In this article, we demonstrate that AD is not a monolithic concept and can be broken down into three well-defined sub-domains assessing confidence at the model, prediction and decision levels, respectively. By leveraging this separation of concerns we have an opportunity to clarify, formalize and extend the definition of AD. We propose a framework that captures this new vision with the aim to initiate a global effort to converge towards a common AD definition within the (Q)SAR community.

Time-domain simulation of damped impacted plates. II. Numerical model and results.

PubMed

Lambourg, C; Chaigne, A; Matignon, D

2001-04-01

A time-domain model for the flexural vibrations of damped plates was presented in a companion paper [Part I, J. Acoust. Soc. Am. 109, 1422-1432 (2001)]. In this paper (Part II), the damped-plate model is extended to impact excitation, using Hertz's law of contact, and is solved numerically in order to synthesize sounds. The numerical method is based on the use of a finite-difference scheme of second order in time and fourth order in space. As a consequence of the damping terms, the stability and dispersion properties of this scheme are modified, compared to the undamped case. The numerical model is used for the time-domain simulation of vibrations and sounds produced by impact on isotropic and orthotropic plates made of various materials (aluminum, glass, carbon fiber and wood). The efficiency of the method is validated by comparisons with analytical and experimental data. The sounds produced show a high degree of similarity with real sounds and allow a clear recognition of each constitutive material of the plate without ambiguity.

Time domain passivity controller for 4-channel time-delay bilateral teleoperation.

PubMed

Rebelo, Joao; Schiele, Andre

2015-01-01

This paper presents an extension of the time-domain passivity control approach to a four-channel bilateral controller under the effects of time delays. Time-domain passivity control has been used successfully to stabilize teleoperation systems with position-force and position-position controllers; however, the performance with such control architectures is sub-optimal both with and without time delays. This work extends the network representation of the time-domain passivity controller to the four-channel architecture, which provides perfect transparency to the user without time delay. The proposed architecture is based on modelling the controllers as dependent voltage sources and using only series passivity controllers. The obtained results are shown on a one degree-of-freedom setup and illustrate the stabilization behaviour of the proposed controller when time delay is present in the communication channel.

Human immunoglobulin E flexes between acutely bent and extended conformations

PubMed Central

Keeble, Anthony H; Wright, Michael; Cain, Katharine; Hailu, Hanna; Oxbrow, Amanda; Delgado, Jean; Shuttleworth, Lindsay K; Kao, Michael W-P; McDonnell, James M; Beavil, Andrew J; Henry, Alistair J; Sutton, Brian J

2014-01-01

Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cε2 domain pair folded back onto the Cε3-Cε4 domains, but is the molecule exclusively bent or can the Cε2 domains adopt extended conformations and even “flip” from one side of the molecule to the other? We report the crystal structure of IgE-Fc captured in a fully extended, symmetrical conformation and show by molecular dynamics, calorimetry, stopped-flow kinetic, SPR and FRET analyses, that the antibody can indeed adopt such extended conformations in solution. This diversity of conformational states available to IgE-Fc offers a new perspective on IgE function in allergen recognition, as part of the B cell receptor and as a therapeutic target in allergic disease. PMID:24632569

The Application of Deterministic Spectral Domain Method to the Analysis of Planar Circuit Discontinuities on Open Substrates

DTIC Science & Technology

1990-08-01

the spectral domain is extended to include the effects of two-dimensional, two-component current flow in planar transmission line discontinuities 6n...PROFESSOR: Tatsuo Itoh A deterministic formulation of the method of moments carried out in the spectral domain is extended to include the effects of...two-dimensional, two- component current flow in planar transmission line discontinuities on open substrates. The method includes the effects of space

The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

NASA Astrophysics Data System (ADS)

Moore, S. E.; Stabeno, P. J.

2016-02-01

The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

Extending the Serum Half-Life of G-CSF via Fusion with the Domain III of Human Serum Albumin

PubMed Central

Zhao, Shuqiang; Zhang, Yu; Tian, Hong; Chen, Xiaofei; Cai, Di; Yao, Wenbing; Gao, Xiangdong

2013-01-01

Protein fusion technology is one of the most commonly used methods to extend the half-life of therapeutic proteins. In this study, in order to prolong the half-life of Granulocyte colony stimulating factor (G-CSF), the domain III of human serum albumin (3DHSA) was genetically fused to the N-terminal of G-CSF. The 3DHSA-G-CSF fusion gene was cloned into pPICZαA along with the open reading frame of the α-factor signal under the control of the AOX1 promoter. The recombinant expression vector was transformed into Pichia pastoris GS115, and the recombinant strains were screened by SDS-PAGE. As expected, the 3DHSA-G-CSF showed high binding affinity with HSA antibody and G-CSF antibody, and the natural N-terminal of 3DHSA was detected by N-terminal sequencing. The bioactivity and pharmacokinetic studies of 3DHSA-G-CSF were respectively determined using neutropenia model mice and human G-CSF ELISA kit. The results demonstrated that 3DHSA-G-CSF has the ability to increase the peripheral white blood cell (WBC) counts of neutropenia model mice, and the half-life of 3DHSA-G-CSF is longer than that of native G-CSF. In conclusion, 3DHSA can be used to extend the half-life of G-CSF. PMID:24151579

Opposing effects of stacking faults and antisite domain boundaries on the conduction band edge in kesterite quaternary semiconductors

NASA Astrophysics Data System (ADS)

Park, Ji-Sang; Kim, Sunghyun; Walsh, Aron

2018-01-01

We investigated stability and the electronic structure of extended defects including antisite domain boundaries and stacking faults in the kesterite-structured semiconductors, Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe). Our hybrid density functional theory calculations show that stacking faults in CZTS and CZTSe induce a higher conduction band edge than the bulk counterparts, and thus the stacking faults act as electron barriers. Antisite domain boundaries, however, accumulate electrons as the conduction band edge is reduced in energy, having an opposite role. An Ising model was constructed to account for the stability of stacking faults, which shows the nearest-neighbor interaction is stronger in the case of the selenide.

Melting of Domain Wall in Charge Ordered Dirac Electron of Organic Conductor α-(BEDT-TTF)2I3

NASA Astrophysics Data System (ADS)

Ohki, Daigo; Matsuno, Genki; Omori, Yukiko; Kobayashi, Akito

2018-05-01

The origin of charge order melting is identified by using the real space dependent mean-field theory in the extended Hubbard model describing an organic Dirac electron system α-(BEDT-TTF)2I3. In this model, the width of a domain wall which arises between different types of the charge ordered phase exhibits a divergent increase with decreasing the strength of electron-electron correlations. By analyzing the finite-size effect carefully, it is shown that the divergence coincides with a topological transition where a pair of Dirac cones merges in keeping with a finite gap. It is also clarified that the gap opening point and the topological transition point are different, which leads to the existence of an exotic massive Dirac electron phase with melted-type domain wall and gapless edge states. The present result also indicated that multiple metastable states are emerged in massive Dirac Electron phase. In the trivial charge ordered phase, the gapless domain-wall bound state takes place instead of the gapless edge states, accompanying with a form change of the domain wall from melted-type into hyperbolic-tangent-type.

Multidisciplinary model-based-engineering for laser weapon systems: recent progress

NASA Astrophysics Data System (ADS)

Coy, Steve; Panthaki, Malcolm

2013-09-01

We are working to develop a comprehensive, integrated software framework and toolset to support model-based engineering (MBE) of laser weapons systems. MBE has been identified by the Office of the Director, Defense Science and Engineering as one of four potentially "game-changing" technologies that could bring about revolutionary advances across the entire DoD research and development and procurement cycle. To be effective, however, MBE requires robust underlying modeling and simulation technologies capable of modeling all the pertinent systems, subsystems, components, effects, and interactions at any level of fidelity that may be required in order to support crucial design decisions at any point in the system development lifecycle. Very often the greatest technical challenges are posed by systems involving interactions that cut across two or more distinct scientific or engineering domains; even in cases where there are excellent tools available for modeling each individual domain, generally none of these domain-specific tools can be used to model the cross-domain interactions. In the case of laser weapons systems R&D these tools need to be able to support modeling of systems involving combined interactions among structures, thermal, and optical effects, including both ray optics and wave optics, controls, atmospheric effects, target interaction, computational fluid dynamics, and spatiotemporal interactions between lasing light and the laser gain medium. To address this problem we are working to extend Comet™, to add the addition modeling and simulation capabilities required for this particular application area. In this paper we will describe our progress to date.

INTEGRATION OF SATELLITE, MODELED, AND GROUND BASED AEROSOL DATA FOR USE IN AIR QUALITY AND PUBLIC HEALTH APPLICATIONS ( AGU-BALTIMORE )

EPA Science Inventory

Within the next several years NOAA and EPA will begin to issue PM_2.5 air quality forecasts over the entire domain of the eastern United States, eventually extending to national coverage. These forecasts will provide continuous estimated values of particulate matter on ...

Design of broadband time-domain impedance boundary conditions using the oscillatory-diffusive representation of acoustical models.

PubMed

Monteghetti, Florian; Matignon, Denis; Piot, Estelle; Pascal, Lucas

2016-09-01

A methodology to design broadband time-domain impedance boundary conditions (TDIBCs) from the analysis of acoustical models is presented. The derived TDIBCs are recast exclusively as first-order differential equations, well-suited for high-order numerical simulations. Broadband approximations are yielded from an elementary linear least squares optimization that is, for most models, independent of the absorbing material geometry. This methodology relies on a mathematical technique referred to as the oscillatory-diffusive (or poles and cuts) representation, and is applied to a wide range of acoustical models, drawn from duct acoustics and outdoor sound propagation, which covers perforates, semi-infinite ground layers, as well as cavities filled with a porous medium. It is shown that each of these impedance models leads to a different TDIBC. Comparison with existing numerical models, such as multi-pole or extended Helmholtz resonator, provides insights into their suitability. Additionally, the broadly-applicable fractional polynomial impedance models are analyzed using fractional calculus.

Folk Theorems on the Correspondence between State-Based and Event-Based Systems

NASA Astrophysics Data System (ADS)

Reniers, Michel A.; Willemse, Tim A. C.

Kripke Structures and Labelled Transition Systems are the two most prominent semantic models used in concurrency theory. Both models are commonly believed to be equi-expressive. One can find many ad-hoc embeddings of one of these models into the other. We build upon the seminal work of De Nicola and Vaandrager that firmly established the correspondence between stuttering equivalence in Kripke Structures and divergence-sensitive branching bisimulation in Labelled Transition Systems. We show that their embeddings can also be used for a range of other equivalences of interest, such as strong bisimilarity, simulation equivalence, and trace equivalence. Furthermore, we extend the results by De Nicola and Vaandrager by showing that there are additional translations that allow one to use minimisation techniques in one semantic domain to obtain minimal representatives in the other semantic domain for these equivalences.

Dependability modeling and assessment in UML-based software development.

PubMed

Bernardi, Simona; Merseguer, José; Petriu, Dorina C

2012-01-01

Assessment of software nonfunctional properties (NFP) is an important problem in software development. In the context of model-driven development, an emerging approach for the analysis of different NFPs consists of the following steps: (a) to extend the software models with annotations describing the NFP of interest; (b) to transform automatically the annotated software model to the formalism chosen for NFP analysis; (c) to analyze the formal model using existing solvers; (d) to assess the software based on the results and give feedback to designers. Such a modeling→analysis→assessment approach can be applied to any software modeling language, be it general purpose or domain specific. In this paper, we focus on UML-based development and on the dependability NFP, which encompasses reliability, availability, safety, integrity, and maintainability. The paper presents the profile used to extend UML with dependability information, the model transformation to generate a DSPN formal model, and the assessment of the system properties based on the DSPN results.

Dependability Modeling and Assessment in UML-Based Software Development

PubMed Central

Bernardi, Simona; Merseguer, José; Petriu, Dorina C.

2012-01-01

Assessment of software nonfunctional properties (NFP) is an important problem in software development. In the context of model-driven development, an emerging approach for the analysis of different NFPs consists of the following steps: (a) to extend the software models with annotations describing the NFP of interest; (b) to transform automatically the annotated software model to the formalism chosen for NFP analysis; (c) to analyze the formal model using existing solvers; (d) to assess the software based on the results and give feedback to designers. Such a modeling→analysis→assessment approach can be applied to any software modeling language, be it general purpose or domain specific. In this paper, we focus on UML-based development and on the dependability NFP, which encompasses reliability, availability, safety, integrity, and maintainability. The paper presents the profile used to extend UML with dependability information, the model transformation to generate a DSPN formal model, and the assessment of the system properties based on the DSPN results. PMID:22988428

Dynamics of electronic transport in spatially-extended systems with negative differential conductivity

NASA Astrophysics Data System (ADS)

Xu, Huidong

Negative differential conductivity (NDC) is a nonlinear property of electronic transport for high electric field strength found in materials and devices such as semiconductor superlattices, bulk GaAs and Gunn diodes. In spatially extended systems, NDC can cause rich dynamics such as static and mobile field domains and moving charge fronts. In this thesis, these phenomena are studied theoretically and numerically for semiconductor superlattices. Two classes of models are considered: a discrete model based on sequential resonant tunneling between neighboring quantum wells is used to described charge transport in weakly-coupled superlattices, and a continuum model based on the miniband transport is used to describe charge transport strongly-coupled superlattices. The superlattice is a spatially extended nonlinear system consisting a periodic arrangement of quantum wells (e.g., GaAs) and barriers (e.g., AlAs). Using a discrete model and only considering one spatial dimension, we find that the boundary condition at the injecting contact has a great influence on the dynamical behavior for both fixed voltage and transient response. Static or moving field domains are usually inevitable in this system. In order to suppress field domains, we add a side shunting layer parallel to the growth direction of the superlattice. In this case, the model includes both vertical and lateral spatial degrees of freedom. We first study a shunted weakly-coupled superlattice for a wide range of material parameters. The field domains are found to be suppressed for superlattices with small lateral size and good connection between the shunt and the quantum wells of the superlattice. As the lateral size of the superlattice increases, the uniform field configuration loses its stability to either static or dynamic field domains, regardless of shunt properties. A lower quality shunt generally leads to regular and chaotic current oscillations and complex spatio-temporal dynamics in the field profile. Bifurcations separating static and dynamic behaviors are characterized and found to be dependent on the shunt properties. Then we adopt the model to study the shunted strongly-coupled superlattice with the continuum model. Key structural parameters associated with both the shunt layer and SL are identified for which the shunt layer stabilizes a uniform electric field profile. These results support the possibility to realize a SL-based THz oscillator with a carefully designed structure. Another important behavior of the static field domains in the weakly-coupled superlattice is bistability, i.e., two possible states (i.e., electric field configurations) for a single voltage. Noise can drive the system from one of these states (the metastable state) to the other one (the globally stable state). The process of escape from the metastable state can be viewed as a stochastic first-passage process in a high-dimensional system that possesses complex stability eigenvalues and for which a global potential energy function does not exist. This process is simulated using a stochastic differential equation system which incorporates shot noise. The mean switching time tau is fitted to an exponential expression e1DVth -Va, where Vth denotes the voltage at the end of the current branch. The exponent alpha in the fitting curve deviates from 1.5 which is predicted for a generic one dimensional system. We develop an algorithm to determine an effective locally valid potential. Principal component analysis is applied to find the most probable path for switching from the metastable current state.

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Numerical simulation of the generation, propagation, and diffraction of nonlinear waves in a rectangular basin: A three-dimensional numerical wave tank

NASA Astrophysics Data System (ADS)

Darwiche, Mahmoud Khalil M.

The research presented herein is a contribution to the understanding of the numerical modeling of fully nonlinear, transient water waves. The first part of the work involves the development of a time-domain model for the numerical generation of fully nonlinear, transient waves by a piston type wavemaker in a three-dimensional, finite, rectangular tank. A time-domain boundary-integral model is developed for simulating the evolving fluid field. A robust nonsingular, adaptive integration technique for the assembly of the boundary-integral coefficient matrix is developed and tested. A parametric finite-difference technique for calculating the fluid- particle kinematics is also developed and tested. A novel compatibility and continuity condition is implemented to minimize the effect of the singularities that are inherent at the intersections of the various Dirichlet and/or Neumann subsurfaces. Results are presented which demonstrate the accuracy and convergence of the numerical model. The second portion of the work is a study of the interaction of the numerically-generated, fully nonlinear, transient waves with a bottom-mounted, surface-piercing, vertical, circular cylinder. The numerical model developed in the first part of this dissertation is extended to include the presence of the cylinder at the centerline of the basin. The diffraction of the numerically generated waves by the cylinder is simulated, and the particle kinematics of the diffracted flow field are calculated and reported. Again, numerical results showing the accuracy and convergence of the extended model are presented.

Cooperativity and modularity in protein folding

PubMed Central

Sasai, Masaki; Chikenji, George; Terada, Tomoki P.

2016-01-01

A simple statistical mechanical model proposed by Wako and Saitô has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Muñoz and Eaton and has since been referred to as the Wako-Saitô-Muñoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saitô emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a native-like configuration and proceeds as growth and coalescence of these segments. The Φ-values calculated for barnase with the WSME model suggested that segments contributing to the folding nucleus are similar to the structural modules defined by the pattern of native atomic contacts. The WSME model was extended to explain folding of multi-domain proteins having a complex topology, which opened the way to comprehensively understanding the folding process of multi-domain proteins. The WSME model was also extended to describe allosteric transitions, indicating that the allosteric structural movement does not occur as a deterministic sequential change between two conformations but as a stochastic diffusive motion over the dynamically changing energy landscape. Statistical mechanical viewpoint on folding, as highlighted by the WSME model, has been renovated in the context of modern methods and ideas, and will continue to provide insights on equilibrium and dynamical features of proteins. PMID:28409080

Potts glass reflection of the decoding threshold for qudit quantum error correcting codes

NASA Astrophysics Data System (ADS)

Jiang, Yi; Kovalev, Alexey A.; Pryadko, Leonid P.

We map the maximum likelihood decoding threshold for qudit quantum error correcting codes to the multicritical point in generalized Potts gauge glass models, extending the map constructed previously for qubit codes. An n-qudit quantum LDPC code, where a qudit can be involved in up to m stabilizer generators, corresponds to a ℤd Potts model with n interaction terms which can couple up to m spins each. We analyze general properties of the phase diagram of the constructed model, give several bounds on the location of the transitions, bounds on the energy density of extended defects (non-local analogs of domain walls), and discuss the correlation functions which can be used to distinguish different phases in the original and the dual models. This research was supported in part by the Grants: NSF PHY-1415600 (AAK), NSF PHY-1416578 (LPP), and ARO W911NF-14-1-0272 (LPP).

Interdependence of the rad50 hook and globular domain functions.

PubMed

Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

2015-02-05

Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Domain wall assisted GMR head with spin-Hall effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arun, R., E-mail: arunbdu@gmail.com; Sabareesan, P., E-mail: sendtosabari@gmail.com; Daniel, M., E-mail: danielcnld@gmail.com

2016-05-06

We theoretically study the dynamics of a field induced domain wall in the Py/Pt bi-layer structure in the presence of spin-Hall effect (SHE) by solving the Landau-Lifshitz-Gilbert (LLG) equation along with the adiabatic, nonadiabatic and SHE spin-transfer torques (STTs). It is observed that a weak magnetic field moves the domain wall with high velocity in the presence of SHE and the direction of the velocity is changed by changing the direction of the weak field. The numerical results show that the magnetization of the ferromagnetic layer can be reversed quickly through domain wall motion by changing the direction of amore » weak external field in the presence of SHE while the direction of current is fixed. The SHE reduces the magnetization reversal time of 1000 nm length strip by 14.7 ns. This study is extended to model a domain wall based GMR (Giant Magnetoresistance) read head with SHE.« less

Generating Dynamic Persistence in the Time Domain

NASA Astrophysics Data System (ADS)

Guerrero, A.; Smith, L. A.; Smith, L. A.; Kaplan, D. T.

2001-12-01

Many dynamical systems present long-range correlations. Physically, these systems vary from biological to economical, including geological or urban systems. Important geophysical candidates for this type of behaviour include weather (or climate) and earthquake sequences. Persistence is characterised by slowly decaying correlation function; that, in theory, never dies out. The Persistence exponent reflects the degree of memory in the system and much effort has been expended creating and analysing methods that successfully estimate this parameter and model data that exhibits persistence. The most widely used methods for generating long correlated time series are not dynamical systems in the time domain, but instead are derived from a given spectral density. Little attention has been drawn to modelling persistence in the time domain. The time domain approach has the advantage that an observation at certain time can be calculated using previous observations which is particularly suitable when investigating the predictability of a long memory process. We will describe two of these methods in the time domain. One is a traditional approach using fractional ARIMA (autoregressive and moving average) models; the second uses a novel approach to extending a given series using random Fourier basis functions. The statistical quality of the two methods is compared, and they are contrasted with weather data which shows, reportedly, persistence. The suitability of this approach both for estimating predictability and for making predictions is discussed.

A UML profile for the OBO relation ontology

PubMed Central

2012-01-01

Background Ontologies have increasingly been used in the biomedical domain, which has prompted the emergence of different initiatives to facilitate their development and integration. The Open Biological and Biomedical Ontologies (OBO) Foundry consortium provides a repository of life-science ontologies, which are developed according to a set of shared principles. This consortium has developed an ontology called OBO Relation Ontology aiming at standardizing the different types of biological entity classes and associated relationships. Since ontologies are primarily intended to be used by humans, the use of graphical notations for ontology development facilitates the capture, comprehension and communication of knowledge between its users. However, OBO Foundry ontologies are captured and represented basically using text-based notations. The Unified Modeling Language (UML) provides a standard and widely-used graphical notation for modeling computer systems. UML provides a well-defined set of modeling elements, which can be extended using a built-in extension mechanism named Profile. Thus, this work aims at developing a UML profile for the OBO Relation Ontology to provide a domain-specific set of modeling elements that can be used to create standard UML-based ontologies in the biomedical domain. Results We have studied the OBO Relation Ontology, the UML metamodel and the UML profiling mechanism. Based on these studies, we have proposed an extension to the UML metamodel in conformance with the OBO Relation Ontology and we have defined a profile that implements the extended metamodel. Finally, we have applied the proposed UML profile in the development of a number of fragments from different ontologies. Particularly, we have considered the Gene Ontology (GO), the PRotein Ontology (PRO) and the Xenopus Anatomy and Development Ontology (XAO). Conclusions The use of an established and well-known graphical language in the development of biomedical ontologies provides a more intuitive form of capturing and representing knowledge than using only text-based notations. The use of the profile requires the domain expert to reason about the underlying semantics of the concepts and relationships being modeled, which helps preventing the introduction of inconsistencies in an ontology under development and facilitates the identification and correction of errors in an already defined ontology. PMID:23095840

Dynamic imaging in electrical impedance tomography of the human chest with online transition matrix identification.

PubMed

Moura, Fernando Silva; Aya, Julio Cesar Ceballos; Fleury, Agenor Toledo; Amato, Marcelo Britto Passos; Lima, Raul Gonzalez

2010-02-01

One of the electrical impedance tomography objectives is to estimate the electrical resistivity distribution in a domain based only on electrical potential measurements at its boundary generated by an imposed electrical current distribution into the boundary. One of the methods used in dynamic estimation is the Kalman filter. In biomedical applications, the random walk model is frequently used as evolution model and, under this conditions, poor tracking ability of the extended Kalman filter (EKF) is achieved. An analytically developed evolution model is not feasible at this moment. The paper investigates the identification of the evolution model in parallel to the EKF and updating the evolution model with certain periodicity. The evolution model transition matrix is identified using the history of the estimated resistivity distribution obtained by a sensitivity matrix based algorithm and a Newton-Raphson algorithm. To numerically identify the linear evolution model, the Ibrahim time-domain method is used. The investigation is performed by numerical simulations of a domain with time-varying resistivity and by experimental data collected from the boundary of a human chest during normal breathing. The obtained dynamic resistivity values lie within the expected values for the tissues of a human chest. The EKF results suggest that the tracking ability is significantly improved with this approach.

Influence of spin creepage and contact angle on curve squeal: A numerical approach

NASA Astrophysics Data System (ADS)

Zenzerovic, I.; Kropp, W.; Pieringer, A.

2018-04-01

Curve squeal is a loud tonal sound that may arise when a railway vehicle negotiates a tight curve. Due to the nonlinear nature of squeal, time-domain models provide a higher degree of accuracy in comparison to frequency-domain models and also enable the determination of squeal amplitudes. In the present paper, a previously developed engineering time-domain model for curve squeal is extended to include the effects of the contact angle and spin creepage. The extensions enable the evaluation of more realistic squeal cases with the computationally efficient model. The model validation against Kalker's variational contact model shows good agreement between the models. Results of studies on the influence of spin creepage and contact angle show that the contact angle has a significant influence on the vertical-lateral dynamics coupling and, therefore, influences both squeal amplitude and frequency. Spin creepage mainly influences processes in the contact, therefore influencing the tangential contact force amplitude. In the combined spin-contact angle study the spin creepage value is kinematically related to the contact angle value. Results indicate that the influence of the contact angle is dominant over the influence of spin creepage. In general, results indicate that the most crucial factors in squeal are those that influence the dynamics coupling: the contact angle, wheel/rail contact positions and friction.

An Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model

PubMed Central

Harjes, Elena; Gross, Phillip J.; Chen, Kuan-Ming; Lu, Yongjian; Shindo, Keisuke; Nowarski, Roni; Gross, John D.; Kotler, Moshe; Harris, Reuben S.; Matsuo, Hiroshi

2009-01-01

Summary Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases. This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA, respectively. A3G deaminates cytidines to uridines in single-strand DNA and inhibits the replication of HIV-1, other retroviruses and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has been investigated genetically and biochemically, atomic details are just starting to emerge. Here, we compare the DNA cytidine deaminase activities and NMR structures of two A3G catalytic domain constructs. The longer A3G191-384 protein is considerably more active than the shorter A3G198-384 variant. The longer structure has an α1 helix (residues 201–206) that was not apparent in the shorter protein and it contributes to catalytic activity through interactions with hydrophobic core structures (β1, β3, α5 and α6). Both A3G catalytic domain solution structures have a discontinuous β2 region that is clearly different than the continuous β2 strand of another family member APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N-terminal pseudo-catalytic domain including the inter-domain linker and some of the last α-helix. These structured residues (191–196) enabled a novel full-length A3G model by providing physical overlap between the N-terminal pseudo-catalytic domain and the new C-terminal catalytic domain structure. Contrary to predictions, this structurally constrained model suggested that the two domains are tethered by structured residues and that the N- and C-terminal β2 regions are too distant from one another to participate in this interaction. PMID:19389408

Saturation of the magnetorotational instability in the unstratified shearing box with zero net flux: convergence in taller boxes

NASA Astrophysics Data System (ADS)

Shi, Ji-Ming; Stone, James M.; Huang, Chelsea X.

2016-03-01

Previous studies of the non-linear regime of the magnetorotational instability in one particular type of shearing box model - unstratified with no net magnetic flux - find that without explicit dissipation (viscosity and resistivity) the saturation amplitude decreases with increasing numerical resolution. We show that this result is strongly dependent on the vertical aspect ratio of the computational domain Lz/Lx. When Lz/Lx ≲ 1, we recover previous results. However, when the vertical domain is extended Lz/Lx ≳ 2.5, we find the saturation level of the stress is greatly increased (giving a ratio of stress to pressure α ≳ 0.1), and moreover the results are independent of numerical resolution. Consistent with previous results, we find that saturation of the magnetorotational (MRI) in this regime is controlled by a cyclic dynamo which generates patches of strong toroidal field that switches sign on scales of Lx in the vertical direction. We speculate that when Lz/Lx ≲ 1, the dynamo is inhibited by the small size of the vertical domain, leading to the puzzling dependence of saturation amplitude on resolution. We show that previous toy models developed to explain the MRI dynamo are consistent with our results, and that the cyclic pattern of toroidal fields observed in stratified shearing box simulations (leading to the so-called butterfly diagram) may also be related. In tall boxes the saturation amplitude is insensitive to whether or not explicit dissipation is included in the calculations, at least for large magnetic Reynolds and Prandtl number. Finally, we show MRI turbulence in tall domains has a smaller critical Pmc, and an extended lifetime compared to Lz/Lx ≲ 1 boxes.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

PubMed Central

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-01-01

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001 PMID:28695824

Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains?

PubMed

Erickson, Harold P

2017-02-01

Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. FNIII domains should therefore not be unfolded until the tension approaches 5pN. Integrins have been reported to generate forces ranging from 1 to >50pN, but I argue that studies reporting 1-2pN are the most convincing. This is not enough to unfold FNIII domains. Even if domains were unfolded, 2pN would only extend the worm-like-chain to about twice the length of the folded domain. Overall I conclude that stretching FN matrix fibrils involves primarily the compact to extended conformational change of FN dimers, with minimal contribution from unfolding FNIII domains. Copyright © 2016 Elsevier Ltd. All rights reserved.

A flexible, extendable, modular and computationally efficient approach to scattering-integral-based seismic full waveform inversion

NASA Astrophysics Data System (ADS)

Schumacher, F.; Friederich, W.; Lamara, S.

2016-02-01

We present a new conceptual approach to scattering-integral-based seismic full waveform inversion (FWI) that allows a flexible, extendable, modular and both computationally and storage-efficient numerical implementation. To achieve maximum modularity and extendability, interactions between the three fundamental steps carried out sequentially in each iteration of the inversion procedure, namely, solving the forward problem, computing waveform sensitivity kernels and deriving a model update, are kept at an absolute minimum and are implemented by dedicated interfaces. To realize storage efficiency and maximum flexibility, the spatial discretization of the inverted earth model is allowed to be completely independent of the spatial discretization employed by the forward solver. For computational efficiency reasons, the inversion is done in the frequency domain. The benefits of our approach are as follows: (1) Each of the three stages of an iteration is realized by a stand-alone software program. In this way, we avoid the monolithic, unflexible and hard-to-modify codes that have often been written for solving inverse problems. (2) The solution of the forward problem, required for kernel computation, can be obtained by any wave propagation modelling code giving users maximum flexibility in choosing the forward modelling method. Both time-domain and frequency-domain approaches can be used. (3) Forward solvers typically demand spatial discretizations that are significantly denser than actually desired for the inverted model. Exploiting this fact by pre-integrating the kernels allows a dramatic reduction of disk space and makes kernel storage feasible. No assumptions are made on the spatial discretization scheme employed by the forward solver. (4) In addition, working in the frequency domain effectively reduces the amount of data, the number of kernels to be computed and the number of equations to be solved. (5) Updating the model by solving a large equation system can be done using different mathematical approaches. Since kernels are stored on disk, it can be repeated many times for different regularization parameters without need to solve the forward problem, making the approach accessible to Occam's method. Changes of choice of misfit functional, weighting of data and selection of data subsets are still possible at this stage. We have coded our approach to FWI into a program package called ASKI (Analysis of Sensitivity and Kernel Inversion) which can be applied to inverse problems at various spatial scales in both Cartesian and spherical geometries. It is written in modern FORTRAN language using object-oriented concepts that reflect the modular structure of the inversion procedure. We validate our FWI method by a small-scale synthetic study and present first results of its application to high-quality seismological data acquired in the southern Aegean.

Polar Domain Discovery with Sparkler

NASA Astrophysics Data System (ADS)

Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

2017-12-01

The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

Numerical models for fluid-grains interactions: opportunities and limitations

NASA Astrophysics Data System (ADS)

Esteghamatian, Amir; Rahmani, Mona; Wachs, Anthony

2017-06-01

In the framework of a multi-scale approach, we develop numerical models for suspension flows. At the micro scale level, we perform particle-resolved numerical simulations using a Distributed Lagrange Multiplier/Fictitious Domain approach. At the meso scale level, we use a two-way Euler/Lagrange approach with a Gaussian filtering kernel to model fluid-solid momentum transfer. At both the micro and meso scale levels, particles are individually tracked in a Lagrangian way and all inter-particle collisions are computed by a Discrete Element/Soft-sphere method. The previous numerical models have been extended to handle particles of arbitrary shape (non-spherical, angular and even non-convex) as well as to treat heat and mass transfer. All simulation tools are fully-MPI parallel with standard domain decomposition and run on supercomputers with a satisfactory scalability on up to a few thousands of cores. The main asset of multi scale analysis is the ability to extend our comprehension of the dynamics of suspension flows based on the knowledge acquired from the high-fidelity micro scale simulations and to use that knowledge to improve the meso scale model. We illustrate how we can benefit from this strategy for a fluidized bed, where we introduce a stochastic drag force model derived from micro-scale simulations to recover the proper level of particle fluctuations. Conversely, we discuss the limitations of such modelling tools such as their limited ability to capture lubrication forces and boundary layers in highly inertial flows. We suggest ways to overcome these limitations in order to enhance further the capabilities of the numerical models.

Estimating the Return of Higher Education in Algeria: Evidence from Adrar University

ERIC Educational Resources Information Center

Houcine, Benlaria; Sofiane, Mostéfaoui

2018-01-01

This study aims to measure the individual rate of return for investment in higher education at Adrar University by using both basic and extended Mincerian Earnings Function. In addition to this, the comparison had been established between the results obtained and those of other researches in the same domain. We adopted in the research the model of…

Dimers in Piecewise Temperleyan Domains

NASA Astrophysics Data System (ADS)

Russkikh, Marianna

2018-03-01

We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

U14 small nucleolar RNA makes multiple contacts with the pre-ribosomal RNA.

PubMed

Morrissey, J P; Tollervey, D

1997-06-01

The small nucleolar RNA (snoRNA) U14 has two regions of extended primary sequence complementarity to the 18S rRNA. The 3' region (domain B) shows the consensus structure for the methylation guide class of snoRNAs, whereas base-pairing between the 5' region (domain A) and the 18S rRNA sequence is required for the formation of functional ribosomes. Between domains A and B lies another essential region (domain Y). Here we report that yeast U14 can be cross-linked in vivo to the pre-rRNA; cross-linking is detected exclusively with the 35S primary transcript. Many nucleotides in U14 that lie outside of domains A and B are cross-linked to the pre-rRNA; in particular the essential domain Y region is cross-linked at several sites. U14 is, therefore, in far more extensive contact with the pre-rRNA than predicted from simple base-pairing models. Moreover, U14 can be cross-linked to other small RNA species. The functional interactions made by U14 during ribosome synthesis are likely to be very complex.

Ratchet Effects and Domain Wall Energy Landscapes in Amorphous Magnetic Films with 2D Arrays of Asymmetric Holes

NASA Astrophysics Data System (ADS)

Martin, J. I.; Alija, A.; Sobrado, I.; Perez-Junquera, A.; Rodriguez-Rodriguez, G.; Velez, M.; Alameda, J. M.; Marconi, V. I.; Kolton, A. B.; Parrondo, J. M. R.

2009-03-01

The driven motion of domain walls in extended magnetic films patterned with 2D arrays of asymmetric holes has been found to be subject to two different crossed ratchet effects [1] which results in an inversion of the sign of domain wall motion rectification as a function of the applied magnetic field. This effect can be understood in terms of the competition between drive, elasticity and asymmetric pinning as revealed by a simple 4̂-model. In order to optimize the asymmetric hole design, the relevant energy landscapes for domain wall motion across the array of asymmetric holes have been calculated by micromagnetic simulations as a function of array geometrical characteristics. The effects of a transverse magnetic field on these two crossed ratchet effects will also be discussed in terms of the decrease in domain wall energy per unit area and of the modifications in the magnetostatic barriers for domain wall pinning at the asymmetric inclusions. Work supported by Spanish MICINN.[1] A. Perez-Junquera et al, Phys. Rev. Lett. 100 (2008) 037203

MOCASSIN-prot: a multi-objective clustering approach for protein similarity networks.

PubMed

Keel, Brittney N; Deng, Bo; Moriyama, Etsuko N

2018-04-15

Proteins often include multiple conserved domains. Various evolutionary events including duplication and loss of domains, domain shuffling, as well as sequence divergence contribute to generating complexities in protein structures, and consequently, in their functions. The evolutionary history of proteins is hence best modeled through networks that incorporate information both from the sequence divergence and the domain content. Here, a game-theoretic approach proposed for protein network construction is adapted into the framework of multi-objective optimization, and extended to incorporate clustering refinement procedure. The new method, MOCASSIN-prot, was applied to cluster multi-domain proteins from ten genomes. The performance of MOCASSIN-prot was compared against two protein clustering methods, Markov clustering (TRIBE-MCL) and spectral clustering (SCPS). We showed that compared to these two methods, MOCASSIN-prot, which uses both domain composition and quantitative sequence similarity information, generates fewer false positives. It achieves more functionally coherent protein clusters and better differentiates protein families. MOCASSIN-prot, implemented in Perl and Matlab, is freely available at http://bioinfolab.unl.edu/emlab/MOCASSINprot. emoriyama2@unl.edu. Supplementary data are available at Bioinformatics online.

Orientation of Myosin Binding Protein C in the Cardiac Muscle Sarcomere Determined by Domain-Specific Immuno-EM

PubMed Central

Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger

2014-01-01

Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032

Overview of the GRC Stirling Convertor System Dynamic Model

NASA Technical Reports Server (NTRS)

Lewandowski, Edward J.; Regan, Timothy F.

2004-01-01

A Stirling Convertor System Dynamic Model has been developed at the Glenn Research Center for controls, dynamics, and systems development of free-piston convertor power systems. It models the Stirling cycle thermodynamics, heat flow, gas, mechanical, and mounting dynamics, the linear alternator, and the controller. The model's scope extends from the thermal energy input to thermal, mechanical dynamics, and electrical energy out, allowing one to study complex system interactions among subsystems. The model is a non-linear time-domain model containing sub-cycle dynamics, allowing it to simulate transient and dynamic phenomena that other models cannot. The model details and capability are discussed.

Planning, Anticipatory Systems, and Kinds of Actors

NASA Astrophysics Data System (ADS)

Jorna, René; van Wezel, Wout

2002-09-01

Anticipation and planning have much in common. Anticipation means being ahead of things. Planning means not only anticipating on things to come, but also trying to determine a course of action to reach a goal. Planning is investigated in many domains, for example, in economy, biology, and in the cognitive sciences. Each of these domains uses its own research methodologies, languages, ontologies, and models. Although there are many differences between the various approaches and models, there must of course also be similarities, since they all deal with establishing a future course of actions to reach a goal. We will compare several planning approaches on a number of aspects, e.g., the kind of entity that makes the plan (natural or artificial), whether the plan is executed by the planner or by another entity, representational issues, and the domain that the plan is executed in. Our article focuses on analytical dimensions in the extended field of planning. We do not discuss empirical results.

Toward domain-specific design environments: Some representation ideas from the telecommunications domain

NASA Technical Reports Server (NTRS)

Greenspan, Sol; Feblowitz, Mark

1992-01-01

ACME is an experimental environment for investigating new approaches to modeling and analysis of system requirements and designs. ACME is built on and extends object-oriented conceptual modeling techniques and knowledge representation and reasoning (KRR) tools. The most immediate intended use for ACME is to help represent, understand, and communicate system designs during the early stages of system planning and requirements engineering. While our research is ostensibly aimed at software systems in general, we are particularly motivated to make an impact in the telecommunications domain, especially in the area referred to as Intelligent Networks (IN's). IN systems contain the software to provide services to users of a telecommunications network (e.g., call processing services, information services, etc.) as well as the software that provides the internal infrastructure for providing the services (e.g., resource management, billing, etc.). The software includes not only systems developed by the network proprietors but also by a growing group of independent service software providers.

Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.

PubMed

Isaac, R E; Michaud, A; Keen, J N; Williams, T A; Coates, D; Wetsel, W C; Corvol, P

1999-06-01

Endoproteolytic cleavage of protein prohormones often generates intermediates extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a carboxypeptidase (CPE) is normally an important step in the maturation of many peptide hormones. Recent studies in mice that lack CP activity indicate the existence of alternative tissue or plasma enzymes capable of removing C-terminal basic residues from prohormone intermediates. Using inhibitors of angiotensin I-converting enzyme (ACE) and CP, we show that both these enzymes in mouse serum can remove the basic amino acids from the C-terminus of CCK5-GRR and LH-RH-GKR, but only CP is responsible for converting diarginyl insulin to insulin. ACE activity removes C-terminal dipeptides to generate the Gly-extended peptides, whereas CP hydrolysis gives rise to CCK5-GR and LH-RH-GK, both of which are susceptible to the dipeptidyl carboxypeptidase activity of ACE. Somatic ACE has two similar protein domains (the N-domain and the C-domain), each with an active site that can display different substrate specificities. CCK5-GRR is a high-affinity substrate for both the N-domain and C-domain active sites of human sACE (Km of 9.4 microm and 9.0 microm, respectively) with the N-domain showing greater efficiency (kcat : Km ratio of 2.6 in favour of the N-domain). We conclude that somatic forms of ACE should be considered as alternatives to CPs for the removal of basic residues from some Arg/Lys-extended peptides.

Coupling MHD and PIC models in 2 dimensions

NASA Astrophysics Data System (ADS)

Daldorff, L.; Toth, G.; Sokolov, I.; Gombosi, T. I.; Lapenta, G.; Brackbill, J. U.; Markidis, S.; Amaya, J.

2013-12-01

Even for extended fluid plasma models, like Hall, anisotropic ion pressure and multi fluid MHD, there are still many plasma phenomena that are not well captured. For this reason, we have coupled the Implicit Particle-In-Cell (iPIC3D) code with the BATSRUS global MHD code. The PIC solver is applied in a part of the computational domain, for example, in the vicinity of reconnection sites, and overwrites the MHD solution. On the other hand, the fluid solver provides the boundary conditions for the PIC code. To demonstrate the use of the coupled codes for magnetospheric applications, we perform a 2D magnetosphere simulation, where BATSRUS solves for Hall MHD in the whole domain except for the tail reconnection region, which is handled by iPIC3D.

Circuit transients due to negative bias arcs-II. [on solar cell power systems in low earth orbit

NASA Technical Reports Server (NTRS)

Metz, R. N.

1986-01-01

Two new models of negative-bias arcing on a solar cell power system in Low Earth Orbit are presented. One is an extended, analytical model and the other is a non-linear, numerical model. The models are based on an earlier analytical model in which the interactions between solar cell interconnects and the space plasma as well as the parameters of the power circuit are approximated linearly. Transient voltages due to arcs struck at the negative thermal of the solar panel are calculated in the time domain. The new models treat, respectively, further linear effects within the solar panel load circuit and non-linear effects associated with the plasma interactions. Results of computer calculations with the models show common-mode voltage transients of the electrically floating solar panel struck by an arc comparable to the early model but load transients that differ substantially from the early model. In particular, load transients of the non-linear model can be more than twice as great as those of the early model and more than twenty times as great as the extended, linear model.

Analytical formulation of 2-D aeroelastic model in weak ground effect

NASA Astrophysics Data System (ADS)

Dessi, Daniele; Mastroddi, Franco; Mancini, Simone

2013-10-01

This paper deals with the aeroelastic modeling and analysis of a 2-D oscillating airfoil in ground effect, elastically constrained by linear and torsional springs and immersed in an incompressible potential flow (typical section) at a finite distance from the ground. This work aims to extend Theodorsen theory, valid in an unbounded flow domain, to the case of weak ground effect, i.e., for clearances above half the airfoil chord. The key point is the determination of the aerodynamic loads, first in the frequency domain and then in the time domain, accounting for their dependence on the ground distance. The method of images is exploited in order to comply with the impermeability condition on the ground. The new integral equation in the unknown vortex distribution along the chord and the wake is solved using asymptotic expansions in the perturbation parameter defined as the inverse of the non-dimensional ground clearance of the airfoil. The mathematical model describing the aeroelastic system is transformed from the frequency domain into the time domain and then in a pure differential form using a finite-state aerodynamic approximation (augmented states). The typical section, which the developed theory is applied to, is obtained as a reduced model of a wing box finite element representation, thus allowing comparison with the corresponding aeroelastic analysis carried out by a commercial solver based on a 3-D lifting surface aerodynamic model. Stability (flutter margins) and response of the airfoil both in frequency and time domains are then investigated. In particular, within the developed theory, the solution of the Wagner problem can be directly achieved confirming an asymptotic trend of the aerodynamic coefficients toward the steady-state conditions different from that relative to the unbounded domain case. The dependence of flutter speed and the frequency response functions on ground clearance is highlighted, showing the usefulness of this approach in efficiently and robustly accounting for the presence of the ground when unsteady analysis of elastic lifting surfaces in weak ground effect is required.

Homeopathic potentization based on nanoscale domains.

PubMed

Czerlinski, George; Ypma, Tjalling

2011-12-01

The objectives of this study were to present a simple descriptive and quantitative model of how high potencies in homeopathy arise. The model begins with the mechanochemical production of hydrogen and hydroxyl radicals from water and the electronic stabilization of the resulting nanodomains of water molecules. The life of these domains is initially limited to a few days, but may extend to years when the electromagnetic characteristic of a homeopathic agent is copied onto the domains. This information is transferred between the original agent and the nanodomains, and also between previously imprinted nanodomains and new ones. The differential equations previously used to describe these processes are replaced here by exponential expressions, corresponding to simplified model mechanisms. Magnetic stabilization is also involved, since these long-lived domains apparently require the presence of the geomagnetic field. Our model incorporates this factor in the formation of the long-lived compound. Numerical simulation and graphs show that the potentization mechanism can be described quantitatively by a very simplified mechanism. The omitted factors affect only the fine structure of the kinetics. Measurements of pH changes upon absorption of different electromagnetic frequencies indicate that about 400 nanodomains polymerize to form one cooperating unit. Singlet excited states of some compounds lead to dramatic changes in their hydrogen ion dissociation constant, explaining this pH effect and suggesting that homeopathic information is imprinted as higher singlet excited states. A simple description is provided of the process of potentization in homeopathic dilutions. With the exception of minor details, this simple model replicates the results previously obtained from a more complex model. While excited states are short lived in isolated molecules, they become long lived in nanodomains that form coherent cooperative aggregates controlled by the geomagnetic field. These domains either slowly emit biophotons or perform specific biochemical work at their target.

Extended Bose Hubbard model of interacting bosonic atoms in optical lattices: From superfluidity to density waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazzarella, G.; Giampaolo, S. M.; Illuminati, F.

2006-01-15

For systems of interacting, ultracold spin-zero neutral bosonic atoms, harmonically trapped and subject to an optical lattice potential, we derive an Extended Bose Hubbard (EBH) model by developing a systematic expansion for the Hamiltonian of the system in powers of the lattice parameters and of a scale parameter, the lattice attenuation factor. We identify the dominant terms that need to be retained in realistic experimental conditions, up to nearest-neighbor interactions and nearest-neighbor hoppings conditioned by the on-site occupation numbers. In the mean field approximation, we determine the free energy of the system and study the phase diagram both at zeromore » and at finite temperature. At variance with the standard on site Bose Hubbard model, the zero-temperature phase diagram of the EBH model possesses a dual structure in the Mott insulating regime. Namely, for specific ranges of the lattice parameters, a density wave phase characterizes the system at integer fillings, with domains of alternating mean occupation numbers that are the atomic counterparts of the domains of staggered magnetizations in an antiferromagnetic phase. We show as well that in the EBH model, a zero-temperature quantum phase transition to pair superfluidity is, in principle, possible, but completely suppressed at the lowest order in the lattice attenuation factor. Finally, we determine the possible occurrence of the different phases as a function of the experimentally controllable lattice parameters.« less

Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan.

PubMed

Schanda, Paul; Triboulet, Sébastien; Laguri, Cédric; Bougault, Catherine M; Ayala, Isabel; Callon, Morgane; Arthur, Michel; Simorre, Jean-Pierre

2014-12-24

The maintenance of bacterial cell shape and integrity is largely attributed to peptidoglycan, a highly cross-linked biopolymer. The transpeptidases that perform this cross-linking are important targets for antibiotics. Despite this biomedical importance, to date no structure of a protein in complex with an intact bacterial peptidoglycan has been resolved, primarily due to the large size and flexibility of peptidoglycan sacculi. Here we use solid-state NMR spectroscopy to derive for the first time an atomic model of an l,d-transpeptidase from Bacillus subtilis bound to its natural substrate, the intact B. subtilis peptidoglycan. Importantly, the model obtained from protein chemical shift perturbation data shows that both domains-the catalytic domain as well as the proposed peptidoglycan recognition domain-are important for the interaction and reveals a novel binding motif that involves residues outside of the classical enzymatic pocket. Experiments on mutants and truncated protein constructs independently confirm the binding site and the implication of both domains. Through measurements of dipolar-coupling derived order parameters of bond motion we show that protein binding reduces the flexibility of peptidoglycan. This first report of an atomic model of a protein-peptidoglycan complex paves the way for the design of new antibiotic drugs targeting l,d-transpeptidases. The strategy developed here can be extended to the study of a large variety of enzymes involved in peptidoglycan morphogenesis.

Bioconvection in spatially extended domains

NASA Astrophysics Data System (ADS)

Karimi, A.; Paul, M. R.

2013-05-01

We numerically explore gyrotactic bioconvection in large spatially extended domains of finite depth using parameter values from available experiments with the unicellular alga Chlamydomonas nivalis. We numerically integrate the three-dimensional, time-dependent continuum model of Pedley [J. Fluid Mech.10.1017/S0022112088002393 195, 223 (1988)] using a high-order, parallel, spectral-element approach. We explore the long-time nonlinear patterns and dynamics found for layers with an aspect ratio of 10 over a range of Rayleigh numbers. Our results yield the pattern wavelength and pattern dynamics which we compare with available theory and experimental measurement. There is good agreement for the pattern wavelength at short times between numerics, experiment, and a linear stability analysis. At long times we find that the general sequence of patterns given by the nonlinear evolution of the governing equations correspond qualitatively to what has been described experimentally. However, at long times the patterns in numerics grow to larger wavelengths, in contrast to what is observed in experiment where the wavelength is found to decrease with time.

Transcription initiation complex structures elucidate DNA opening.

PubMed

Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

2016-05-19

Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

Scalable Parallel Computation for Extended MHD Modeling of Fusion Plasmas

NASA Astrophysics Data System (ADS)

Glasser, Alan H.

2008-11-01

Parallel solution of a linear system is scalable if simultaneously doubling the number of dependent variables and the number of processors results in little or no increase in the computation time to solution. Two approaches have this property for parabolic systems: multigrid and domain decomposition. Since extended MHD is primarily a hyperbolic rather than a parabolic system, additional steps must be taken to parabolize the linear system to be solved by such a method. Such physics-based preconditioning (PBP) methods have been pioneered by Chac'on, using finite volumes for spatial discretization, multigrid for solution of the preconditioning equations, and matrix-free Newton-Krylov methods for the accurate solution of the full nonlinear preconditioned equations. The work described here is an extension of these methods using high-order spectral element methods and FETI-DP domain decomposition. Application of PBP to a flux-source representation of the physics equations is discussed. The resulting scalability will be demonstrated for simple wave and for ideal and Hall MHD waves.

A Kernel Embedding-Based Approach for Nonstationary Causal Model Inference.

PubMed

Hu, Shoubo; Chen, Zhitang; Chan, Laiwan

2018-05-01

Although nonstationary data are more common in the real world, most existing causal discovery methods do not take nonstationarity into consideration. In this letter, we propose a kernel embedding-based approach, ENCI, for nonstationary causal model inference where data are collected from multiple domains with varying distributions. In ENCI, we transform the complicated relation of a cause-effect pair into a linear model of variables of which observations correspond to the kernel embeddings of the cause-and-effect distributions in different domains. In this way, we are able to estimate the causal direction by exploiting the causal asymmetry of the transformed linear model. Furthermore, we extend ENCI to causal graph discovery for multiple variables by transforming the relations among them into a linear nongaussian acyclic model. We show that by exploiting the nonstationarity of distributions, both cause-effect pairs and two kinds of causal graphs are identifiable under mild conditions. Experiments on synthetic and real-world data are conducted to justify the efficacy of ENCI over major existing methods.

A Stochastic Climate Generator for Agriculture in Southeast Asian Domains

NASA Astrophysics Data System (ADS)

Greene, A. M.; Allis, E. C.

2014-12-01

We extend a previously-described method for generating future climate scenarios, suitable for driving agricultural models, to selected domains in Lao PDR, Bangladesh and Indonesia. There are notable differences in climatology among the study regions, most importantly the inverse seasonal relationship of southeast Asian and Australian monsoons. These differences necessitate a partially-differentiated modeling approach, utilizing common features for better estimation while allowing independent modeling of divergent attributes. The method attempts to constrain uncertainty due to both anthropogenic and natural influences, providing a measure of how these effects may combine during specified future decades. Seasonal climate fields are downscaled to the daily time step by resampling the AgMERRA dataset, providing a full suite of agriculturally relevant variables and enabling the propagation of climate uncertainty to agricultural outputs. The role of this research in a broader project, conducted under the auspices of the International Fund for Agricultural Development (IFAD), is discussed.

Structure and Function of the Intracellular Region of the Plexin-B1 Transmembrane Receptor*

PubMed Central

Tong, Yufeng; Hota, Prasanta K.; Penachioni, Junia Y.; Hamaneh, Mehdi B.; Kim, SoonJeung; Alviani, Rebecca S.; Shen, Limin; He, Hao; Tempel, Wolfram; Tamagnone, Luca; Park, Hee-Won; Buck, Matthias

2009-01-01

Members of the plexin family are unique transmembrane receptors in that they interact directly with Rho family small GTPases; moreover, they contain a GTPase-activating protein (GAP) domain for R-Ras, which is crucial for plexin-mediated regulation of cell motility. However, the functional role and structural basis of the interactions between the different intracellular domains of plexins remained unclear. Here we present the 2.4 Å crystal structure of the complete intracellular region of human plexin-B1. The structure is monomeric and reveals that the GAP domain is folded into one structure from two segments, separated by the Rho GTPase binding domain (RBD). The RBD is not dimerized, as observed previously. Instead, binding of a conserved loop region appears to compete with dimerization and anchors the RBD to the GAP domain. Cell-based assays on mutant proteins confirm the functional importance of this coupling loop. Molecular modeling based on structural homology to p120GAP·H-Ras suggests that Ras GTPases can bind to the plexin GAP region. Experimentally, we show that the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation. PMID:19843518

Modular System for Shelves and Coasts (MOSSCO v1.0) - a flexible and multi-component framework for coupled coastal ocean ecosystem modelling

NASA Astrophysics Data System (ADS)

Lemmen, Carsten; Hofmeister, Richard; Klingbeil, Knut; Hassan Nasermoaddeli, M.; Kerimoglu, Onur; Burchard, Hans; Kösters, Frank; Wirtz, Kai W.

2018-03-01

Shelf and coastal sea processes extend from the atmosphere through the water column and into the seabed. These processes reflect intimate interactions between physical, chemical, and biological states on multiple scales. As a consequence, coastal system modelling requires a high and flexible degree of process and domain integration; this has so far hardly been achieved by current model systems. The lack of modularity and flexibility in integrated models hinders the exchange of data and model components and has historically imposed the supremacy of specific physical driver models. We present the Modular System for Shelves and Coasts (MOSSCO; http://www.mossco.de), a novel domain and process coupling system tailored but not limited to the coupling challenges of and applications in the coastal ocean. MOSSCO builds on the Earth System Modeling Framework (ESMF) and on the Framework for Aquatic Biogeochemical Models (FABM). It goes beyond existing technologies by creating a unique level of modularity in both domain and process coupling, including a clear separation of component and basic model interfaces, flexible scheduling of several tens of models, and facilitation of iterative development at the lab and the station and on the coastal ocean scale. MOSSCO is rich in metadata and its concepts are also applicable outside the coastal domain. For coastal modelling, it contains dozens of example coupling configurations and tested set-ups for coupled applications. Thus, MOSSCO addresses the technology needs of a growing marine coastal Earth system community that encompasses very different disciplines, numerical tools, and research questions.

DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

PubMed

Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

2009-08-07

DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

Toward a Model-Based Approach for Flight System Fault Protection

NASA Technical Reports Server (NTRS)

Day, John; Meakin, Peter; Murray, Alex

2012-01-01

Use SysML/UML to describe the physical structure of the system This part of the model would be shared with other teams - FS Systems Engineering, Planning & Execution, V&V, Operations, etc., in an integrated model-based engineering environment Use the UML Profile mechanism, defining Stereotypes to precisely express the concepts of the FP domain This extends the UML/SysML languages to contain our FP concepts Use UML/SysML, along with our profile, to capture FP concepts and relationships in the model Generate typical FP engineering products (the FMECA, Fault Tree, MRD, V&V Matrices)

Impulse response of a two-dimensional rough surface overlying an inhomogeneous, nondispersive medium: A hybrid model

NASA Astrophysics Data System (ADS)

Keiffer, Richard; Novarini, Jorge; Norton, Guy

2002-11-01

A numerical model to calculate the impulse response of a two-dimensional, impenetrable, rough surface directly in the time domain has been recently introduced [R. S. Keiffer and J. C. Novarini, J. Acoust. Soc. Am. 107, 27-39 (2000)]. This model is based on wedge diffraction theory and assumes the half-space containing the source and receiver is homogeneous. In this work, the model is extended to handle media where the index of refraction varies with depth by merging the scattering model with a ray-based propagation model. The resulting hybrid model is tested against a finite-difference time-domain (FDTD) method for backscattering from a corrugated surface in the presence of a refractive layer. This new model can be applied, for example, to calculate acoustic reverberation from the sea surface in cases where the water mass is inhomogeneous and dispersion is negligible. [Work supported by ONR/NRL (PE 61153N-32) and by grants of computer time DoD HPC Shared Resource Center at Stennis Space Center, MS.

Enhancing CIDOC-CRM and compatible models with the concept of multiple interpretation

NASA Astrophysics Data System (ADS)

Van Ruymbeke, M.; Hallot, P.; Billen, R.

2017-08-01

Modelling cultural heritage and archaeological objects is used as much for management as for research purposes. To ensure the sustainable benefit of digital data, models benefit from taking the data specificities of historical and archaeological domains into account. Starting from a conceptual model tailored to storing these specificities, we present, in this paper, an extended mapping to CIDOC-CRM and its compatible models. Offering an ideal framework to structure and highlight the best modelling practices, these ontologies are essentially dedicated to storing semantic data which provides information about cultural heritage objects. Based on this standard, our proposal focuses on multiple interpretation and sequential reality.

A hybrid hydrostatic and non-hydrostatic numerical model for shallow flow simulations

NASA Astrophysics Data System (ADS)

Zhang, Jingxin; Liang, Dongfang; Liu, Hua

2018-05-01

Hydrodynamics of geophysical flows in oceanic shelves, estuaries, and rivers, are often studied by solving shallow water model equations. Although hydrostatic models are accurate and cost efficient for many natural flows, there are situations where the hydrostatic assumption is invalid, whereby a fully hydrodynamic model is necessary to increase simulation accuracy. There is a growing concern about the decrease of the computational cost of non-hydrostatic pressure models to improve the range of their applications in large-scale flows with complex geometries. This study describes a hybrid hydrostatic and non-hydrostatic model to increase the efficiency of simulating shallow water flows. The basic numerical model is a three-dimensional hydrostatic model solved by the finite volume method (FVM) applied to unstructured grids. Herein, a second-order total variation diminishing (TVD) scheme is adopted. Using a predictor-corrector method to calculate the non-hydrostatic pressure, we extended the hydrostatic model to a fully hydrodynamic model. By localising the computational domain in the corrector step for non-hydrostatic pressure calculations, a hybrid model was developed. There was no prior special treatment on mode switching, and the developed numerical codes were highly efficient and robust. The hybrid model is applicable to the simulation of shallow flows when non-hydrostatic pressure is predominant only in the local domain. Beyond the non-hydrostatic domain, the hydrostatic model is still accurate. The applicability of the hybrid method was validated using several study cases.

Changes in children's self-competence and values: gender and domain differences across grades one through twelve.

PubMed

Jacobs, Janis E; Lanza, Stephanie; Osgood, D Wayne; Eccles, Jacquelynne S; Wigfield, Allan

2002-01-01

This study extended previous research on changes in children's self-beliefs by documenting domain-specific growth trajectories for 761 children across grades 1 through 12 in a longitudinal study of perceptions of self-competence and task values. Hierarchical Linear Modeling was used to (1) describe changes in beliefs across childhood and adolescence within the domains of mathematics, language arts, and sports; (2) examine the impact of changes in competence beliefs on changes in values over time in the same domains; and (3) describe gender differences in mean levels and trajectories of change in competence beliefs and values. The most striking finding across all domains was that self-perceptions of competence and subjective task values declined as children got older, although the extent and rate of decline varied across domains. For example, in language arts, competence beliefs declined rapidly during the elementary school years, but then leveled off or increased to some extent; whereas the decline in self-competence beliefs in sports accelerated during the high school years. Significant gender differences in beliefs were found in most domains; however, the gender differences in developmental trajectories appeared to be domain specific rather than global. Importantly, the gender differences between boys and girls did not systematically increase with age, as predicted by some socialization perspectives. Adding competence beliefs as an explanatory variable to the model for task values revealed that changes in competence beliefs accounted for much of the age-related decline in task values. In addition, competence beliefs accounted for most of the gender differences in task values for language arts and sports.

Personality Facets and All-Cause Mortality Among Medicare Patients Aged 66 to 102: A Follow-on Study of Weiss and Costa (2005)

PubMed Central

Costa, Paul T.; Weiss, Alexander; Duberstein, Paul R.; Friedman, Bruce; Siegler, Ilene C.

2014-01-01

Objectives To investigate associations between the personality factors and survival during 8 years follow-up. Methods Domains of personality and selected facet scores were assessed in 597 Medicare recipients (aged 66 to 102 years) who were followed up for approximately 8 years. Personality domains and factors were assessed using the Revised NEO Personality Inventory (NEO-PI-R). Using proportional hazards regression, the present study builds on a previous analysis of the NEO-PI-R domains and selected facet scores, which revealed that the Neuroticism facet Impulsiveness, Agreeableness facet Straightforwardness, and Conscientiousness facet Self-Discipline were related to longer life during 4 years of follow-up. In the present study, we extended the follow-up period by an additional 4 years, examining all 30 facets, and using accelerated failure time (AFT) modeling as an additional analytic approach. Unlike proportional hazards regression, AFT permits inferences about the median survival length conferred by predictors. Each facet was tested in a model that included health-related covariates and NEO-PI-R factor scores for dimensions that did not include that facet. Results Over the 8-year mortality surveillance period, Impulsiveness was not significant, but Straightforwardness and Self-Discipline remained significant predictors of longevity. When dichotomized, being high versus average or low on Self-Discipline was associated with an approximately 34% increase in median lifespan. Longer mortality surveillance also revealed that each standard deviation of Altruism, Compliance, Tender-Mindedness, and Openness to Fantasy was associated with an estimated 9–11% increase in median survival time. Conclusions After extending the follow-up period from 4 to 8 years, Self-Discipline remained a powerful predictor of survival. Facets associated with imagination, generosity, and higher quality interpersonal interactions become increasingly important when the follow-up period was extended to 8 years. PMID:24933014

Structure of the kinase domain of Gilgamesh from Drosophila melanogaster

PubMed Central

Han, Ni; Chen, CuiCui; Shi, Zhubing; Cheng, Dianlin

2014-01-01

The CK1 family kinases regulate multiple cellular aspects and play important roles in Wnt/Wingless and Hedgehog signalling. The kinase domain of Drosophila Gilgamesh isoform I (Gilgamesh-I), a homologue of human CK1-γ, was purified and crystallized. Crystals of methylated Gilgamesh-I kinase domain with a D210A mutation diffracted to 2.85 Å resolution and belonged to space group P43212, with unit-cell parameters a = b = 52.025, c = 291.727 Å. The structure of Gilgamesh-I kinase domain, which was determined by molecular replacement, has conserved catalytic elements and an active conformation. Structural comparison indicates that an extended loop between the α1 helix and the β4 strand exists in the Gilgamesh-I kinase domain. This extended loop may regulate the activity and function of Gilgamesh-I. PMID:24699734

An extended model based on the modified Nernst-Planck equation for describing transdermal iontophoresis of weak electrolytes.

PubMed

Imanidis, Georgios; Luetolf, Peter

2006-07-01

An extended model for iontophoretic enhancement of transdermal drug permeation under constant voltage is described based on the previously modified Nernst-Planck equation, which included the effect of convective solvent flow. This model resulted in an analytical expression for the enhancement factor as a function of applied voltage, convective flow velocity due to electroosmosis, ratio of lipid to aqueous pathway passive permeability, and weighted average net ionic valence of the permeant in the aqueous epidermis domain. The shift of pH in the epidermis compared to bulk caused by the electrical double layer at the lipid-aqueous domain interface was evaluated using the Poisson-Boltzmann equation. This was solved numerically for representative surface charge densities and yielded pH differences between bulk and epidermal aqueous domain between 0.05 and 0.4 pH units. The developed model was used to analyze the experimental enhancement of an amphoteric weak electrolyte measured in vitro using human cadaver epidermis and a voltage of 250 mV at different pH values. Parameter values characterizing the involved factors were determined that yielded the experimental enhancement factors and passive permeability coefficients at all pH values. The model provided a very good agreement between experimental and calculated enhancement and passive permeability. The deduced parameters showed (i) that the pH shift in the aqueous permeation pathway had a notable effect on the ionic valence and the partitioning of the drug in this domain for a high surface charge density and depending on the pK(a) and pI of the drug in relation to the bulk pH; (ii) the magnitude and the direction of convective transport due to electroosmosis typically reflected the density and sign, respectively, of surface charge of the tissue and its effect on enhancement was substantial for bulk pH values differing from the pI of epidermal tissue; (iii) the aqueous pathway predominantly determined passive permeability of the studied compound despite its measurable lipophilicity and therefore the lipid pathway did not notably affect enhancement. Hence, the proposed model can provide a good quantitative insight into the interplay between different phenomena and permeant properties influencing iontophoresis and can potentially be used as a predictive tool of the process.

Time-domain simulation of flute-like instruments: comparison of jet-drive and discrete-vortex models.

PubMed

Auvray, Roman; Ernoult, Augustin; Fabre, Benoît; Lagrée, Pierre-Yves

2014-07-01

This paper presents two models of sound production in flute-like instruments that allow time-domain simulations. The models are based on different descriptions of the jet flow within the window of the instrument. The jet-drive model depicts the jet by its transverse perturbation that interacts with the labium to produce sound. The discrete-vortex model depicts the jet as two independent shear layers along which vortices are convected and interact with the acoustic field within the window. The limit of validity between both models is usually discussed according to the aspect ratio of the jet W/h, with W the window length and h the flue channel height. The present simulations, compared with experimental data gathered on a recorder, allow to extend the aspect ratio criterion to the notion of dynamic aspect ratio defined as λ/h where λ is the hydrodynamic wavelength that now accounts for geometrical properties, such as W/h, as well as for dynamic properties, such as the Strouhal number. The two models are found to be applicable over neighboring values of geometry and blowing pressure.

A fictitious domain approach for the Stokes problem based on the extended finite element method

NASA Astrophysics Data System (ADS)

Court, Sébastien; Fournié, Michel; Lozinski, Alexei

2014-01-01

In the present work, we propose to extend to the Stokes problem a fictitious domain approach inspired by eXtended Finite Element Method and studied for Poisson problem in [Renard]. The method allows computations in domains whose boundaries do not match. A mixed finite element method is used for fluid flow. The interface between the fluid and the structure is localized by a level-set function. Dirichlet boundary conditions are taken into account using Lagrange multiplier. A stabilization term is introduced to improve the approximation of the normal trace of the Cauchy stress tensor at the interface and avoid the inf-sup condition between the spaces for velocity and the Lagrange multiplier. Convergence analysis is given and several numerical tests are performed to illustrate the capabilities of the method.

GAMBIT: A Parameterless Model-Based Evolutionary Algorithm for Mixed-Integer Problems.

PubMed

Sadowski, Krzysztof L; Thierens, Dirk; Bosman, Peter A N

2018-01-01

Learning and exploiting problem structure is one of the key challenges in optimization. This is especially important for black-box optimization (BBO) where prior structural knowledge of a problem is not available. Existing model-based Evolutionary Algorithms (EAs) are very efficient at learning structure in both the discrete, and in the continuous domain. In this article, discrete and continuous model-building mechanisms are integrated for the Mixed-Integer (MI) domain, comprising discrete and continuous variables. We revisit a recently introduced model-based evolutionary algorithm for the MI domain, the Genetic Algorithm for Model-Based mixed-Integer opTimization (GAMBIT). We extend GAMBIT with a parameterless scheme that allows for practical use of the algorithm without the need to explicitly specify any parameters. We furthermore contrast GAMBIT with other model-based alternatives. The ultimate goal of processing mixed dependences explicitly in GAMBIT is also addressed by introducing a new mechanism for the explicit exploitation of mixed dependences. We find that processing mixed dependences with this novel mechanism allows for more efficient optimization. We further contrast the parameterless GAMBIT with Mixed-Integer Evolution Strategies (MIES) and other state-of-the-art MI optimization algorithms from the General Algebraic Modeling System (GAMS) commercial algorithm suite on problems with and without constraints, and show that GAMBIT is capable of solving problems where variable dependences prevent many algorithms from successfully optimizing them.

Global Federation of Data Services in Seismology: Extending the Concept to Interdisciplinary Science

NASA Astrophysics Data System (ADS)

Ahern, T. K.; Trabant, C. M.; Stults, M.; Van Fossen, M.

2015-12-01

The International Federation of Digital Seismograph Networks (FDSN) sets international standards, formats, and access protocols for global seismology. Recently the availability of an FDSN standard for web services has enabled the development of a federated model of data access. With a growing number of internationally distributed data centers supporting identical web services the task of federation is now fully realizable. This presentation will highlight the advances the seismological community has made in the past year towards federated access to seismological data including waveforms, earthquake event catalogs, and metadata describing seismic stations. As part of the NSF EarthCube project, IRIS and its partners have been extending the concept of standard web services to other domains. Our primary partners include Lamont Doherty Earth Observatory (marine geophysics), Caltech (tectonic plate reconstructions), SDSC (hydrology), UNAVCO (geodesy), and Unidata (atmospheric sciences). Additionally IRIS is working with partners at NOAA's NGDC, NEON, UTEP, WOVODAT, Intermagnet, Global Geodynamics Program, and the Ocean Observatory Initiative (OOI) to develop web services for those domains. The ultimate goal is to allow discovery, access, and utilization of cross-domain data sources. IRIS and a variety of US and European partners have been involved in the Cooperation between Europe and the US (CoopEUS) project where interdisciplinary data integration is a key topic.

Domain adaptation via transfer component analysis.

PubMed

Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

2011-02-01

Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

PyMT: A Python package for model-coupling in the Earth sciences

NASA Astrophysics Data System (ADS)

Hutton, E.

2016-12-01

The current landscape of Earth-system models is not only broad in scientific scope, but also broad in type. On the one hand, the large variety of models is exciting, as it provides fertile ground for extending or linking models together in novel ways to answer new scientific questions. However, the heterogeneity in model type acts to inhibit model coupling, model development, or even model use. Existing models are written in a variety of programming languages, operate on different grids, use their own file formats (both for input and output), have different user interfaces, have their own time steps, etc. Each of these factors become obstructions to scientists wanting to couple, extend - or simply run - existing models. For scientists whose main focus may not be computer science these barriers become even larger and become significant logistical hurdles. And this is all before the scientific difficulties of coupling or running models are addressed. The CSDMS Python Modeling Toolkit (PyMT) was developed to help non-computer scientists deal with these sorts of modeling logistics. PyMT is the fundamental package the Community Surface Dynamics Modeling System uses for the coupling of models that expose the Basic Modeling Interface (BMI). It contains: Tools necessary for coupling models of disparate time and space scales (including grid mappers) Time-steppers that coordinate the sequencing of coupled models Exchange of data between BMI-enabled models Wrappers that automatically load BMI-enabled models into the PyMT framework Utilities that support open-source interfaces (UGRID, SGRID,CSDMS Standard Names, etc.) A collection of community-submitted models, written in a variety of programminglanguages, from a variety of process domains - but all usable from within the Python programming language A plug-in framework for adding additional BMI-enabled models to the framework In this presentation we intoduce the basics of the PyMT as well as provide an example of coupling models of different domains and grid types.

Achieving interoperability for metadata registries using comparative object modeling.

PubMed

Park, Yu Rang; Kim, Ju Han

2010-01-01

Achieving data interoperability between organizations relies upon agreed meaning and representation (metadata) of data. For managing and registering metadata, many organizations have built metadata registries (MDRs) in various domains based on international standard for MDR framework, ISO/IEC 11179. Following this trend, two pubic MDRs in biomedical domain have been created, United States Health Information Knowledgebase (USHIK) and cancer Data Standards Registry and Repository (caDSR), from U.S. Department of Health & Human Services and National Cancer Institute (NCI), respectively. Most MDRs are implemented with indiscriminate extending for satisfying organization-specific needs and solving semantic and structural limitation of ISO/IEC 11179. As a result it is difficult to address interoperability among multiple MDRs. In this paper, we propose an integrated metadata object model for achieving interoperability among multiple MDRs. To evaluate this model, we developed an XML Schema Definition (XSD)-based metadata exchange format. We created an XSD-based metadata exporter, supporting both the integrated metadata object model and organization-specific MDR formats.

Extension of continental lithosphere - A model for two scales of basin and range deformation

NASA Technical Reports Server (NTRS)

Zuber, M. T.; Parmentier, E. M.; Fletcher, R. C.

1986-01-01

The development of a model for deformation in an extending continental lithosphere that is stratified in density and strength is described. The lithosphere model demonstrates that the necking instabilities at two wavelengths originate due to a strong upper crust, a mantle layer, and a weak lower crust. It is observed that the dominant wavelengths of necking are controlled by layer thickness and the strength of the layers control the amplitude of the instabilities. The model is applied to the Basin and Range Province of the western U.S. where deformations in ranges and tile domains are detected. The relation between the Bouguer gravity anomaly and the deformations is studied. The data reveal that the horizontal scale of short wavelength necking correlates with the spacings of individual basins and ranges, and the longer wavelength corresponds to the width of tilt domains. The control of the Basin and Range deformation by two scales of extensional instability is proposed.

Including Magnetostriction in Micromagnetic Models

NASA Astrophysics Data System (ADS)

Conbhuí, Pádraig Ó.; Williams, Wyn; Fabian, Karl; Nagy, Lesleis

2016-04-01

The magnetic anomalies that identify crustal spreading are predominantly recorded by basalts formed at the mid-ocean ridges, whose magnetic signals are dominated by iron-titanium-oxides (Fe3-xTixO4), so called "titanomagnetites", of which the Fe2.4Ti0.6O4 (TM60) phase is the most common. With sufficient quantities of titanium present, these minerals exhibit strong magnetostriction. To date, models of these grains in the pseudo-single domain (PSD) range have failed to accurately account for this effect. In particular, a popular analytic treatment provided by Kittel (1949) for describing the magnetostrictive energy as an effective increase of the anisotropy constant can produce unphysical strains for non-uniform magnetizations. I will present a rigorous approach based on work by Brown (1966) and by Kroner (1958) for including magnetostriction in micromagnetic codes which is suitable for modelling hysteresis loops and finding remanent states in the PSD regime. Preliminary results suggest the more rigorously defined micromagnetic models exhibit higher coercivities and extended single domain ranges when compared to more simplistic approaches.

CRYSTAL-FACE Analysis and Simulations of the July 23rd Extended Anvil Case

NASA Technical Reports Server (NTRS)

Starr, David

2003-01-01

A key focus of CRYSTAL-FACE (Cirrus Regional Study of Tropical Anvils and cirrus Layers - Florida Area Cirrus Experiment) was the generation and subsequent evolution of cirrus outflow from deep convective cloud systems. Present theoretical background and motivations will be discussed. An integrated look at the observations of an extended cirrus anvil cloud system observed on 23 July 2002 will be presented, including lidar and millimeter radar observation; from NASA s ER-2 and in-situ observations from NASA s WB-57 and University of North Dakota Citation. The observations will be compared to results of simulations using 1-D and 2-D high-resolution (100 meter) cloud resolving models. The CRMs explicitly account for cirrus microphysical development by resolving the evolving ice crystal size distribution (bin model) in time and space. Both homogeneous and heterogeneous nucleation are allowed in the model. The CRM simulations are driven using the output of regional simulations using MM5 that produces deep convection similar to what was observed. The MM5 model employs a 2 km inner grid (32 layers) over a 360 km domain, nested within a 6-km grid over a 600-km domain. Initial and boundary conditions for the 36-hour MM5 simulation are taken from NCEP Eta model analysis at 32 km resolution. Key issues to be explored are the settling of the observed anvil versus the model simulations, and comparisons of dynamical properties, such as vertical motions, occurring in the observations and models. The former provides an integrated measure of the validity of the model microphysics (fallspeed) while the latter is the key factor in forcing continued ice generation.

Noise Radiation From a Leading-Edge Slat

NASA Technical Reports Server (NTRS)

Lockard, David P.; Choudhari, Meelan M.

2009-01-01

This paper extends our previous computations of unsteady flow within the slat cove region of a multi-element high-lift airfoil configuration, which showed that both statistical and structural aspects of the experimentally observed unsteady flow behavior can be captured via 3D simulations over a computational domain of narrow spanwise extent. Although such narrow domain simulation can account for the spanwise decorrelation of the slat cove fluctuations, the resulting database cannot be applied towards acoustic predictions of the slat without invoking additional approximations to synthesize the fluctuation field over the rest of the span. This deficiency is partially alleviated in the present work by increasing the spanwise extent of the computational domain from 37.3% of the slat chord to nearly 226% (i.e., 15% of the model span). The simulation database is used to verify consistency with previous computational results and, then, to develop predictions of the far-field noise radiation in conjunction with a frequency-domain Ffowcs-Williams Hawkings solver.

A new kinematic model for the Mesozoic evolution of the Iberia plate

NASA Astrophysics Data System (ADS)

Nirrengarten, Michael; Manatschal, Gianreto; Tugend, Julie; Kusznir, Nick; Sauter, Daniel

2017-04-01

During the Mesozoic Iberia was progressively surrounded by rift systems leading to its transient individualization as a tectonic plate. The kinematic evolution of Iberia prior to oceanic magnetic anomaly C34 ( 83 Ma) is controversial. To date, no kinematic models accounts for the Late Aptian to Albian hyper-extended rift phase observed in the Pyrenees. Consistent isochronal features, such as oceanic magnetic anomalies, representing the backbones of oceanic plate reconstructions are lacking. The only potential candidate, the J-anomaly, located offshore Iberia and Newfoundland has recently been re-interpreted as resulting from polyphased and polygenic magmatic events and does not provide a useful constraint. We use a new reconstruction approach that integrates the spatio-temporal evolution of adjacent hyper-extended rift domains systems to investigate Iberia plate motion during the separation of the super-continent Pangea. The plate modeling is based on careful mapping and restoration of the rift domains with key rift events dated within the study area. The main outcomes of this new model are as follows: 1) A full-fit of the southern North Atlantic 2) Extension on the southern and eastern boundary of Iberia related to the opening of the Central Atlantic 3) Segmentation of the Iberia-Newfoundland rift system by fracture zones prior to a V-shape propagation of mantle exhumation and seafloor spreading 4) No Aptian subduction in the Pyrenean domain and a limited rotation of the Iberia plate 5) The partitioning of deformation between different micro-blocks along the Iberian-Eurasian boundary enabling Late Aptian to Albian extension in the Pyrenees The resulting plate kinematic model for Iberia differs from previous ones on three main points: it does not make use of the J magnetic anomaly because the J anomlay is neither an isochron or a COB marker; the deformation along the Iberian-Eurasian boundary is partitioned between distinct rift systems; and it incorporates extension in the Pyrenees consistent with published geological studies. Nonetheless this model is non-unique and additional observations are needed to further constrain the plate modeling notably by adding new constraints on the rift evolution of the southern and eastern margin of the Iberia plate during the Jurassic.

Acoustic Treatment Design Scaling Methods. Phase 2

NASA Technical Reports Server (NTRS)

Clark, L. (Technical Monitor); Parrott, T. (Technical Monitor); Jones, M. (Technical Monitor); Kraft, R. E.; Yu, J.; Kwan, H. W.; Beer, B.; Seybert, A. F.; Tathavadekar, P.

2003-01-01

The ability to design, build and test miniaturized acoustic treatment panels on scale model fan rigs representative of full scale engines provides not only cost-savings, but also an opportunity to optimize the treatment by allowing multiple tests. To use scale model treatment as a design tool, the impedance of the sub-scale liner must be known with confidence. This study was aimed at developing impedance measurement methods for high frequencies. A normal incidence impedance tube method that extends the upper frequency range to 25,000 Hz. without grazing flow effects was evaluated. The free field method was investigated as a potential high frequency technique. The potential of the two-microphone in-situ impedance measurement method was evaluated in the presence of grazing flow. Difficulties in achieving the high frequency goals were encountered in all methods. Results of developing a time-domain finite difference resonator impedance model indicated that a re-interpretation of the empirical fluid mechanical models used in the frequency domain model for nonlinear resistance and mass reactance may be required. A scale model treatment design that could be tested on the Universal Propulsion Simulator vehicle was proposed.

Meta-analysis of diagnostic test data: a bivariate Bayesian modeling approach.

PubMed

Verde, Pablo E

2010-12-30

In the last decades, the amount of published results on clinical diagnostic tests has expanded very rapidly. The counterpart to this development has been the formal evaluation and synthesis of diagnostic results. However, published results present substantial heterogeneity and they can be regarded as so far removed from the classical domain of meta-analysis, that they can provide a rather severe test of classical statistical methods. Recently, bivariate random effects meta-analytic methods, which model the pairs of sensitivities and specificities, have been presented from the classical point of view. In this work a bivariate Bayesian modeling approach is presented. This approach substantially extends the scope of classical bivariate methods by allowing the structural distribution of the random effects to depend on multiple sources of variability. Meta-analysis is summarized by the predictive posterior distributions for sensitivity and specificity. This new approach allows, also, to perform substantial model checking, model diagnostic and model selection. Statistical computations are implemented in the public domain statistical software (WinBUGS and R) and illustrated with real data examples. Copyright © 2010 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less

Protein–Protein Interactions Modulate the Docking-Dependent E3-Ubiquitin Ligase Activity of Carboxy-Terminus of Hsc70-Interacting Protein (CHIP)*

PubMed Central

Narayan, Vikram; Landré, Vivien; Ning, Jia; Hernychova, Lenka; Muller, Petr; Verma, Chandra; Walkinshaw, Malcolm D.; Blackburn, Elizabeth A.; Ball, Kathryn L.

2015-01-01

CHIP is a tetratricopeptide repeat (TPR) domain protein that functions as an E3-ubiquitin ligase. As well as linking the molecular chaperones to the ubiquitin proteasome system, CHIP also has a docking-dependent mode where it ubiquitinates native substrates, thereby regulating their steady state levels and/or function. Here we explore the effect of Hsp70 on the docking-dependent E3-ligase activity of CHIP. The TPR-domain is revealed as a binding site for allosteric modulators involved in determining CHIP's dynamic conformation and activity. Biochemical, biophysical and modeling evidence demonstrate that Hsp70-binding to the TPR, or Hsp70-mimetic mutations, regulate CHIP-mediated ubiquitination of p53 and IRF-1 through effects on U-box activity and substrate binding. HDX-MS was used to establish that conformational-inhibition-signals extended from the TPR-domain to the U-box. This underscores inter-domain allosteric regulation of CHIP by the core molecular chaperones. Defining the chaperone-associated TPR-domain of CHIP as a manager of inter-domain communication highlights the potential for scaffolding modules to regulate, as well as assemble, complexes that are fundamental to protein homeostatic control. PMID:26330542

PSPs and ERPs: applying the dynamics of post-synaptic potentials to individual units in simulation of temporally extended Event-Related Potential reading data.

PubMed

Laszlo, Sarah; Armstrong, Blair C

2014-05-01

The Parallel Distributed Processing (PDP) framework is built on neural-style computation, and is thus well-suited for simulating the neural implementation of cognition. However, relatively little cognitive modeling work has concerned neural measures, instead focusing on behavior. Here, we extend a PDP model of reading-related components in the Event-Related Potential (ERP) to simulation of the N400 repetition effect. We accomplish this by incorporating the dynamics of cortical post-synaptic potentials--the source of the ERP signal--into the model. Simulations demonstrate that application of these dynamics is critical for model elicitation of repetition effects in the time and frequency domains. We conclude that by advancing a neurocomputational understanding of repetition effects, we are able to posit an interpretation of their source that is both explicitly specified and mechanistically different from the well-accepted cognitive one. Copyright © 2014 Elsevier Inc. All rights reserved.

Fluid-structure interaction with the entropic lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Dorschner, B.; Chikatamarla, S. S.; Karlin, I. V.

2018-02-01

We propose a fluid-structure interaction (FSI) scheme using the entropic multi-relaxation time lattice Boltzmann (KBC) model for the fluid domain in combination with a nonlinear finite element solver for the structural part. We show the validity of the proposed scheme for various challenging setups by comparison to literature data. Beyond validation, we extend the KBC model to multiphase flows and couple it with a finite element method (FEM) solver. Robustness and viability of the entropic multi-relaxation time model for complex FSI applications is shown by simulations of droplet impact on elastic superhydrophobic surfaces.

Transactional relationships among cognitive vulnerabilities, stressors, and depressive symptoms in adolescence.

PubMed

Calvete, Esther; Orue, Izaskun; Hankin, Benjamin L

2013-04-01

The transactional cognitive vulnerability to stress model Hankin & Abramson (Psychological Bulletin, 127:773-796, 2001) extends the traditional diathesis-stress model by proposing that the relationships among cognitions, depressive symptoms, and stressors are dynamic and bidirectional. In this study three different pathways among these variables were assessed simultaneously: (1) cognitive vulnerabilities and stressors as predictors of depressive symptoms (vulnerability model), (2) depressive symptoms and cognitive vulnerabilities as predictors of stressors (stress generation model), and (3) depressive symptoms and stressors as predictors of cognitive vulnerabilities (consequence model). A fully cross-lagged design panel was employed with 1,187 adolescents (545 girls and 642 boys, Mean Age = 13.42 years) who were assessed at two time points separated by 6 months. They completed measures of cognitive vulnerabilities (maladaptive schema domains and negative inferential style), stressors, and depressive symptoms. Inferential style and schemas of the disconnection and rejection domain predicted prospective increases in depressive symptoms. Initial levels of depressive symptoms and most cognitive vulnerabilities predicted greater stress generation. Initial levels of stressors and depressive symptoms predicted an increase in negative inferential style and maladaptive schema domains over time. These bidirectional relationships were mostly similar for boys and girls, although there were a few gender differences. The findings support a transactional model with reciprocal relationships among stress, depressive symptoms, and cognitive vulnerabilities. Transactional implications for depression interventions among adolescents are discussed.

Global Federation of Data Services in Seismology: Extending the Concept to Interdisciplinary Science

NASA Astrophysics Data System (ADS)

Ahern, Tim; Trabant, Chad; Stults, Mike; VanFossen, Mick

2016-04-01

The International Federation of Digital Seismograph Networks (FDSN) sets international standards, formats, and access protocols for global seismology. Recently the availability of an FDSN standard for web services has enabled the development of a federated model of data access. With a growing number of internationally distributed data centers supporting compatible web services the task of federation is now fully realizable. The utility of this approach is already starting to bear fruit in seismology. This presentation will highlight the advances the seismological community has made in the past year towards federated access to seismological data including waveforms, earthquake event catalogs, and metadata describing seismic stations. It will include a discussion of an IRIS Federator as well as an emerging effort to develop an FDSN Federator that will allow seamless access to seismological information across multiple FDSN data centers. As part of the NSF EarthCube initiative as well as the US-European data coordination project (COOPEUS), IRIS and several partners, collectively called GeoWS, have been extending the concept of standard web services to other domains. Our primary partners include Lamont Doherty Earth Observatory (marine geophysics), Caltech (tectonic plate reconstructions), SDSC (hydrology), UNAVCO (geodesy), and Unidata (atmospheric sciences). Additionally, IRIS is working with partners at NOAA's National Centers for Environmental Information (NCEI) , NEON, UTEP, WOVOdat, INTERMAGNET, Global Geodynamics Program, and the Ocean Observatory Initiative (OOI) to develop web services for those domains. The ultimate goal is to allow discovery, access, and utilization of cross-domain data sources. One of the significant outcomes of this effort is the development of a simple text and metadata representation for tabular data called GeoCSV, that allows straightforward interpretation of information from multiple domains by non-domain experts.

Reconstruction of transient vibration and sound radiation of an impacted plate using time domain plane wave superposition method

NASA Astrophysics Data System (ADS)

Geng, Lin; Zhang, Xiao-Zheng; Bi, Chuan-Xing

2015-05-01

Time domain plane wave superposition method is extended to reconstruct the transient pressure field radiated by an impacted plate and the normal acceleration of the plate. In the extended method, the pressure measured on the hologram plane is expressed as a superposition of time convolutions between the time-wavenumber normal acceleration spectrum on a virtual source plane and the time domain propagation kernel relating the pressure on the hologram plane to the normal acceleration spectrum on the virtual source plane. By performing an inverse operation, the normal acceleration spectrum on the virtual source plane can be obtained by an iterative solving process, and then taken as the input to reconstruct the whole pressure field and the normal acceleration of the plate. An experiment of a clamped rectangular steel plate impacted by a steel ball is presented. The experimental results demonstrate that the extended method is effective in visualizing the transient vibration and sound radiation of an impacted plate in both time and space domains, thus providing the important information for overall understanding the vibration and sound radiation of the plate.

Future Research Directions in the Positive Valence Systems: Measurement, Development, and Implications for Youth Unipolar Depression.

PubMed

Olino, Thomas M

2016-01-01

The Positive Valence Systems (PVS) have been introduced by the National Institute of Mental Health as a domain to help organize multiple constructs focusing on reward-seeking behaviors. However, the initial working model for this domain is strongly influenced by adult constructs and measures. Thus, the present review focuses on extending the PVS into a developmental context. Specifically, the review provides some hypotheses about the structure of the PVS, how PVS components may change throughout development, how family history of depression may influence PVS development, and potential means of intervening on PVS function to reduce onsets of depression. Future research needs in each of these areas are highlighted.

A model for occupational safety and health intervention diffusion to small businesses.

PubMed

Sinclair, Raymond C; Cunningham, Thomas R; Schulte, Paul A

2013-12-01

Smaller businesses differ from their larger counterparts in having higher rates of occupational injuries and illnesses and fewer resources for preventing those losses. Intervention models developed outside the United States have addressed the resource deficiency issue by incorporating intermediary organizations such as trade associations. This paper extends previous models by using exchange theory and by borrowing from the diffusion of innovations model. It emphasizes that occupational safety and health (OSH) organizations must understand as much about intermediary organizations as they do about small businesses. OSH organizations ("initiators") must understand how to position interventions and information to intermediaries as added value to their relationships with small businesses. Examples from experiences in two midwestern states are used to illustrate relationships and types of analyses implied by the extended model. The study found that intermediary organizations were highly attuned to providing smaller businesses with what they want, including OSH services. The study also found that there are opinion leader organizations and individual champions within intermediaries who are key to decisions and actions about OSH programming. The model places more responsibility on both initiators and intermediaries to develop and market interventions that will be valued in the competitive small business environment where the resources required to adopt each new business activity could always be used in other ways. The model is a candidate for empirical validation, and it offers some encouragement that the issue of sustainable OSH assistance to small businesses might be addressed. Am. J. Ind. Med. 56:1442-1451, 2013. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

The Utility of the Extended Images in Ambient Seismic Wavefield Migration

NASA Astrophysics Data System (ADS)

Girard, A. J.; Shragge, J. C.

2015-12-01

Active-source 3D seismic migration and migration velocity analysis (MVA) are robust and highly used methods for imaging Earth structure. One class of migration methods uses extended images constructed by incorporating spatial and/or temporal wavefield correlation lags to the imaging conditions. These extended images allow users to directly assess whether images focus better with different parameters, which leads to MVA techniques that are based on the tenets of adjoint-state theory. Under certain conditions (e.g., geographical, cultural or financial), however, active-source methods can prove impractical. Utilizing ambient seismic energy that naturally propagates through the Earth is an alternate method currently used in the scientific community. Thus, an open question is whether extended images are similarly useful for ambient seismic migration processing and verifying subsurface velocity models, and whether one can similarly apply adjoint-state methods to perform ambient migration velocity analysis (AMVA). Herein, we conduct a number of numerical experiments that construct extended images from ambient seismic recordings. We demonstrate that, similar to active-source methods, there is a sensitivity to velocity in ambient seismic recordings in the migrated extended image domain. In synthetic ambient imaging tests with varying degrees of error introduced to the velocity model, the extended images are sensitive to velocity model errors. To determine the extent of this sensitivity, we utilize acoustic wave-equation propagation and cross-correlation-based migration methods to image weak body-wave signals present in the recordings. Importantly, we have also observed scenarios where non-zero correlation lags show signal while zero-lags show none. This may be a valuable missing piece for ambient migration techniques that have yielded largely inconclusive results, and might be an important piece of information for performing AMVA from ambient seismic recordings.

Domain learning naming game for color categorization.

PubMed

Li, Doujie; Fan, Zhongyan; Tang, Wallace K S

2017-01-01

Naming game simulates the evolution of vocabulary in a population of agents. Through pairwise interactions in the games, agents acquire a set of vocabulary in their memory for object naming. The existing model confines to a one-to-one mapping between a name and an object. Focus is usually put onto name consensus in the population rather than knowledge learning in agents, and hence simple learning model is usually adopted. However, the cognition system of human being is much more complex and knowledge is usually presented in a complicated form. Therefore, in this work, we extend the agent learning model and design a new game to incorporate domain learning, which is essential for more complicated form of knowledge. In particular, we demonstrate the evolution of color categorization and naming in a population of agents. We incorporate the human perceptive model into the agents and introduce two new concepts, namely subjective perception and subliminal stimulation, in domain learning. Simulation results show that, even without any supervision or pre-requisition, a consensus of a color naming system can be reached in a population solely via the interactions. Our work confirms the importance of society interactions in color categorization, which is a long debate topic in human cognition. Moreover, our work also demonstrates the possibility of cognitive system development in autonomous intelligent agents.

Domain learning naming game for color categorization

PubMed Central

2017-01-01

Naming game simulates the evolution of vocabulary in a population of agents. Through pairwise interactions in the games, agents acquire a set of vocabulary in their memory for object naming. The existing model confines to a one-to-one mapping between a name and an object. Focus is usually put onto name consensus in the population rather than knowledge learning in agents, and hence simple learning model is usually adopted. However, the cognition system of human being is much more complex and knowledge is usually presented in a complicated form. Therefore, in this work, we extend the agent learning model and design a new game to incorporate domain learning, which is essential for more complicated form of knowledge. In particular, we demonstrate the evolution of color categorization and naming in a population of agents. We incorporate the human perceptive model into the agents and introduce two new concepts, namely subjective perception and subliminal stimulation, in domain learning. Simulation results show that, even without any supervision or pre-requisition, a consensus of a color naming system can be reached in a population solely via the interactions. Our work confirms the importance of society interactions in color categorization, which is a long debate topic in human cognition. Moreover, our work also demonstrates the possibility of cognitive system development in autonomous intelligent agents. PMID:29136661

Advanced EMT and Phasor-Domain Hybrid Simulation with Simulation Mode Switching Capability for Transmission and Distribution Systems

DOE PAGES

Huang, Qiuhua; Vittal, Vijay

2018-05-09

Conventional electromagnetic transient (EMT) and phasor-domain hybrid simulation approaches presently exist for trans-mission system level studies. Their simulation efficiency is generally constrained by the EMT simulation. With an increasing number of distributed energy resources and non-conventional loads being installed in distribution systems, it is imperative to extend the hybrid simulation application to include distribution systems and integrated transmission and distribution systems. Meanwhile, it is equally important to improve the simulation efficiency as the modeling scope and complexity of the detailed system in the EMT simulation increases. To meet both requirements, this paper introduces an advanced EMT and phasor-domain hybrid simulationmore » approach. This approach has two main features: 1) a comprehensive phasor-domain modeling framework which supports positive-sequence, three-sequence, three-phase and mixed three-sequence/three-phase representations and 2) a robust and flexible simulation mode switching scheme. The developed scheme enables simulation switching from hybrid simulation mode back to pure phasor-domain dynamic simulation mode to achieve significantly improved simulation efficiency. The proposed method has been tested on integrated transmission and distribution systems. In conclusion, the results show that with the developed simulation switching feature, the total computational time is significantly reduced compared to running the hybrid simulation for the whole simulation period, while maintaining good simulation accuracy.« less

Advanced EMT and Phasor-Domain Hybrid Simulation with Simulation Mode Switching Capability for Transmission and Distribution Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Qiuhua; Vittal, Vijay

Conventional electromagnetic transient (EMT) and phasor-domain hybrid simulation approaches presently exist for trans-mission system level studies. Their simulation efficiency is generally constrained by the EMT simulation. With an increasing number of distributed energy resources and non-conventional loads being installed in distribution systems, it is imperative to extend the hybrid simulation application to include distribution systems and integrated transmission and distribution systems. Meanwhile, it is equally important to improve the simulation efficiency as the modeling scope and complexity of the detailed system in the EMT simulation increases. To meet both requirements, this paper introduces an advanced EMT and phasor-domain hybrid simulationmore » approach. This approach has two main features: 1) a comprehensive phasor-domain modeling framework which supports positive-sequence, three-sequence, three-phase and mixed three-sequence/three-phase representations and 2) a robust and flexible simulation mode switching scheme. The developed scheme enables simulation switching from hybrid simulation mode back to pure phasor-domain dynamic simulation mode to achieve significantly improved simulation efficiency. The proposed method has been tested on integrated transmission and distribution systems. In conclusion, the results show that with the developed simulation switching feature, the total computational time is significantly reduced compared to running the hybrid simulation for the whole simulation period, while maintaining good simulation accuracy.« less

Statistics of opinion domains of the majority-vote model on a square lattice

NASA Astrophysics Data System (ADS)

Peres, Lucas R.; Fontanari, José F.

2010-10-01

The existence of juxtaposed regions of distinct cultures in spite of the fact that people’s beliefs have a tendency to become more similar to each other’s as the individuals interact repeatedly is a puzzling phenomenon in the social sciences. Here we study an extreme version of the frequency-dependent bias model of social influence in which an individual adopts the opinion shared by the majority of the members of its extended neighborhood, which includes the individual itself. This is a variant of the majority-vote model in which the individual retains its opinion in case there is a tie among the neighbors’ opinions. We assume that the individuals are fixed in the sites of a square lattice of linear size L and that they interact with their nearest neighbors only. Within a mean-field framework, we derive the equations of motion for the density of individuals adopting a particular opinion in the single-site and pair approximations. Although the single-site approximation predicts a single opinion domain that takes over the entire lattice, the pair approximation yields a qualitatively correct picture with the coexistence of different opinion domains and a strong dependence on the initial conditions. Extensive Monte Carlo simulations indicate the existence of a rich distribution of opinion domains or clusters, the number of which grows with L2 whereas the size of the largest cluster grows with lnL2 . The analysis of the sizes of the opinion domains shows that they obey a power-law distribution for not too large sizes but that they are exponentially distributed in the limit of very large clusters. In addition, similarly to other well-known social influence model—Axelrod’s model—we found that these opinion domains are unstable to the effect of a thermal-like noise.

Dynamic train-turnout interaction in an extended frequency range using a detailed model of track dynamics

NASA Astrophysics Data System (ADS)

Kassa, Elias; Nielsen, Jens C. O.

2009-03-01

A time domain solution method for general three-dimensional dynamic interaction of train and turnout (switch and crossing) that accounts for excitation in an extended frequency range (up to several hundred Hz) is proposed. Based on a finite element (FE) model of a standard turnout design, a complex-valued modal superposition of track dynamics is applied using the first 500 eigenmodes of the turnout model. The three-dimensional model includes the distribution of structural flexibility along the turnout, such as bending and torsion of rails and sleepers, and the variations in rail cross-section and sleeper length. Convergence of simulation results is studied while using an increasing number of eigenmodes. It is shown that modes with eigenfrequencies up to at least 200 Hz have a significant influence on the magnitudes of the wheel-rail contact forces. Results from using a simplified track model with a commercial computer program for low-frequency vehicle dynamics are compared with the results from using the detailed FE model in conjunction with the proposed method.

Acoustic valley edge states in a graphene-like resonator system

NASA Astrophysics Data System (ADS)

Yang, Yahui; Yang, Zhaoju; Zhang, Baile

2018-03-01

The concept of valley physics, as inspired by the recent development in valleytronic materials, has been extended to acoustic crystals for manipulation of air-borne sound. Many valleytronic materials follow the model of a gapped graphene. Yet the previously demonstrated valley acoustic crystal adopted a mirror-symmetry-breaking mechanism, lacking a direct counterpart in condensed matter systems. In this paper, we investigate a two-dimensional (2D) periodic acoustic resonator system with inversion symmetry breaking, as an analogue of a gapped graphene monolayer. It demonstrates the quantum valley Hall topological phase for sound waves. Similar to a gapped graphene, gapless topological valley edge states can be found at a zigzag domain wall separating different domains with opposite valley Chern numbers, while an armchair domain wall hosts no gapless edge states. Our study offers a route to simulate novel valley phenomena predicted in gapped graphene and other 2D materials with classical acoustic waves.

Proving refinement transformations using extended denotational semantics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winter, V.L.; Boyle, J.M.

1996-04-01

TAMPR is a fully automatic transformation system based on syntactic rewrites. Our approach in a correctness proof is to map the transformation into an axiomatized mathematical domain where formal (and automated) reasoning can be performed. This mapping is accomplished via an extended denotational semantic paradigm. In this approach, the abstract notion of a program state is distributed between an environment function and a store function. Such a distribution introduces properties that go beyond the abstract state that is being modeled. The reasoning framework needs to be aware of these properties in order to successfully complete a correctness proof. This papermore » discusses some of our experiences in proving the correctness of TAMPR transformations.« less

From sequencing to annotating: extending the metaphor of the book of life from genetics to genomics.

PubMed

Hellsten, Iina

2005-12-01

The article discusses how the metaphor of the Book of Life was extended over time to cover the life cycle of the Human Genome Project from genetics to genomics. In particular, the focus is on the role of extendable metaphors in the debate on the Human Genome Project in three European newspapers, popular scientific journals and scientific and scholarly articles from 1990 to 2002. In these different domains of use, various parts of the metaphor were highlighted. The metaphor of Book of Life was mainly used to justify the continuation of the gene research from gene sequencing to comparative genomics. Readily extendable metaphors, such as the Book of Life, function as useful communicative tools both over time and across domains of use.

Probing the Production of Amidated Peptides following Genetic and Dietary Copper Manipulations

PubMed Central

Yin, Ping; Bousquet-Moore, Danielle; Annangudi, Suresh P.; Southey, Bruce R.; Mains, Richard E.; Eipper, Betty A.; Sweedler, Jonathan V.

2011-01-01

Amidated neuropeptides play essential roles throughout the nervous and endocrine systems. Mice lacking peptidylglycine α-amidating monooxygenase (PAM), the only enzyme capable of producing amidated peptides, are not viable. In the amidation reaction, the reactant (glycine-extended peptide) is converted into a reaction intermediate (hydroxyglycine-extended peptide) by the copper-dependent peptidylglycine-α-hydroxylating monooxygenase (PHM) domain of PAM. The hydroxyglycine-extended peptide is then converted into amidated product by the peptidyl-α-hydroxyglycine α-amidating lyase (PAL) domain of PAM. PHM and PAL are stitched together in vertebrates, but separated in some invertebrates such as Drosophila and Hydra. In addition to its luminal catalytic domains, PAM includes a cytosolic domain that can enter the nucleus following release from the membrane by γ-secretase. In this work, several glycine- and hydroxyglycine-extended peptides as well as amidated peptides were qualitatively and quantitatively assessed from pituitaries of wild-type mice and mice with a single copy of the Pam gene (PAM+/−) via liquid chromatography-mass spectrometry-based methods. We provide the first evidence for the presence of a peptidyl-α-hydroxyglycine in vivo, indicating that the reaction intermediate becomes free and is not handed directly from PHM to PAL in vertebrates. Wild-type mice fed a copper deficient diet and PAM+/− mice exhibit similar behavioral deficits. While glycine-extended reaction intermediates accumulated in the PAM+/− mice and reflected dietary copper availability, amidated products were far more prevalent under the conditions examined, suggesting that the behavioral deficits observed do not simply reflect a lack of amidated peptides. PMID:22194882

Study of fault tolerant software technology for dynamic systems

NASA Technical Reports Server (NTRS)

Caglayan, A. K.; Zacharias, G. L.

1985-01-01

The major aim of this study is to investigate the feasibility of using systems-based failure detection isolation and compensation (FDIC) techniques in building fault-tolerant software and extending them, whenever possible, to the domain of software fault tolerance. First, it is shown that systems-based FDIC methods can be extended to develop software error detection techniques by using system models for software modules. In particular, it is demonstrated that systems-based FDIC techniques can yield consistency checks that are easier to implement than acceptance tests based on software specifications. Next, it is shown that systems-based failure compensation techniques can be generalized to the domain of software fault tolerance in developing software error recovery procedures. Finally, the feasibility of using fault-tolerant software in flight software is investigated. In particular, possible system and version instabilities, and functional performance degradation that may occur in N-Version programming applications to flight software are illustrated. Finally, a comparative analysis of N-Version and recovery block techniques in the context of generic blocks in flight software is presented.

Different functional modes of BAR domain proteins in formation and plasticity of mammalian postsynapses.

PubMed

Kessels, Michael M; Qualmann, Britta

2015-09-01

A plethora of cell biological processes involve modulations of cellular membranes. By using extended lipid-binding interfaces, some proteins have the power to shape membranes by attaching to them. Among such membrane shapers, the superfamily of Bin-Amphiphysin-Rvs (BAR) domain proteins has recently taken center stage. Extensive structural work on BAR domains has revealed a common curved fold that can serve as an extended membrane-binding interface to modulate membrane topologies and has allowed the grouping of the BAR domain superfamily into subfamilies with structurally slightly distinct BAR domain subtypes (N-BAR, BAR, F-BAR and I-BAR). Most BAR superfamily members are expressed in the mammalian nervous system. Neurons are elaborately shaped and highly compartmentalized cells. Therefore, analyses of synapse formation and of postsynaptic reorganization processes (synaptic plasticity) - a basis for learning and memory formation - has unveiled important physiological functions of BAR domain superfamily members. These recent advances, furthermore, have revealed that the functions of BAR domain proteins include different aspects. These functions are influenced by the often complex domain organization of BAR domain proteins. In this Commentary, we review these recent insights and propose to classify BAR domain protein functions into (1) membrane shaping, (2) physical integration, (3) action through signaling components, and (4) suppression of other BAR domain functions. © 2015. Published by The Company of Biologists Ltd.

Extended-range high-resolution dynamical downscaling over a continental-scale spatial domain with atmospheric and surface nudging

NASA Astrophysics Data System (ADS)

Husain, S. Z.; Separovic, L.; Yu, W.; Fernig, D.

2014-12-01

Extended-range high-resolution mesoscale simulations with limited-area atmospheric models when applied to downscale regional analysis fields over large spatial domains can provide valuable information for many applications including the weather-dependent renewable energy industry. Long-term simulations over a continental-scale spatial domain, however, require mechanisms to control the large-scale deviations in the high-resolution simulated fields from the coarse-resolution driving fields. As enforcement of the lateral boundary conditions is insufficient to restrict such deviations, large scales in the simulated high-resolution meteorological fields are therefore spectrally nudged toward the driving fields. Different spectral nudging approaches, including the appropriate nudging length scales as well as the vertical profiles and temporal relaxations for nudging, have been investigated to propose an optimal nudging strategy. Impacts of time-varying nudging and generation of hourly analysis estimates are explored to circumvent problems arising from the coarse temporal resolution of the regional analysis fields. Although controlling the evolution of the atmospheric large scales generally improves the outputs of high-resolution mesoscale simulations within the surface layer, the prognostically evolving surface fields can nevertheless deviate from their expected values leading to significant inaccuracies in the predicted surface layer meteorology. A forcing strategy based on grid nudging of the different surface fields, including surface temperature, soil moisture, and snow conditions, toward their expected values obtained from a high-resolution offline surface scheme is therefore proposed to limit any considerable deviation. Finally, wind speed and temperature at wind turbine hub height predicted by different spectrally nudged extended-range simulations are compared against observations to demonstrate possible improvements achievable using higher spatiotemporal resolution.

Conformational dynamics of bacterial trigger factor in apo and ribosome-bound states.

PubMed

Can, Mehmet Tarik; Kurkcuoglu, Zeynep; Ezeroglu, Gokce; Uyar, Arzu; Kurkcuoglu, Ozge; Doruker, Pemra

2017-01-01

The chaperone trigger factor (TF) binds to the ribosome exit tunnel and helps cotranslational folding of nascent chains (NC) in bacterial cells and chloroplasts. In this study, we aim to investigate the functional dynamics of fully-atomistic apo TF and its complex with 50S. As TF accomodates a high percentage of charged residues on its surface, the effect of ionic strength on TF dynamics is assessed here by performing five independent molecular dynamics (MD) simulations (total of 1.3 micro-second duration) at 29 mM and 150 mM ionic strengths. At both concentrations, TF exhibits high inter- and intra-domain flexibility related to its binding (BD), core (CD), and head (HD) domains. Even though large oscillations in gyration radius exist during each run, we do not detect the so-called 'fully collapsed' state with both HD and BD collapsed upon the core. In fact, the extended conformers with relatively open HD and BD are highly populated at the physiological concentration of 150 mM. More importantly, extended TF snapshots stand out in terms of favorable docking onto the 50S subunit. Elastic network modeling (ENM) indicates significant changes in TF's functional dynamics and domain decomposition depending on its conformation and positioning on the 50S. The most dominant slow motions are the lateral sweeping and vertical opening/closing of HD relative to 50S. Finally, our ENM-based efficient technique -ClustENM- is used to sample atomistic conformers starting with an extended TF-50S complex. Specifically, BD and CD motions are restricted near the tunnel exit, while HD is highly mobile. The atomistic conformers generated without an NC are in agreement with the cryo-EM maps available for TF-ribosome-NC complex.

The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility.

PubMed

Watanabe, Susan M; Simon, Viviana; Durham, Natasha D; Kemp, Brittney R; Machihara, Satoshi; Kemal, Kimdar Sherefa; Shi, Binshan; Foley, Brian; Li, Hongru; Chen, Benjamin K; Weiser, Barbara; Burger, Harold; Anastos, Kathryn; Chen, Chaoping; Carter, Carol A

2016-09-06

The p6 region of the HIV-1 structural precursor polyprotein, Gag, contains two motifs, P7TAP11 and L35YPLXSL41, designated as late (L) domain-1 and -2, respectively. These motifs bind the ESCRT-I factor Tsg101 and the ESCRT adaptor Alix, respectively, and are critical for efficient budding of virus particles from the plasma membrane. L domain-2 is thought to be functionally redundant to PTAP. To identify possible other functions of L domain-2, we examined this motif in dominant viruses that emerged in a group of 14 women who had detectable levels of HIV-1 in both plasma and genital tract despite a history of current or previous antiretroviral therapy. Remarkably, variants possessing mutations or rare polymorphisms in the highly conserved L domain-2 were identified in seven of these women. A mutation in a conserved residue (S40A) that does not reduce Gag interaction with Alix and therefore did not reduce budding efficiency was further investigated. This mutation causes a simultaneous change in the Pol reading frame but exhibits little deficiency in Gag processing and virion maturation. Whether introduced into the HIV-1 NL4-3 strain genome or a model protease (PR) precursor, S40A reduced production of mature PR. This same mutation also led to high level detection of two extended forms of PR that were fairly stable compared to the WT in the presence of IDV at various concentrations; one of the extended forms was effective in trans processing even at micromolar IDV. Our results indicate that L domain-2, considered redundant in vitro, can undergo mutations in vivo that significantly alter PR function. These may contribute fitness benefits in both the absence and presence of PR inhibitor.

Effects of head geometry simplifications on acoustic radiation of vowel sounds based on time-domain finite-element simulations.

PubMed

Arnela, Marc; Guasch, Oriol; Alías, Francesc

2013-10-01

One of the key effects to model in voice production is that of acoustic radiation of sound waves emanating from the mouth. The use of three-dimensional numerical simulations allows to naturally account for it, as well as to consider all geometrical head details, by extending the computational domain out of the vocal tract. Despite this advantage, many approximations to the head geometry are often performed for simplicity and impedance load models are still used as well to reduce the computational cost. In this work, the impact of some of these simplifications on radiation effects is examined for vowel production in the frequency range 0-10 kHz, by means of comparison with radiation from a realistic head. As a result, recommendations are given on their validity depending on whether high frequency energy (above 5 kHz) should be taken into account or not.

Dynamic control of magnetic nanowires by light-induced domain-wall kickoffs

NASA Astrophysics Data System (ADS)

Heintze, Eric; El Hallak, Fadi; Clauß, Conrad; Rettori, Angelo; Pini, Maria Gloria; Totti, Federico; Dressel, Martin; Bogani, Lapo

2013-03-01

Controlling the speed at which systems evolve is a challenge shared by all disciplines, and otherwise unrelated areas use common theoretical frameworks towards this goal. A particularly widespread model is Glauber dynamics, which describes the time evolution of the Ising model and can be applied to any binary system. Here we show, using molecular nanowires under irradiation, that Glauber dynamics can be controlled by a novel domain-wall kickoff mechanism. In contrast to known processes, the kickoff has unambiguous fingerprints, slowing down the spin-flip attempt rate by several orders of magnitude, and following a scaling law. The required irradiance is very low, a substantial improvement over present methods of magneto-optical switching. These results provide a new way to control and study stochastic dynamic processes. Being general for Glauber dynamics, they can be extended to different kinds of magnetic nanowires and to numerous fields, ranging from social evolution to neural networks and chemical reactivity.

Large-Eddy Simulation of Aeroacoustic Applications

NASA Technical Reports Server (NTRS)

Pruett, C. David; Sochacki, James S.

1999-01-01

This report summarizes work accomplished under a one-year NASA grant from NASA Langley Research Center (LaRC). The effort culminates three years of NASA-supported research under three consecutive one-year grants. The period of support was April 6, 1998, through April 5, 1999. By request, the grant period was extended at no-cost until October 6, 1999. Its predecessors have been directed toward adapting the numerical tool of large-eddy simulation (LES) to aeroacoustic applications, with particular focus on noise suppression in subsonic round jets. In LES, the filtered Navier-Stokes equations are solved numerically on a relatively coarse computational grid. Residual stresses, generated by scales of motion too small to be resolved on the coarse grid, are modeled. Although most LES incorporate spatial filtering, time-domain filtering affords certain conceptual and computational advantages, particularly for aeroacoustic applications. Consequently, this work has focused on the development of subgrid-scale (SGS) models that incorporate time-domain filters.

Internal Domains of Natural Porous Media Revealed: Critical Locations for Transport, Storage, and Chemical Reaction

DOE PAGES

Zachara, John; Brantley, Sue; Chorover, Jon; ...

2016-02-05

Internal pore domains exist within rocks, lithic fragments, subsurface sediments, and soil aggregates. These domains, termed internal domains in porous media (IDPM), represent a subset of a material’s porosity, contain a significant fraction of their porosity as nanopores, dominate the reactive surface area of diverse media types, and are important locations for chemical reactivity and fluid storage. IDPM are key features controlling hydrocarbon release from shales in hydraulic fracture systems, organic matter decomposition in soil, weathering and soil formation, and contaminant behavior in the vadose zone and groundwater. It is traditionally difficult to interrogate, advances in instrumentation and imaging methodsmore » are providing new insights on the physical structures and chemical attributes of IDPM, and their contributions to system behaviors. We discuss analytical methods to characterize IDPM, evaluate information on their size distributions, connectivity, and extended structures; determine whether they exhibit unique chemical reactivity; and assess the potential for their inclusion in reactive transport models. Moreover, ongoing developments in measurement technologies and sensitivity, and computer-assisted interpretation will improve understanding of these critical features in the future. Finally, impactful research opportunities exist to advance understanding of IDPM, and to incorporate their effects in reactive transport models for improved environmental simulation and prediction.« less

Dynamic Uncertain Causality Graph for Knowledge Representation and Reasoning: Utilization of Statistical Data and Domain Knowledge in Complex Cases.

PubMed

Zhang, Qin; Yao, Quanying

2018-05-01

The dynamic uncertain causality graph (DUCG) is a newly presented framework for uncertain causality representation and probabilistic reasoning. It has been successfully applied to online fault diagnoses of large, complex industrial systems, and decease diagnoses. This paper extends the DUCG to model more complex cases than what could be previously modeled, e.g., the case in which statistical data are in different groups with or without overlap, and some domain knowledge and actions (new variables with uncertain causalities) are introduced. In other words, this paper proposes to use -mode, -mode, and -mode of the DUCG to model such complex cases and then transform them into either the standard -mode or the standard -mode. In the former situation, if no directed cyclic graph is involved, the transformed result is simply a Bayesian network (BN), and existing inference methods for BNs can be applied. In the latter situation, an inference method based on the DUCG is proposed. Examples are provided to illustrate the methodology.

Quantitative theory of hydrophobic effect as a driving force of protein structure

PubMed Central

Perunov, Nikolay; England, Jeremy L

2014-01-01

Various studies suggest that the hydrophobic effect plays a major role in driving the folding of proteins. In the past, however, it has been challenging to translate this understanding into a predictive, quantitative theory of how the full pattern of sequence hydrophobicity in a protein shapes functionally important features of its tertiary structure. Here, we extend and apply such a phenomenological theory of the sequence-structure relationship in globular protein domains, which had previously been applied to the study of allosteric motion. In an effort to optimize parameters for the model, we first analyze the patterns of backbone burial found in single-domain crystal structures, and discover that classic hydrophobicity scales derived from bulk physicochemical properties of amino acids are already nearly optimal for prediction of burial using the model. Subsequently, we apply the model to studying structural fluctuations in proteins and establish a means of identifying ligand-binding and protein–protein interaction sites using this approach. PMID:24408023

Numerical Simulations of a Multiscale Model of Stratified Langmuir Circulation

NASA Astrophysics Data System (ADS)

Malecha, Ziemowit; Chini, Gregory; Julien, Keith

2012-11-01

Langmuir circulation (LC), a prominent form of wind and surface-wave driven shear turbulence in the ocean surface boundary layer (BL), is commonly modeled using the Craik-Leibovich (CL) equations, a phase-averaged variant of the Navier-Stokes (NS) equations. Although surface-wave filtering renders the CL equations more amenable to simulation than are the instantaneous NS equations, simulations in wide domains, hundreds of times the BL depth, currently earn the ``grand challenge'' designation. To facilitate simulations of LC in such spatially-extended domains, we have derived multiscale CL equations by exploiting the scale separation between submesoscale and BL flows in the upper ocean. The numerical algorithm for simulating this multiscale model resembles super-parameterization schemes used in meteorology, but retains a firm mathematical basis. We have validated our algorithm and here use it to perform multiscale simulations of the interaction between LC and upper ocean density stratification. ZMM, GPC, KJ gratefully acknowledge funding from NSF CMG Award 0934827.

Optimising predictor domains for spatially coherent precipitation downscaling

NASA Astrophysics Data System (ADS)

Radanovics, S.; Vidal, J.-P.; Sauquet, E.; Ben Daoud, A.; Bontron, G.

2013-10-01

Statistical downscaling is widely used to overcome the scale gap between predictors from numerical weather prediction models or global circulation models and predictands like local precipitation, required for example for medium-term operational forecasts or climate change impact studies. The predictors are considered over a given spatial domain which is rarely optimised with respect to the target predictand location. In this study, an extended version of the growing rectangular domain algorithm is proposed to provide an ensemble of near-optimum predictor domains for a statistical downscaling method. This algorithm is applied to find five-member ensembles of near-optimum geopotential predictor domains for an analogue downscaling method for 608 individual target zones covering France. Results first show that very similar downscaling performances based on the continuous ranked probability score (CRPS) can be achieved by different predictor domains for any specific target zone, demonstrating the need for considering alternative domains in this context of high equifinality. A second result is the large diversity of optimised predictor domains over the country that questions the commonly made hypothesis of a common predictor domain for large areas. The domain centres are mainly distributed following the geographical location of the target location, but there are apparent differences between the windward and the lee side of mountain ridges. Moreover, domains for target zones located in southeastern France are centred more east and south than the ones for target locations on the same longitude. The size of the optimised domains tends to be larger in the southeastern part of the country, while domains with a very small meridional extent can be found in an east-west band around 47° N. Sensitivity experiments finally show that results are rather insensitive to the starting point of the optimisation algorithm except for zones located in the transition area north of this east-west band. Results also appear generally robust with respect to the archive length considered for the analogue method, except for zones with high interannual variability like in the Cévennes area. This study paves the way for defining regions with homogeneous geopotential predictor domains for precipitation downscaling over France, and therefore de facto ensuring the spatial coherence required for hydrological applications.

Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

NASA Astrophysics Data System (ADS)

Zirak, P.; Penzkofer, A.; Hegemann, P.; Mathes, T.

2007-05-01

The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ( τrec ≈ 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be ϕs ≈ 0.3 (for AppA-wt: ϕs ≈ 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

What is eHealth (6)? Development of a Conceptual Model for eHealth: Qualitative Study with Key Informants

PubMed Central

Janssen, Anna; Barnet, Stewart

2017-01-01

Background Despite rapid growth in eHealth research, there remains a lack of consistency in defining and using terms related to eHealth. More widely cited definitions provide broad understanding of eHealth but lack sufficient conceptual clarity to operationalize eHealth and enable its implementation in health care practice, research, education, and policy. Definitions that are more detailed are often context or discipline specific, limiting ease of translation of these definitions across the breadth of eHealth perspectives and situations. A conceptual model of eHealth that adequately captures its complexity and potential overlaps is required. This model must also be sufficiently detailed to enable eHealth operationalization and hypothesis testing. Objective This study aimed to develop a conceptual practice-based model of eHealth to support health professionals in applying eHealth to their particular professional or discipline contexts. Methods We conducted semistructured interviews with key informants (N=25) from organizations involved in health care delivery, research, education, practice, governance, and policy to explore their perspectives on and experiences with eHealth. We used purposeful sampling for maximum diversity. Interviews were coded and thematically analyzed for emergent domains. Results Thematic analyses revealed 3 prominent but overlapping domains of eHealth: (1) health in our hands (using eHealth technologies to monitor, track, and inform health), (2) interacting for health (using digital technologies to enable health communication among practitioners and between health professionals and clients or patients), and (3) data enabling health (collecting, managing, and using health data). These domains formed a model of eHealth that addresses the need for clear definitions and a taxonomy of eHealth while acknowledging the fluidity of this area and the strengths of initiatives that span multiple eHealth domains. Conclusions This model extends current understanding of eHealth by providing clearly defined domains of eHealth while highlighting the benefits of using digital technologies in ways that cross several domains. It provides the depth of perspectives and examples of eHealth use that are lacking in previous research. On the basis of this model, we suggest that eHealth initiatives that are most impactful would include elements from all 3 domains. PMID:29066429

What is eHealth (6)? Development of a Conceptual Model for eHealth: Qualitative Study with Key Informants.

PubMed

Shaw, Tim; McGregor, Deborah; Brunner, Melissa; Keep, Melanie; Janssen, Anna; Barnet, Stewart

2017-10-24

Despite rapid growth in eHealth research, there remains a lack of consistency in defining and using terms related to eHealth. More widely cited definitions provide broad understanding of eHealth but lack sufficient conceptual clarity to operationalize eHealth and enable its implementation in health care practice, research, education, and policy. Definitions that are more detailed are often context or discipline specific, limiting ease of translation of these definitions across the breadth of eHealth perspectives and situations. A conceptual model of eHealth that adequately captures its complexity and potential overlaps is required. This model must also be sufficiently detailed to enable eHealth operationalization and hypothesis testing. This study aimed to develop a conceptual practice-based model of eHealth to support health professionals in applying eHealth to their particular professional or discipline contexts. We conducted semistructured interviews with key informants (N=25) from organizations involved in health care delivery, research, education, practice, governance, and policy to explore their perspectives on and experiences with eHealth. We used purposeful sampling for maximum diversity. Interviews were coded and thematically analyzed for emergent domains. Thematic analyses revealed 3 prominent but overlapping domains of eHealth: (1) health in our hands (using eHealth technologies to monitor, track, and inform health), (2) interacting for health (using digital technologies to enable health communication among practitioners and between health professionals and clients or patients), and (3) data enabling health (collecting, managing, and using health data). These domains formed a model of eHealth that addresses the need for clear definitions and a taxonomy of eHealth while acknowledging the fluidity of this area and the strengths of initiatives that span multiple eHealth domains. This model extends current understanding of eHealth by providing clearly defined domains of eHealth while highlighting the benefits of using digital technologies in ways that cross several domains. It provides the depth of perspectives and examples of eHealth use that are lacking in previous research. On the basis of this model, we suggest that eHealth initiatives that are most impactful would include elements from all 3 domains. ©Tim Shaw, Deborah McGregor, Melissa Brunner, Melanie Keep, Anna Janssen, Stewart Barnet. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.10.2017.

Discrete models for the numerical analysis of time-dependent multidimensional gas dynamics

NASA Technical Reports Server (NTRS)

Roe, P. L.

1984-01-01

A possible technique is explored for extending to multidimensional flows some of the upwind-differencing methods that are highly successful in the one-dimensional case. Emphasis is on the two-dimensional case, and the flow domain is assumed to be divided into polygonal computational elements. Inside each element, the flow is represented by a local superposition of elementary solutions consisting of plane waves not necessarily aligned with the element boundaries.

Extended output phasor representation of multi-spectral fluorescence lifetime imaging microscopy

PubMed Central

Campos-Delgado, Daniel U.; Navarro, O. Gutiérrez; Arce-Santana, E. R.; Jo, Javier A.

2015-01-01

In this paper, we investigate novel low-dimensional and model-free representations for multi-spectral fluorescence lifetime imaging microscopy (m-FLIM) data. We depart from the classical definition of the phasor in the complex plane to propose the extended output phasor (EOP) and extended phasor (EP) for multi-spectral information. The frequency domain properties of the EOP and EP are analytically studied based on a multiexponential model for the impulse response of the imaged tissue. For practical implementations, the EOP is more appealing since there is no need to perform deconvolution of the instrument response from the measured m-FLIM data, as in the case of EP. Our synthetic and experimental evaluations with m-FLIM datasets of human coronary atherosclerotic plaques show that low frequency indexes have to be employed for a distinctive representation of the EOP and EP, and to reduce noise distortion. The tissue classification of the m-FLIM datasets by EOP and EP also improves with low frequency indexes, and does not present significant differences by using either phasor. PMID:26114031

Factor VIII Interacts with the Endocytic Receptor Low-density Lipoprotein Receptor-related Protein 1 via an Extended Surface Comprising "Hot-Spot" Lysine Residues.

PubMed

van den Biggelaar, Maartje; Madsen, Jesper J; Faber, Johan H; Zuurveld, Marleen G; van der Zwaan, Carmen; Olsen, Ole H; Stennicke, Henning R; Mertens, Koen; Meijer, Alexander B

2015-07-03

Lysine residues are implicated in driving the ligand binding to the LDL receptor family. However, it has remained unclear how specificity is regulated. Using coagulation factor VIII as a model ligand, we now study the contribution of individual lysine residues in the interaction with the largest member of the LDL receptor family, low-density lipoprotein receptor-related protein (LRP1). Using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and SPR interaction analysis on a library of lysine replacement variants as two independent approaches, we demonstrate that the interaction between factor VIII (FVIII) and LRP1 occurs over an extended surface containing multiple lysine residues. None of the individual lysine residues account completely for LRP1 binding, suggesting an additive binding model. Together with structural docking studies, our data suggest that FVIII interacts with LRP1 via an extended surface of multiple lysine residues that starts at the bottom of the C1 domain and winds around the FVIII molecule. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass.

PubMed

Mercken, Evi M; Mitchell, Sarah J; Martin-Montalvo, Alejandro; Minor, Robin K; Almeida, Maria; Gomes, Ana P; Scheibye-Knudsen, Morten; Palacios, Hector H; Licata, Jordan J; Zhang, Yongqing; Becker, Kevin G; Khraiwesh, Husam; González-Reyes, José A; Villalba, José M; Baur, Joseph A; Elliott, Peter; Westphal, Christoph; Vlasuk, George P; Ellis, James L; Sinclair, David A; Bernier, Michel; de Cabo, Rafael

2014-10-01

Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Combined feedforward and model-assisted active disturbance rejection control for non-minimum phase system.

PubMed

Sun, Li; Li, Donghai; Gao, Zhiqiang; Yang, Zhao; Zhao, Shen

2016-09-01

Control of the non-minimum phase (NMP) system is challenging, especially in the presence of modelling uncertainties and external disturbances. To this end, this paper presents a combined feedforward and model-assisted Active Disturbance Rejection Control (MADRC) strategy. Based on the nominal model, the feedforward controller is used to produce a tracking performance that has minimum settling time subject to a prescribed undershoot constraint. On the other hand, the unknown disturbances and uncertain dynamics beyond the nominal model are compensated by MADRC. Since the conventional Extended State Observer (ESO) is not suitable for the NMP system, a model-assisted ESO (MESO) is proposed based on the nominal observable canonical form. The convergence of MESO is proved in time domain. The stability, steady-state characteristics and robustness of the closed-loop system are analyzed in frequency domain. The proposed strategy has only one tuning parameter, i.e., the bandwidth of MESO, which can be readily determined with a prescribed robustness level. Some comparative examples are given to show the efficacy of the proposed method. This paper depicts a promising prospect of the model-assisted ADRC in dealing with complex systems. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

A Short Note on Rules and Higher Order Rules.

ERIC Educational Resources Information Center

Scandura, Joseph M.

This brief paper argues that structural analysis--an extended form of cognitive task analysis--demonstrates that both domain dependent and domain independent knowledge can be derived from specific content domains. It is noted that the major difference between the two is that lower order rules (specific knowledge) are derived directly from specific…

Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher,R.; Chung, H.; Zhai, Q.

2007-01-01

ALIX/AIP1 functions in enveloped virus budding, endosomal protein sorting, and many other cellular processes. Retroviruses, including HIV-1, SIV, and EIAV, bind and recruit ALIX through YPXnL late-domain motifs (X = any residue; n = 1-3). Crystal structures reveal that human ALIX is composed of an N-terminal Bro1 domain and a central domain that is composed of two extended three-helix bundles that form elongated arms that fold back into a 'V.'. The structures also reveal conformational flexibility in the arms that suggests that the V domain may act as a flexible hinge in response to ligand binding. YPXnL late domains bindmore » in a conserved hydrophobic pocket on the second arm near the apex of the V, whereas CHMP4/ESCRT-III proteins bind a conserved hydrophobic patch on the Bro1 domain, and both interactions are required for virus budding. ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery.« less

Skierarchy: Extending the Power of Crowdsourcing Using a Hierarchy of Domain Experts, Crowd and Machine Learning

DTIC Science & Technology

2012-11-01

college background and good reading comprehension skills in English, and bring to them to the office space to work for us full-time on micro-tasks. This...reasonable reading comprehension skills in English. The expert spent only 1/3rd the time as each member of the crowd in the entire annotation process...3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Skierarchy: Extending the Power of Crowdsourcing Using a Hierarchy of Domain

Keep Using My Health Apps: Discover Users' Perception of Health and Fitness Apps with the UTAUT2 Model.

PubMed

Yuan, Shupei; Ma, Wenjuan; Kanthawala, Shaheen; Peng, Wei

2015-09-01

Health and fitness applications (apps) are one of the major app categories in the current mobile app market. Few studies have examined this area from the users' perspective. This study adopted the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) Model to examine the predictors of the users' intention to adopt health and fitness apps. A survey (n=317) was conducted with college-aged smartphone users at a Midwestern university in the United States. Performance expectancy, hedonic motivations, price value, and habit were significant predictors of users' intention of continued usage of health and fitness apps. However, effort expectancy, social influence, and facilitating conditions were not found to predict users' intention of continued usage of health and fitness apps. This study extends the UTATU2 Model to the mobile apps domain and provides health professions, app designers, and marketers with the insights of user experience in terms of continuously using health and fitness apps.

Columnar organization of orientation domains in V1

NASA Astrophysics Data System (ADS)

Liedtke, Joscha; Wolf, Fred

In the primary visual cortex (V1) of primates and carnivores, the functional architecture of basic stimulus selectivities appears similar across cortical layers (Hubel & Wiesel, 1962) justifying the use of two-dimensional cortical models and disregarding organization in the third dimension. Here we show theoretically that already small deviations from an exact columnar organization lead to non-trivial three-dimensional functional structures. We extend two-dimensional random field models (Schnabel et al., 2007) to a three-dimensional cortex by keeping a typical scale in each layer and introducing a correlation length in the third, columnar dimension. We examine in detail the three-dimensional functional architecture for different cortical geometries with different columnar correlation lengths. We find that (i) topological defect lines are generally curved and (ii) for large cortical curvatures closed loops and reconnecting topological defect lines appear. This theory extends the class of random field models by introducing a columnar dimension and provides a systematic statistical assessment of the three-dimensional functional architecture of V1 (see also (Tanaka et al., 2011)).

Augmenting Probabilistic Risk Assesment with Malevolent Initiators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curtis Smith; David Schwieder

2011-11-01

As commonly practiced, the use of probabilistic risk assessment (PRA) in nuclear power plants only considers accident initiators such as natural hazards, equipment failures, and human error. Malevolent initiators are ignored in PRA, but are considered the domain of physical security, which uses vulnerability assessment based on an officially specified threat (design basis threat). This paper explores the implications of augmenting and extending existing PRA models by considering new and modified scenarios resulting from malevolent initiators. Teaming the augmented PRA models with conventional vulnerability assessments can cost-effectively enhance security of a nuclear power plant. This methodology is useful for operatingmore » plants, as well as in the design of new plants. For the methodology, we have proposed an approach that builds on and extends the practice of PRA for nuclear power plants for security-related issues. Rather than only considering 'random' failures, we demonstrated a framework that is able to represent and model malevolent initiating events and associated plant impacts.« less

Optical-domain subsampling for data efficient depth ranging in Fourier-domain optical coherence tomography

PubMed Central

Siddiqui, Meena; Vakoc, Benjamin J.

2012-01-01

Recent advances in optical coherence tomography (OCT) have led to higher-speed sources that support imaging over longer depth ranges. Limitations in the bandwidth of state-of-the-art acquisition electronics, however, prevent adoption of these advances into the clinical applications. Here, we introduce optical-domain subsampling as a method for imaging at high-speeds and over extended depth ranges but with a lower acquisition bandwidth than that required using conventional approaches. Optically subsampled laser sources utilize a discrete set of wavelengths to alias fringe signals along an extended depth range into a bandwidth limited frequency window. By detecting the complex fringe signals and under the assumption of a depth-constrained signal, optical-domain subsampling enables recovery of the depth-resolved scattering signal without overlapping artifacts from this bandwidth-limited window. We highlight key principles behind optical-domain subsampled imaging, and demonstrate this principle experimentally using a polygon-filter based swept-source laser that includes an intra-cavity Fabry-Perot (FP) etalon. PMID:23038343

Global Environmental Multiscale model - a platform for integrated environmental predictions

NASA Astrophysics Data System (ADS)

Kaminski, Jacek W.; Struzewska, Joanna; Neary, Lori; Dearden, Frank

2017-04-01

The Global Environmental Multiscale model was developed by the Government of Canada as an operational weather prediction model in the mid-1990s. Subsequently, it was used as the host meteorological model for an on-line implementation of air quality chemistry and aerosols from global to the meso-gamma scale. Further model developments led to the vertical extension of the modelling domain to include stratospheric chemistry, aerosols, and formation of polar stratospheric clouds. In parallel, the modelling platform was used for planetary applications where dynamical, radiative transfer and chemical processes in the atmosphere of Mars were successfully simulated. Undoubtedly, the developed modelling platform can be classified as an example capable of the seamless and coupled modelling of the dynamics and chemistry of planetary atmospheres. We will present modelling results for global, regional, and local air quality episodes and the long-term air quality trends. Upper troposphere and lower stratosphere modelling results will be presented in terms of climate change and subsonic aviation emissions modelling. Model results for the atmosphere of Mars will be presented in the context of the 2016 ExoMars mission and the anticipated observations from the NOMAD instrument. Also, we will present plans and the design to extend the GEM model to the F region with further coupling with a magnetospheric model that extends to 15 Re.

The challenge of annotating protein sequences: The tale of eight domains of unknown function in Pfam.

PubMed

Goonesekere, Nalin C W; Shipely, Krysten; O'Connor, Kevin

2010-06-01

The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families. However, a subset of these families, known as domains of unknown function (DUFs), remains poorly characterized. We have related sequences from DUF404, DUF407, DUF482, DUF608, DUF810, DUF853, DUF976 and DUF1111 to homologs in PDB, within the midnight zone (9-20%) of sequence identity. These relationships were extended to provide functional annotation by sequence analysis and model building. Also described are examples of residue plasticity within enzyme active sites, and change of function within homologous sequences of a DUF. Copyright 2010 Elsevier Ltd. All rights reserved.

Thermodynamic constraints on fluctuation phenomena

NASA Astrophysics Data System (ADS)

Maroney, O. J. E.

2009-12-01

The relationships among reversible Carnot cycles, the absence of perpetual motion machines, and the existence of a nondecreasing globally unique entropy function form the starting point of many textbook presentations of the foundations of thermodynamics. However, the thermal fluctuation phenomena associated with statistical mechanics has been argued to restrict the domain of validity of this basis of the second law of thermodynamics. Here we demonstrate that fluctuation phenomena can be incorporated into the traditional presentation, extending rather than restricting the domain of validity of the phenomenologically motivated second law. Consistency conditions lead to constraints upon the possible spectrum of thermal fluctuations. In a special case this uniquely selects the Gibbs canonical distribution and more generally incorporates the Tsallis distributions. No particular model of microscopic dynamics need be assumed.

Thermodynamic constraints on fluctuation phenomena.

PubMed

Maroney, O J E

2009-12-01

The relationships among reversible Carnot cycles, the absence of perpetual motion machines, and the existence of a nondecreasing globally unique entropy function form the starting point of many textbook presentations of the foundations of thermodynamics. However, the thermal fluctuation phenomena associated with statistical mechanics has been argued to restrict the domain of validity of this basis of the second law of thermodynamics. Here we demonstrate that fluctuation phenomena can be incorporated into the traditional presentation, extending rather than restricting the domain of validity of the phenomenologically motivated second law. Consistency conditions lead to constraints upon the possible spectrum of thermal fluctuations. In a special case this uniquely selects the Gibbs canonical distribution and more generally incorporates the Tsallis distributions. No particular model of microscopic dynamics need be assumed.

Kalman filter estimation of human pilot-model parameters

NASA Technical Reports Server (NTRS)

Schiess, J. R.; Roland, V. R.

1975-01-01

The parameters of a human pilot-model transfer function are estimated by applying the extended Kalman filter to the corresponding retarded differential-difference equations in the time domain. Use of computer-generated data indicates that most of the parameters, including the implicit time delay, may be reasonably estimated in this way. When applied to two sets of experimental data obtained from a closed-loop tracking task performed by a human, the Kalman filter generated diverging residuals for one of the measurement types, apparently because of model assumption errors. Application of a modified adaptive technique was found to overcome the divergence and to produce reasonable estimates of most of the parameters.

A general structure-property relationship to predict the enthalpy of vaporisation at ambient temperatures.

PubMed

Oberg, T

2007-01-01

The vapour pressure is the most important property of an anthropogenic organic compound in determining its partitioning between the atmosphere and the other environmental media. The enthalpy of vaporisation quantifies the temperature dependence of the vapour pressure and its value around 298 K is needed for environmental modelling. The enthalpy of vaporisation can be determined by different experimental methods, but estimation methods are needed to extend the current database and several approaches are available from the literature. However, these methods have limitations, such as a need for other experimental results as input data, a limited applicability domain, a lack of domain definition, and a lack of predictive validation. Here we have attempted to develop a quantitative structure-property relationship (QSPR) that has general applicability and is thoroughly validated. Enthalpies of vaporisation at 298 K were collected from the literature for 1835 pure compounds. The three-dimensional (3D) structures were optimised and each compound was described by a set of computationally derived descriptors. The compounds were randomly assigned into a calibration set and a prediction set. Partial least squares regression (PLSR) was used to estimate a low-dimensional QSPR model with 12 latent variables. The predictive performance of this model, within the domain of application, was estimated at n=560, q2Ext=0.968 and s=0.028 (log transformed values). The QSPR model was subsequently applied to a database of 100,000+ structures, after a similar 3D optimisation and descriptor generation. Reliable predictions can be reported for compounds within the previously defined applicability domain.

Biological and artificial cognition: what can we learn about mechanisms by modelling physical cognition problems using artificial intelligence planning techniques?

PubMed Central

Chappell, Jackie; Hawes, Nick

2012-01-01

Do we fully understand the structure of the problems we present to our subjects in experiments on animal cognition, and the information required to solve them? While we currently have a good understanding of the behavioural and neurobiological mechanisms underlying associative learning processes, we understand much less about the mechanisms underlying more complex forms of cognition in animals. In this study, we present a proposal for a new way of thinking about animal cognition experiments. We describe a process in which a physical cognition task domain can be decomposed into its component parts, and models constructed to represent both the causal events of the domain and the information available to the agent. We then implement a simple set of models, using the planning language MAPL within the MAPSIM simulation environment, and applying it to a puzzle tube task previously presented to orangutans. We discuss the results of the models and compare them with the results from the experiments with orangutans, describing the advantages of this approach, and the ways in which it could be extended. PMID:22927571

Biological and artificial cognition: what can we learn about mechanisms by modelling physical cognition problems using artificial intelligence planning techniques?

PubMed

Chappell, Jackie; Hawes, Nick

2012-10-05

Do we fully understand the structure of the problems we present to our subjects in experiments on animal cognition, and the information required to solve them? While we currently have a good understanding of the behavioural and neurobiological mechanisms underlying associative learning processes, we understand much less about the mechanisms underlying more complex forms of cognition in animals. In this study, we present a proposal for a new way of thinking about animal cognition experiments. We describe a process in which a physical cognition task domain can be decomposed into its component parts, and models constructed to represent both the causal events of the domain and the information available to the agent. We then implement a simple set of models, using the planning language MAPL within the MAPSIM simulation environment, and applying it to a puzzle tube task previously presented to orangutans. We discuss the results of the models and compare them with the results from the experiments with orangutans, describing the advantages of this approach, and the ways in which it could be extended.

Cognitive Performance in Older Adults with Stable Heart Failure: Longitudinal Evidence for Stability and Improvement

PubMed Central

Alosco, Michael L.; Garcia, Sarah; Spitznagel, Mary Beth; van Dulmen, Manfred; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

2013-01-01

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. PMID:23906182

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

DOE PAGES

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany; ...

2017-01-31

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less

Generic Safety Requirements for Developing Safe Insulin Pump Software

PubMed Central

Zhang, Yi; Jetley, Raoul; Jones, Paul L; Ray, Arnab

2011-01-01

Background The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community. Methods In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article. Results Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance. Conclusions We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving overall safety of insulin pump software. PMID:22226258

The effects of the WISE/ GALEX photometry for the SED-fitting with M31 star clusters and candidates

NASA Astrophysics Data System (ADS)

Fan, Zhou; Wang, Song

2017-10-01

Spectral energy distribution (SED) fitting of stellar population synthesis models is an important and popular way to constrain the physical parameters—e.g., the ages, metallicities, masses for stellar population analysis. The previous works suggest that both blue-bands and red-bands photometry works for the SED-fitting. Either blue-domained or red-domained SED-fitting usually lead to the unreliable or biased results. Meanwhile, it seems that extending the wavelength coverage could be helpful. Since the Galaxy Evolution Explorer ( GALEX) and Wide-field Infrared Survey Explorer (WISE) provide the FUV/NUV and mid-infrared W1/W2 band data, we extend the SED-fitting to a wider wavelength coverage. In our work, we analyzed the effect of adding the FUV/NUV and W1/W2 band to the optical and near-infrared UBVRIJHK bands for the fitting with the (Bruzual and Charlot in Mon. Not. R. Astron. Soc. 344, 1000, 2003) (BC03) models and galev models. It is found that the FUV/NUV bands data affect the fitting results of both ages and metallicities much more significantly than that of the WISE W1/W2 band with the BC03 models. While for the galev models, the effect of the WISE W1/W2 band for the metallicity fitting seems comparable to that of GALEX FUV/NUV bands, but for age the effect of the W1/W2 band seems less crucial than that of the FUV/NUV bands. Thus we conclude that the GALEX FUV/NUV bands are more crucial for the SED-fitting of ages and metallicities, than the other bands, and the high-quality UV data (with high photometry precision) are required.

Tectono-sedimentary evolution of the eastern Gulf of Aden conjugate passive margins: Narrowness and asymmetry in oblique rifting context

NASA Astrophysics Data System (ADS)

Nonn, Chloé; Leroy, Sylvie; Khanbari, Khaled; Ahmed, Abdulhakim

2017-11-01

Here, we focus on the yet unexplored eastern Gulf of Aden, on Socotra Island (Yemen), Southeastern Oman and offshore conjugate passive margins between the Socotra-Hadbeen (SHFZ) and the eastern Gulf of Aden fracture zones. Our interpretation leads to onshore-offshore stratigraphic correlation between the passive margins. We present a new map reflecting the boundaries between the crustal domains (proximal, necking, hyper-extended, exhumed mantle, proto-oceanic and oceanic domains) and structures using bathymetry, magnetic surveys and seismic reflection data. The most striking result is that the magma-poor conjugate margins exhibit asymmetrical architecture since the thinning phase (Upper Rupelian-Burdigalian). Their necking domains are sharp ( 40-10 km wide) and their hyper-extended domains are narrow and asymmetric ( 10-40 km wide on the Socotra margin and 50-80 km wide on the Omani margin). We suggest that this asymmetry is related to the migration of the rift center producing significant lower crustal flow and sequential faulting in the hyper-extended domain. Throughout the Oligo-Miocene rifting, far-field forces dominate and the deformation is accommodated along EW to N110°E northward-dipping low angle normal faults. Convection in the mantle near the SHFZ may be responsible of change in fault dip polarity in the Omani hyper-extended domain. We show the existence of a northward-dipping detachment fault formed at the beginning of the exhumation phase (Burdigalien). It separates the northern upper plate (Oman) from southern lower plate (Socotra Island) and may have generated rift-induced decompression melting and volcanism affecting the upper plate. We highlight multiple generations of detachment faults exhuming serpentinized subcontinental mantle in the ocean-continent transition. Associated to significant decompression melting, final detachment fault may have triggered the formation of a proto-oceanic crust at 17.6 Ma and induced late volcanism up to 10 Ma. Finally, the setting up of a steady-state oceanic spreading center occurs at 17 Ma.

The role of parents in the ontogeny of achievement-related motivation and behavioral choices.

PubMed

Simpkins, Sandra D

2015-06-01

Parents believe what they do matters. But, how does it matter? How do parents' beliefs about their children early on translate into the choices those children make as adolescents? The Eccles' expectancy–value model asserts that parents' beliefs about their children during childhood predict adolescents' achievement-related choices through a sequence of processes that operate in a cumulative, cascading fashion over time. Specifically, parents' beliefs predict parents' behaviors that predict their children's motivational beliefs. Those beliefs predict children's subsequent choices. Using data from the Childhood and Beyond Study (92% European American; N = 723), we tested these predictions in the activity domains of sports, instrumental music, mathematics, and reading across a 12-year period. In testing these predictions, we looked closely at the idea of reciprocal influences and at the role of child gender as a moderator. The cross-lagged models generally supported the bidirectional influences described in Eccles' expectancy-value model. Furthermore, the findings demonstrated that: (a) these relations were stronger in the leisure domains than in the academic domains, (b) these relations did not consistently vary based on youth gender, (c) parents were stronger predictors of their children's beliefs than vice versa, and (d) adolescents' beliefs were stronger predictors of their behaviors than the reverse. The findings presented in this monograph extend our understanding of the complexity of families, developmental processes that unfold over time, and the extent to which these processes are universal across domains and child gender.

Cross-correlation least-squares reverse time migration in the pseudo-time domain

NASA Astrophysics Data System (ADS)

Li, Qingyang; Huang, Jianping; Li, Zhenchun

2017-08-01

The least-squares reverse time migration (LSRTM) method with higher image resolution and amplitude is becoming increasingly popular. However, the LSRTM is not widely used in field land data processing because of its sensitivity to the initial migration velocity model, large computational cost and mismatch of amplitudes between the synthetic and observed data. To overcome the shortcomings of the conventional LSRTM, we propose a cross-correlation least-squares reverse time migration algorithm in pseudo-time domain (PTCLSRTM). Our algorithm not only reduces the depth/velocity ambiguities, but also reduces the effect of velocity error on the imaging results. It relieves the accuracy requirements on the migration velocity model of least-squares migration (LSM). The pseudo-time domain algorithm eliminates the irregular wavelength sampling in the vertical direction, thus it can reduce the vertical grid points and memory requirements used during computation, which makes our method more computationally efficient than the standard implementation. Besides, for field data applications, matching the recorded amplitudes is a very difficult task because of the viscoelastic nature of the Earth and inaccuracies in the estimation of the source wavelet. To relax the requirement for strong amplitude matching of LSM, we extend the normalized cross-correlation objective function to the pseudo-time domain. Our method is only sensitive to the similarity between the predicted and the observed data. Numerical tests on synthetic and land field data confirm the effectiveness of our method and its adaptability for complex models.

SynechoNET: integrated protein-protein interaction database of a model cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Kim, Woo-Yeon; Kang, Sungsoo; Kim, Byoung-Chul; Oh, Jeehyun; Cho, Seongwoong; Bhak, Jong; Choi, Jong-Soon

2008-01-01

Cyanobacteria are model organisms for studying photosynthesis, carbon and nitrogen assimilation, evolution of plant plastids, and adaptability to environmental stresses. Despite many studies on cyanobacteria, there is no web-based database of their regulatory and signaling protein-protein interaction networks to date. We report a database and website SynechoNET that provides predicted protein-protein interactions. SynechoNET shows cyanobacterial domain-domain interactions as well as their protein-level interactions using the model cyanobacterium, Synechocystis sp. PCC 6803. It predicts the protein-protein interactions using public interaction databases that contain mutually complementary and redundant data. Furthermore, SynechoNET provides information on transmembrane topology, signal peptide, and domain structure in order to support the analysis of regulatory membrane proteins. Such biological information can be queried and visualized in user-friendly web interfaces that include the interactive network viewer and search pages by keyword and functional category. SynechoNET is an integrated protein-protein interaction database designed to analyze regulatory membrane proteins in cyanobacteria. It provides a platform for biologists to extend the genomic data of cyanobacteria by predicting interaction partners, membrane association, and membrane topology of Synechocystis proteins. SynechoNET is freely available at http://synechocystis.org/ or directly at http://bioportal.kobic.kr/SynechoNET/.

Exploration of interaction zones of β-tubulin colchicine binding domain of helminths and binding mechanism of anthelmintics.

PubMed

Ranjan, Prabodh; Kumar, Sivakumar Prasanth; Kari, Vijayakrishna; Jha, Prakash Chandra

2017-06-01

Numerous studies postulated the possible modes of anthelmintic activity by targeting alternate or extended regions of colchicine binding domain of helminth β-tubulin. We present three interaction zones (zones vide -1 to -3) in the colchicine binding domain of Haemonchus contortus (a helminth) β-tubulin homology model and developed zone-wise structure-based pharmacophore models coupled with molecular docking technique to unveil the binding hypotheses. The resulted ten structure-based hypotheses were then refined to essential three point pharmacophore features that captured recurring and crucial non-covalent receptor contacts and proposed three characteristics necessary for optimal zone-2 binding: a conserved pair of H bond acceptor (HBA to form H bond with Asn226 residue) and an aliphatic moiety of molecule separated by 3.75±0.44Å. Further, an aliphatic or a heterocyclic group distant (11.75±1.14Å) to the conserved aliphatic site formed the third feature component in the zone-2 specific anthelmintic pharmacophore model. Alternatively, an additional HBA can be substituted as a third component to establish H bonding with Asn204. We discern that selective zone-2 anthelmintics can be designed effectively by closely adapting the pharmacophore feature patterns and its geometrical constraints. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

PubMed

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Low Resolution Solution Structure of HAMLET and the Importance of Its Alpha-Domains in Tumoricidal Activity

PubMed Central

Ho CS, James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells. PMID:23300861

Multiclass Continuous Correspondence Learning

NASA Technical Reports Server (NTRS)

Bue, Brian D,; Thompson, David R.

2011-01-01

We extend the Structural Correspondence Learning (SCL) domain adaptation algorithm of Blitzer er al. to the realm of continuous signals. Given a set of labeled examples belonging to a 'source' domain, we select a set of unlabeled examples in a related 'target' domain that play similar roles in both domains. Using these 'pivot samples, we map both domains into a common feature space, allowing us to adapt a classifier trained on source examples to classify target examples. We show that when between-class distances are relatively preserved across domains, we can automatically select target pivots to bring the domains into correspondence.

Extra-domain B in oncofetal fibronectin structurally promotes fibrillar head-to-tail dimerization of extracellular matrix protein.

PubMed

Schiefner, André; Gebauer, Michaela; Skerra, Arne

2012-05-18

The type III extra-domain B (ED-B) is specifically spliced into fibronectin (Fn) during embryogenesis and neoangiogenesis, including many cancers. The x-ray structure of the recombinant four-domain fragment Fn(III)7B89 reveals a tightly associated, extended head-to-tail dimer, which is stabilized via pair-wise shape and charge complementarity. A tendency toward ED-B-dependent dimer formation in solution was supported by size exclusion chromatography and analytical ultracentrifugation. When amending the model with the known three-dimensional structure of the Fn(III)10 domain, its RGD loop as well as the adhesion synergy region in Fn(III)9-10 become displayed on the same face of the dimer; this should allow simultaneous binding of at least two integrins and, thus, receptor clustering on the cell surface and intracellular signaling. Insertion of ED-B appears to stabilize overall head-to-tail dimerization of two separate Fn chains, which, together with alternating homodimer formation via disulfide bridges at the C-terminal Fn tail, should lead to the known macromolecular fibril formation.

Inside-out Ca2+ signalling prompted by STIM1 conformational switch

NASA Astrophysics Data System (ADS)

Ma, Guolin; Wei, Ming; He, Lian; Liu, Chongxu; Wu, Bo; Zhang, Shenyuan L.; Jing, Ji; Liang, Xiaowen; Senes, Alessandro; Tan, Peng; Li, Siwei; Sun, Aomin; Bi, Yunchen; Zhong, Ling; Si, Hongjiang; Shen, Yuequan; Li, Minyong; Lee, Mi-Sun; Zhou, Weibin; Wang, Junfeng; Wang, Youjun; Zhou, Yubin

2015-07-01

Store-operated Ca2+ entry mediated by STIM1 and ORAI1 constitutes one of the major Ca2+ entry routes in mammalian cells. The molecular choreography of STIM1-ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca2+ store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca2+ signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels.

Spatially resolved mapping of electrical conductivity across individual domain (grain) boundaries in graphene.

PubMed

Clark, Kendal W; Zhang, X-G; Vlassiouk, Ivan V; He, Guowei; Feenstra, Randall M; Li, An-Ping

2013-09-24

All large-scale graphene films contain extended topological defects dividing graphene into domains or grains. Here, we spatially map electronic transport near specific domain and grain boundaries in both epitaxial graphene grown on SiC and CVD graphene on Cu subsequently transferred to a SiO2 substrate, with one-to-one correspondence to boundary structures. Boundaries coinciding with the substrate step on SiC exhibit a significant potential barrier for electron transport of epitaxial graphene due to the reduced charge transfer from the substrate near the step edge. Moreover, monolayer-bilayer boundaries exhibit a high resistance that can change depending on the height of substrate step coinciding at the boundary. In CVD graphene, the resistance of a grain boundary changes with the width of the disordered transition region between adjacent grains. A quantitative modeling of boundary resistance reveals the increased electron Fermi wave vector within the boundary region, possibly due to boundary induced charge density variation. Understanding how resistance change with domain (grain) boundary structure in graphene is a crucial first step for controlled engineering of defects in large-scale graphene films.

Modeling the Sedimentation of Red Blood Cells in Flow under Strong External Magnetic Body Force using a Lattice Boltzmann Fictitious Domain Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xing; Lin, Guang

To model the sedimentation of the red blood cell (RBC) in a square duct and a circular pipe, the recently developed technique derived from the lattice Boltzmann method and the distributed Lagrange multiplier/fictitious domain method (LBM-DLM/FD) is extended to employ the mesoscopic network model for simulations of the sedimentation of the RBC in flow. The flow is simulated by the lattice Boltzmann method with a strong magnetic body force, while the network model is used for modeling RBC deformation. The fluid-RBC interactions are enforced by the Lagrange multiplier. The sedimentation of the RBC in a square duct and a circularmore » pipe is simulated, revealing the capacity of the current method for modeling the sedimentation of RBC in various flows. Numerical results illustrate that that the terminal setting velocity increases with the increment of the exerted body force. The deformation of the RBC has significant effect on the terminal setting velocity due to the change of the frontal area. The larger the exerted force is, the smaller the frontal area and the larger deformation of the RBC are.« less

Finite-difference time-domain modelling of through-the-Earth radio signal propagation

NASA Astrophysics Data System (ADS)

Ralchenko, M.; Svilans, M.; Samson, C.; Roper, M.

2015-12-01

This research seeks to extend the knowledge of how a very low frequency (VLF) through-the-Earth (TTE) radio signal behaves as it propagates underground, by calculating and visualizing the strength of the electric and magnetic fields for an arbitrary geology through numeric modelling. To achieve this objective, a new software tool has been developed using the finite-difference time-domain method. This technique is particularly well suited to visualizing the distribution of electromagnetic fields in an arbitrary geology. The frequency range of TTE radio (400-9000 Hz) and geometrical scales involved (1 m resolution for domains a few hundred metres in size) involves processing a grid composed of millions of cells for thousands of time steps, which is computationally expensive. Graphics processing unit acceleration was used to reduce execution time from days and weeks, to minutes and hours. Results from the new modelling tool were compared to three cases for which an analytic solution is known. Two more case studies were done featuring complex geologic environments relevant to TTE communications that cannot be solved analytically. There was good agreement between numeric and analytic results. Deviations were likely caused by numeric artifacts from the model boundaries; however, in a TTE application in field conditions, the uncertainty in the conductivity of the various geologic formations will greatly outweigh these small numeric errors.

Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

PubMed

Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

2015-01-02

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.

PubMed

Favard, Cyril; Wenger, Jérôme; Lenne, Pierre-François; Rigneault, Hervé

2011-03-02

Many efforts have been undertaken over the last few decades to characterize the diffusion process in model and cellular lipid membranes. One of the techniques developed for this purpose, fluorescence correlation spectroscopy (FCS), has proved to be a very efficient approach, especially if the analysis is extended to measurements on different spatial scales (referred to as FCS diffusion laws). In this work, we examine the relevance of FCS diffusion laws for probing the behavior of a pure lipid and a lipid mixture at temperatures below, within and above the phase transitions, both experimentally and numerically. The accuracy of the microscopic description of the lipid mixtures found here extends previous work to a more complex model in which the geometry is unknown and the molecular motion is driven only by the thermodynamic parameters of the system itself. For multilamellar vesicles of both pure lipid and lipid mixtures, the FCS diffusion laws recorded at different temperatures exhibit large deviations from pure Brownian motion and reveal the existence of nanodomains. The variation of the mean size of these domains with temperature is in perfect correlation with the enthalpy fluctuation. This study highlights the advantages of using FCS diffusion laws in complex lipid systems to describe their temporal and spatial structure. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The hourly updated US High-Resolution Rapid Refresh (HRRR) storm-scale forecast model

NASA Astrophysics Data System (ADS)

Alexander, Curtis; Dowell, David; Benjamin, Stan; Weygandt, Stephen; Olson, Joseph; Kenyon, Jaymes; Grell, Georg; Smirnova, Tanya; Ladwig, Terra; Brown, John; James, Eric; Hu, Ming

2016-04-01

The 3-km convective-allowing High-Resolution Rapid Refresh (HRRR) is a US NOAA hourly updating weather forecast model that use a specially configured version of the Advanced Research WRF (ARW) model and assimilate many novel and most conventional observation types on an hourly basis using Gridpoint Statistical Interpolation (GSI). Included in this assimilation is a procedure for initializing ongoing precipitation systems from observed radar reflectivity data (and proxy reflectivity from lightning and satellite data), a cloud analysis to initialize stable layer clouds from METAR and satellite observations, and special techniques to enhance retention of surface observation information. The HRRR is run hourly out to 15 forecast hours over a domain covering the entire conterminous United States using initial and boundary conditions from the hourly-cycled 13km Rapid Refresh (RAP, using similar physics and data assimilation) covering North America and a significant part of the Northern Hemisphere. The HRRR is continually developed and refined at NOAA's Earth System Research Laboratory, and an initial version was implemented into the operational NOAA/NCEP production suite in September 2014. Ongoing experimental RAP and HRRR model development throughout 2014 and 2015 has culminated in a set of data assimilation and model enhancements that will be incorporated into the first simultaneous upgrade of both the operational RAP and HRRR that is scheduled for spring 2016 at NCEP. This presentation will discuss the operational RAP and HRRR changes contained in this upgrade. The RAP domain is being expanded to encompass the NAM domain and the forecast lengths of both the RAP and HRRR are being extended. RAP and HRRR assimilation enhancements have focused on (1) extending surface data assimilation to include mesonet observations and improved use of all surface observations through better background estimates of 2-m temperature and dewpoint including projection of 2-m temperature observations through the model boundary layer and (2) extending the use of radar observations to include both radial velocity and 3-D retrieval of rain hydrometeors from observed radar reflectivities in the warm-season. The RAP hybrid EnKF 3D-variational data assimilation will increase weighting of GFS ensemble-based background error covariance estimation and introduce this hybrid data assimilation configuration in the HRRR. Enhancement of RAP and HRRR model physics include improved land surface and boundary layer prediction using the updated Mellor-Yamada-Nakanishi-Niino (MYNN) parameterization scheme, Grell-Freitas-Olson (GFO) shallow and deep convective parameterization, aerosol-aware Thompson microphysics and upgraded Rapid Update Cycle (RUC) land-surface model. The presentation will highlight improvements in the RAP and HRRR model physics to reduce certain systematic forecast biases including a warm and dry daytime bias over the central and eastern CONUS during the warm season along with improved convective forecasts in more weakly-forced diurnally-driven events. Examples of RAP and HRRR forecast improvements will be demonstrated through both retrospective and real-time verification statistics and case-study examples.

Mapping the Martian Meteorology

NASA Technical Reports Server (NTRS)

Allison, Michael; Ross, J. D.; Soloman, N.

1999-01-01

The Mars-adapted version of the NASA/GISS general circulation model (GCM) has been applied to the hourly/daily simulation of the planet's meteorology over several seasonal orbits. The current running version of the model includes a diurnal solar cycle, CO2 sublimation, and a mature parameterization of upper level wave drag with a vertical domain extending from the surface up to the 6 micro b level. The benchmark simulations provide a four-dimensional archive for the comparative evaluation of various schemes for the retrieval of winds from anticipated polar orbiter measurements of temperatures by the Pressure Modulator Infrared Radiometer.

Alteration of the C-terminal ligand specificity of the erbin PDZ domain by allosteric mutational effects.

PubMed

Murciano-Calles, Javier; McLaughlin, Megan E; Erijman, Ariel; Hooda, Yogesh; Chakravorty, Nishant; Martinez, Jose C; Shifman, Julia M; Sidhu, Sachdev S

2014-10-23

Modulation of protein binding specificity is important for basic biology and for applied science. Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus. Our goal was to engineer variants of the Erbin PDZ domain with altered specificity for the most C-terminal position (position 0) where a Val is strongly preferred by the wild-type domain. We constructed a library of PDZ domains by randomizing residues in direct contact with position 0 and in a loop that is close to but does not contact position 0. We used phage display to select for PDZ variants that bind to 19 peptide ligands differing only at position 0. To verify that each obtained PDZ domain exhibited the correct binding specificity, we selected peptide ligands for each domain. Despite intensive efforts, we were only able to evolve Erbin PDZ domain variants with selectivity for the aliphatic C-terminal side chains Val, Ile and Leu. Interestingly, many PDZ domains with these three distinct specificities contained identical amino acids at positions that directly contact position 0 but differed in the loop that does not contact position 0. Computational modeling of the selected PDZ domains shows how slight conformational changes in the loop region propagate to the binding site and result in different binding specificities. Our results demonstrate that second-sphere residues could be crucial in determining protein binding specificity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Search algorithm complexity modeling with application to image alignment and matching

NASA Astrophysics Data System (ADS)

DelMarco, Stephen

2014-05-01

Search algorithm complexity modeling, in the form of penetration rate estimation, provides a useful way to estimate search efficiency in application domains which involve searching over a hypothesis space of reference templates or models, as in model-based object recognition, automatic target recognition, and biometric recognition. The penetration rate quantifies the expected portion of the database that must be searched, and is useful for estimating search algorithm computational requirements. In this paper we perform mathematical modeling to derive general equations for penetration rate estimates that are applicable to a wide range of recognition problems. We extend previous penetration rate analyses to use more general probabilistic modeling assumptions. In particular we provide penetration rate equations within the framework of a model-based image alignment application domain in which a prioritized hierarchical grid search is used to rank subspace bins based on matching probability. We derive general equations, and provide special cases based on simplifying assumptions. We show how previously-derived penetration rate equations are special cases of the general formulation. We apply the analysis to model-based logo image alignment in which a hierarchical grid search is used over a geometric misalignment transform hypothesis space. We present numerical results validating the modeling assumptions and derived formulation.

Multiscale Multiphysics and Multidomain Models I: Basic Theory

PubMed Central

Wei, Guo-Wei

2013-01-01

This work extends our earlier two-domain formulation of a differential geometry based multiscale paradigm into a multidomain theory, which endows us the ability to simultaneously accommodate multiphysical descriptions of aqueous chemical, physical and biological systems, such as fuel cells, solar cells, nanofluidics, ion channels, viruses, RNA polymerases, molecular motors and large macromolecular complexes. The essential idea is to make use of the differential geometry theory of surfaces as a natural means to geometrically separate the macroscopic domain of solvent from the microscopic domain of solute, and dynamically couple continuum and discrete descriptions. Our main strategy is to construct energy functionals to put on an equal footing of multiphysics, including polar (i.e., electrostatic) solvation, nonpolar solvation, chemical potential, quantum mechanics, fluid mechanics, molecular mechanics, coarse grained dynamics and elastic dynamics. The variational principle is applied to the energy functionals to derive desirable governing equations, such as multidomain Laplace-Beltrami (LB) equations for macromolecular morphologies, multidomain Poisson-Boltzmann (PB) equation or Poisson equation for electrostatic potential, generalized Nernst-Planck (NP) equations for the dynamics of charged solvent species, generalized Navier-Stokes (NS) equation for fluid dynamics, generalized Newton's equations for molecular dynamics (MD) or coarse-grained dynamics and equation of motion for elastic dynamics. Unlike the classical PB equation, our PB equation is an integral-differential equation due to solvent-solute interactions. To illustrate the proposed formalism, we have explicitly constructed three models, a multidomain solvation model, a multidomain charge transport model and a multidomain chemo-electro-fluid-MD-elastic model. Each solute domain is equipped with distinct surface tension, pressure, dielectric function, and charge density distribution. In addition to long-range Coulombic interactions, various non-electrostatic solvent-solute interactions are considered in the present modeling. We demonstrate the consistency between the non-equilibrium charge transport model and the equilibrium solvation model by showing the systematical reduction of the former to the latter at equilibrium. This paper also offers a brief review of the field. PMID:25382892

Multiscale Multiphysics and Multidomain Models I: Basic Theory.

PubMed

Wei, Guo-Wei

2013-12-01

This work extends our earlier two-domain formulation of a differential geometry based multiscale paradigm into a multidomain theory, which endows us the ability to simultaneously accommodate multiphysical descriptions of aqueous chemical, physical and biological systems, such as fuel cells, solar cells, nanofluidics, ion channels, viruses, RNA polymerases, molecular motors and large macromolecular complexes. The essential idea is to make use of the differential geometry theory of surfaces as a natural means to geometrically separate the macroscopic domain of solvent from the microscopic domain of solute, and dynamically couple continuum and discrete descriptions. Our main strategy is to construct energy functionals to put on an equal footing of multiphysics, including polar (i.e., electrostatic) solvation, nonpolar solvation, chemical potential, quantum mechanics, fluid mechanics, molecular mechanics, coarse grained dynamics and elastic dynamics. The variational principle is applied to the energy functionals to derive desirable governing equations, such as multidomain Laplace-Beltrami (LB) equations for macromolecular morphologies, multidomain Poisson-Boltzmann (PB) equation or Poisson equation for electrostatic potential, generalized Nernst-Planck (NP) equations for the dynamics of charged solvent species, generalized Navier-Stokes (NS) equation for fluid dynamics, generalized Newton's equations for molecular dynamics (MD) or coarse-grained dynamics and equation of motion for elastic dynamics. Unlike the classical PB equation, our PB equation is an integral-differential equation due to solvent-solute interactions. To illustrate the proposed formalism, we have explicitly constructed three models, a multidomain solvation model, a multidomain charge transport model and a multidomain chemo-electro-fluid-MD-elastic model. Each solute domain is equipped with distinct surface tension, pressure, dielectric function, and charge density distribution. In addition to long-range Coulombic interactions, various non-electrostatic solvent-solute interactions are considered in the present modeling. We demonstrate the consistency between the non-equilibrium charge transport model and the equilibrium solvation model by showing the systematical reduction of the former to the latter at equilibrium. This paper also offers a brief review of the field.

The TLR4 agonist fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer vaccine

DOE PAGES

Julier, Ziad; Martino, Mikaël M.; de Titta, Alexandre; ...

2015-02-24

Fibronectin (FN) is an extracellular matrix (ECM) protein including numerous fibronectin type III (FNIII) repeats with different functions. The alternatively spliced FN variant containing the extra domain A (FNIII EDA), located between FNIII 11 and FNIII 12, is expressed in sites of injury, chronic inflammation, and solid tumors. Although its function is not well understood, FNIII EDA is known to agonize Toll-like receptor 4 (TLR4). Here, by producing various FN fragments containing FNIII EDA, we found that FNIII EDA's immunological activity depends upon its local intramolecular context within the FN chain. N-terminal extension of the isolated FNIII EDA with itsmore » neighboring FNIII repeats (FNIII 9-10-11) enhanced its activity in agonizing TLR4, while C-terminal extension with the native FNIII 12-13-14 heparin-binding domain abrogated it. We reveal that an elastase 2 cleavage site is present between FNIII EDA and FNIII 12. Activity of the C-terminally extended FNIII EDA could be restored after cleavage of the FNIII 12-13-14 domain by elastase 2. FN being naturally bound to the ECM, we immobilized FNIII EDA-containing FN fragments within a fibrin matrix model along with antigenic peptides. Such matrices were shown to stimulate cytotoxic CD8 + T cell responses in two murine cancer models.« less

Effects of biases in domain wall network evolution. II. Quantitative analysis

NASA Astrophysics Data System (ADS)

Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

2018-04-01

Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

A steady-state model of spreading depression predicts the importance of an unknown conductance in specific dendritic domains.

PubMed

Makarova, Julia; Ibarz, José M; Canals, Santiago; Herreras, Oscar

2007-06-15

Spreading depression (SD) is a pathological wave of transient neuronal inactivation. We recently reported that the characteristic sustained complete depolarization is restricted to specific cell domains where the input resistance (R(in)) first becomes negligible before achieving partial recovery, whereas in adjacent, more polarized membranes it drops by much less. The experimental study of the participating membrane channels is hindered by their mixed contribution and heterogeneous distribution. Therefore, we derived a biophysical model to analyze the conductances that replicate the subcellular profile of R(in) during SD. Systematic variation of conductance densities far beyond the ranges reported failed to fit the experimental values. Besides standard potassium, sodium, and Glu-mediated conductances, the initial opening and gradual closing of an as yet undetermined large conductance is required to account for the evolution of R(in). Potassium conductances follow in the relative contribution and their closing during the late phase is also predicted. Large intracellular potential gradients from zero to rest are readily sustained between shunted and adjacent SD-spared membranes, which remain electroregenerative. The gradients are achieved by a combination of high-conductance subcellular domains and transmembrane ion redistribution in extended but discrete dendritic domains. We conclude that the heterogeneous subcellular behavior is due to local membrane properties, some of which may be specifically activated under extreme SD conditions.

The organization of domains in proteins obeys Menzerath-Altmann's law of language.

PubMed

Shahzad, Khuram; Mittenthal, Jay E; Caetano-Anollés, Gustavo

2015-08-11

The combination of domains in multidomain proteins enhances their function and structure but lengthens the molecules and increases their cost at cellular level. The dependence of domain length on the number of domains a protein holds was surveyed for a set of 60 proteomes representing free-living organisms from all kingdoms of life. Distributions were fitted using non-linear functions and fitted parameters interpreted with a formulation of decreasing returns. We find that domain length decreases with increasing number of domains in proteins, following the Menzerath-Altmann (MA) law of language. Highly significant negative correlations exist for the set of proteomes examined. Mathematically, the MA law expresses as a power law relationship that unfolds when molecular persistence P is a function of domain accretion. P holds two terms, one reflecting the matter-energy cost of adding domains and extending their length, the other reflecting how domain length and number impinges on information and biophysics. The pattern of diminishing returns can therefore be explained as a frustrated interplay between the strategies of economy, flexibility and robustness, matching previously observed trade-offs in the domain makeup of proteomes. Proteomes of Archaea, Fungi and to a lesser degree Plants show the largest push towards molecular economy, each at their own economic stratum. Fungi increase domain size in single domain proteins while reinforcing the pattern of diminishing returns. In contrast, Metazoa, and to lesser degrees Protista and Bacteria, relax economy. Metazoa achieves maximum flexibility and robustness by harboring compact molecules and complex domain organization, offering a new functional vocabulary for molecular biology. The tendency of parts to decrease their size when systems enlarge is universal for language and music, and now for parts of macromolecules, extending the MA law to natural systems.

Reconstructing cortical current density by exploring sparseness in the transform domain

NASA Astrophysics Data System (ADS)

Ding, Lei

2009-05-01

In the present study, we have developed a novel electromagnetic source imaging approach to reconstruct extended cortical sources by means of cortical current density (CCD) modeling and a novel EEG imaging algorithm which explores sparseness in cortical source representations through the use of L1-norm in objective functions. The new sparse cortical current density (SCCD) imaging algorithm is unique since it reconstructs cortical sources by attaining sparseness in a transform domain (the variation map of cortical source distributions). While large variations are expected to occur along boundaries (sparseness) between active and inactive cortical regions, cortical sources can be reconstructed and their spatial extents can be estimated by locating these boundaries. We studied the SCCD algorithm using numerous simulations to investigate its capability in reconstructing cortical sources with different extents and in reconstructing multiple cortical sources with different extent contrasts. The SCCD algorithm was compared with two L2-norm solutions, i.e. weighted minimum norm estimate (wMNE) and cortical LORETA. Our simulation data from the comparison study show that the proposed sparse source imaging algorithm is able to accurately and efficiently recover extended cortical sources and is promising to provide high-accuracy estimation of cortical source extents.

Using object-oriented analysis techniques to support system testing

NASA Astrophysics Data System (ADS)

Zucconi, Lin

1990-03-01

Testing of real-time control systems can be greatly facilitated by use of object-oriented and structured analysis modeling techniques. This report describes a project where behavior, process and information models built for a real-time control system were used to augment and aid traditional system testing. The modeling techniques used were an adaptation of the Ward/Mellor method for real-time systems analysis and design (Ward85) for object-oriented development. The models were used to simulate system behavior by means of hand execution of the behavior or state model and the associated process (data and control flow) and information (data) models. The information model, which uses an extended entity-relationship modeling technique, is used to identify application domain objects and their attributes (instance variables). The behavioral model uses state-transition diagrams to describe the state-dependent behavior of the object. The process model uses a transformation schema to describe the operations performed on or by the object. Together, these models provide a means of analyzing and specifying a system in terms of the static and dynamic properties of the objects which it manipulates. The various models were used to simultaneously capture knowledge about both the objects in the application domain and the system implementation. Models were constructed, verified against the software as-built and validated through informal reviews with the developer. These models were then hand-executed.

Zero-moment point determination of worst-case manoeuvres leading to vehicle wheel lift

NASA Astrophysics Data System (ADS)

Lapapong, S.; Brown, A. A.; Swanson, K. S.; Brennan, S. N.

2012-01-01

This paper proposes a method to evaluate vehicle rollover propensity based on a frequency-domain representation of the zero-moment point (ZMP). Unlike other rollover metrics such as the static stability factor, which is based on the steady-state behaviour, and the load transfer ratio, which requires the calculation of tyre forces, the ZMP is based on a simplified kinematic model of the vehicle and the analysis of the contact point of the vehicle relative to the edge of the support polygon. Previous work has validated the use of the ZMP experimentally in its ability to predict wheel lift in the time domain. This work explores the use of the ZMP in the frequency domain to allow a chassis designer to understand how operating conditions and vehicle parameters affect rollover propensity. The ZMP analysis is then extended to calculate worst-case sinusoidal manoeuvres that lead to untripped wheel lift, and the analysis is tested across several vehicle configurations and compared with that of the standard Toyota J manoeuvre.

LayTracks3D: A new approach for meshing general solids using medial axis transform

DOE PAGES

Quadros, William Roshan

2015-08-22

This study presents an extension of the all-quad meshing algorithm called LayTracks to generate high quality hex-dominant meshes of general solids. LayTracks3D uses the mapping between the Medial Axis (MA) and the boundary of the 3D domain to decompose complex 3D domains into simpler domains called Tracks. Tracks in 3D have no branches and are symmetric, non-intersecting, orthogonal to the boundary, and the shortest path from the MA to the boundary. These properties of tracks result in desired meshes with near cube shape elements at the boundary, structured mesh along the boundary normal with any irregular nodes restricted to themore » MA, and sharp boundary feature preservation. The algorithm has been tested on a few industrial CAD models and hex-dominant meshes are shown in the Results section. Work is underway to extend LayTracks3D to generate all-hex meshes.« less

Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo

PubMed Central

Stadler, Michael R; Haines, Jenna E

2017-01-01

High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters. Further, we show a striking correspondence between these elements and the locations of mapped polytene interband regions. We believe it is likely this relationship between insulators, topological boundaries, and polytene interbands extends across the genome, and we therefore propose a model in which decompaction of boundary-insulator-interband regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains. PMID:29148971

Properties of branching exponential flights in bounded domains

NASA Astrophysics Data System (ADS)

Zoia, A.; Dumonteil, E.; Mazzolo, A.

2012-11-01

In a series of recent works, important results have been reported concerning the statistical properties of exponential flights evolving in bounded domains, a widely adopted model for finite-speed transport phenomena (Blanco S. and Fournier R., Europhys. Lett., 61 (2003) 168; Mazzolo A., Europhys. Lett., 68 (2004) 350; Bénichou O. et al., Europhys. Lett., 70 (2005) 42). Motivated by physical and biological systems where random spatial displacements are coupled with Galton-Watson birth-death mechanisms, such as neutron multiplication, diffusion of reproducing bacteria or spread of epidemics, in this letter we extend those results in two directions, via a Feynman-Kac formalism. First, we characterize the occupation statistics of exponential flights in the presence of absorption and branching, and give explicit moment formulas for the total length travelled by the walker and the number of performed collisions in a given domain. Then, we show that the survival and escape probability can be derived as well by resorting to a similar approach.

Dynamics of SARS-coronavirus HR2 domain in the prefusion and transition states

NASA Astrophysics Data System (ADS)

McReynolds, Susanna; Jiang, Shaokai; Rong, Lijun; Caffrey, Michael

2009-12-01

The envelope glycoproteins S1 and S2 of severe acute respiratory syndrome coronavirus (SARS-CoV) mediate viral entry by conformational change from a prefusion state to a postfusion state that enables fusion of the viral and target membranes. In this work we present the characterization of the dynamic properties of the SARS-CoV S2-HR2 domain (residues 1141-1193 of S) in the prefusion and newly discovered transition states by NMR 15N relaxation studies. The dynamic properties of the different states, which are stabilized under different experimental conditions, extend the current model of viral membrane fusion and give insight into the design of structure-based antagonists of SARS-CoV in particular, as well as other enveloped viruses such as HIV.

Filamentation instability in a quantum plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bret, A.

2007-08-15

The growth rate of the filamentation instability triggered when a diluted cold electron beam passes through a cold plasma is evaluated using the quantum hydrodynamic equations. Compared with a cold fluid model, quantum effects reduce both the unstable wave vector domain and the maximum growth rate. Stabilization of large wave vector modes is always achieved, but significant reduction of the maximum growth rate depends on a dimensionless parameter that is provided. Although calculations are extended to the relativistic regime, they are mostly relevant to the nonrelativistic one.

Application of a Water Quality Model to Mississippi Sound to Evaluate Impacts of Freshwater Diversions

DTIC Science & Technology

2007-09-01

Bunch et al. (2005) focused on the Port of Gulfport, the domain extended from east of Mobile Bay (including Mobile Bay), south to the Chandeleur ...more fully meet the needs of the MSCIP. The extension was southward beyond Chandeleur Islands and further west to include all of Lake Borgne and Lake...except for possibly chlorophyll a. This diversion elevates chloro- phyll a near the Chandeleur Islands, more so than the Bonnet Carre′ diver- sion

High Performance Computing Technologies for Modeling the Dynamics and Dispersion of Ice Chunks in the Arctic Ocean

DTIC Science & Technology

2016-08-23

SECURITY CLASSIFICATION OF: Hybrid finite element / finite volume based CaMEL shallow water flow solvers have been successfully extended to study wave...effects on ice floes in a simplified 10 sq-km ocean domain. Our solver combines the merits of both the finite element and finite volume methods and...ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 sea ice dynamics, shallow water, finite element , finite volume

The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

PubMed Central

Bourhis, Jean-Marie; Receveur-Bréchot, Véronique; Oglesbee, Michael; Zhang, Xinsheng; Buccellato, Matthew; Darbon, Hervé; Canard, Bruno; Finet, Stéphanie; Longhi, Sonia

2005-01-01

Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. PMID:16046624

Compositional layering within the large low shear-wave velocity provinces in the lower mantle

NASA Astrophysics Data System (ADS)

Ballmer, Maxim D.; Schumacher, Lina; Lekic, Vedran; Thomas, Christine; Ito, Garrett

2016-12-01

The large low shear-wave velocity provinces (LLSVP) are thermochemical anomalies in the deep Earth's mantle, thousands of km wide and ˜1800 km high. This study explores the hypothesis that the LLSVPs are compositionally subdivided into two domains: a primordial bottom domain near the core-mantle boundary and a basaltic shallow domain that extends from 1100 to 2300 km depth. This hypothesis reconciles published observations in that it predicts that the two domains have different physical properties (bulk-sound versus shear-wave speed versus density anomalies), the transition in seismic velocities separating them is abrupt, and both domains remain seismically distinct from the ambient mantle. We here report underside reflections from the top of the LLSVP shallow domain, supporting a compositional origin. By exploring a suite of two-dimensional geodynamic models, we constrain the conditions under which well-separated "double-layered" piles with realistic geometry can persist for billions of years. Results show that long-term separation requires density differences of ˜100 kg/m3 between LLSVP materials, providing a constraint for origin and composition. The models further predict short-lived "secondary" plumelets to rise from LLSVP roofs and to entrain basaltic material that has evolved in the lower mantle. Long-lived, vigorous "primary" plumes instead rise from LLSVP margins and entrain a mix of materials, including small fractions of primordial material. These predictions are consistent with the locations of hot spots relative to LLSVPs, and address the geochemical and geochronological record of (oceanic) hot spot volcanism. The study of large-scale heterogeneity within LLSVPs has important implications for our understanding of the evolution and composition of the mantle.

Modelling and interpreting fish bioenergetics: a role for behaviour, life-history traits and survival trade-offs

PubMed Central

Jørgensen, C; Enberg, K; Mangel, M

2016-01-01

Bioenergetics is used as the mechanistic foundation of many models of fishes. As the context of a model gradually extends beyond pure bioenergetics to include behaviour, life-history traits and function and performance of the entire organism, so does the need for complementing bioenergetic measurements with trade-offs, particularly those dealing with survival. Such a broadening of focus revitalized and expanded the domain of behavioural ecology in the 1980s. This review makes the case that a similar change of perspective is required for physiology to contribute to the types of predictions society currently demands, e.g. regarding climate change and other anthropogenic stressors. PMID:26768979

Correlated Debye model for atomic motions in metal nanocrystals

NASA Astrophysics Data System (ADS)

Scardi, P.; Flor, A.

2018-05-01

The Correlated Debye model for the mean square relative displacement of atoms in near-neighbour coordination shells has been extended to include the effect of finite crystal size. This correctly explains the increase in Debye-Waller coefficient observed for metal nanocrystals. A good match with Molecular Dynamics simulations of Pd nanocrystals is obtained if, in addition to the phonon confinement effect of the finite domain size, proper consideration is also given to the static disorder component caused by the undercoordination of surface atoms. The new model, which addresses the analysis of the Pair Distribution Function and powder diffraction data collected at different temperatures, was preliminarily tested on recently published experimental data on nanocrystalline Pt powders.

XFEL OSCILLATOR SIMULATION INCLUDING ANGLE-DEPENDENT CRYSTAL REFLECTIVITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fawley, William; Lindberg, Ryan; Kim, K-J

The oscillator package within the GINGER FEL simulation code has now been extended to include angle-dependent reflectivity properties of Bragg crystals. Previously, the package was modified to include frequencydependent reflectivity in order to model x-ray FEL oscillators from start-up from shot noise through to saturation. We present a summary of the algorithms used for modeling the crystal reflectivity and radiation propagation outside the undulator, discussing various numerical issues relevant to the domain of high Fresnel number and efficient Hankel transforms. We give some sample XFEL-O simulation results obtained with the angle-dependent reflectivity model, with particular attention directed to the longitudinalmore » and transverse coherence of the radiation output.« less

The electronic patient record: a strategic planning framework.

PubMed

Gordon, D B; Marafioti, S; Carter, M; Kunov, H; Dolan, A

1995-01-01

Sunnybrook Health Science Center (Sunnybrook) is a multifacility academic teaching center. In May 1994, Sunnybrook struck an electronic patient record taskforce to develop a strategic plan for the implementation of a comprehensive, facility wide electronic patient record (EPR). The taskforce sought to create a conceptual framework which provides context and integrates decision-making related to the comprehensive electronic patient record. The EPR is very much broader in scope than the traditional paper-based record. It is not restricted to simply reporting individual patient data. By the Institute of Medicine's definition, the electronic patient record resides in a system specifically designed to support users through availability of complete and accurate data, practitioner reminders and alerts, clinical decision support systems, links to bodies of medical knowledge, and other aids [1]. It is a comprehensive resource for patient care. The taskforce proposed a three domain model for determining how the EPR affects Sunnybrook. The EPR enables Sunnybrook to have a high performance team structure (domain 1), to function as an integrated organization (domain 2), and to reach out and develop new relationships with external organizations to become an extended enterprise (domain 3) [2]. Domain 1: Sunnybrook's high performance teams or patient service units' (PSUs) are decentralized, autonomous operating units that provide care to patients grouped by 'like' diagnosis and resource needs. The EPR must provide functions and applications which promote patient focused care, such as cross functional charting and care maps, group scheduling, clinical email, and a range of enabling technologies for multiskilled workers. Domain 2: In the integrated organization domain, the EPR should facilitate closer linkages between the arrangement of PSUs into clinical teams and with other facilities within the center in order to provide a longitudinal record that covers a continuum of care. Domain 3: In the inter-enterprise domain, the EPR must allow for patient information to be exchanged with external providers including referring doctors, laboratories, and other hospitals via community health information networks (CHINs). Sunnybrook will prioritize the development of first domain functionality within the corporate constraints imposed by the integrated organization domain. Inter-enterprise computing will be less of a priority until Sunnybrook has developed a critical mass of the electronic patient record internally. The three domain description is a useful model for describing the relationship between the electronic patient record enabling technologies and the Sunnybrook organizational structures. The taskforce has used this model to determine EPR development guidelines and implementation priorities.

A Multiple Agent Model of Human Performance in Automated Air Traffic Control and Flight Management Operations

NASA Technical Reports Server (NTRS)

Corker, Kevin; Pisanich, Gregory; Condon, Gregory W. (Technical Monitor)

1995-01-01

A predictive model of human operator performance (flight crew and air traffic control (ATC)) has been developed and applied in order to evaluate the impact of automation developments in flight management and air traffic control. The model is used to predict the performance of a two person flight crew and the ATC operators generating and responding to clearances aided by the Center TRACON Automation System (CTAS). The purpose of the modeling is to support evaluation and design of automated aids for flight management and airspace management and to predict required changes in procedure both air and ground in response to advancing automation in both domains. Additional information is contained in the original extended abstract.

Development of a Risk-Based Comparison Methodology of Carbon Capture Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engel, David W.; Dalton, Angela C.; Dale, Crystal

2014-06-01

Given the varying degrees of maturity among existing carbon capture (CC) technology alternatives, an understanding of the inherent technical and financial risk and uncertainty associated with these competing technologies is requisite to the success of carbon capture as a viable solution to the greenhouse gas emission challenge. The availability of tools and capabilities to conduct rigorous, risk–based technology comparisons is thus highly desirable for directing valuable resources toward the technology option(s) with a high return on investment, superior carbon capture performance, and minimum risk. To address this research need, we introduce a novel risk-based technology comparison method supported by anmore » integrated multi-domain risk model set to estimate risks related to technological maturity, technical performance, and profitability. Through a comparison between solid sorbent and liquid solvent systems, we illustrate the feasibility of estimating risk and quantifying uncertainty in a single domain (modular analytical capability) as well as across multiple risk dimensions (coupled analytical capability) for comparison. This method brings technological maturity and performance to bear on profitability projections, and carries risk and uncertainty modeling across domains via inter-model sharing of parameters, distributions, and input/output. The integration of the models facilitates multidimensional technology comparisons within a common probabilistic risk analysis framework. This approach and model set can equip potential technology adopters with the necessary computational capabilities to make risk-informed decisions about CC technology investment. The method and modeling effort can also be extended to other industries where robust tools and analytical capabilities are currently lacking for evaluating nascent technologies.« less

Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

NASA Astrophysics Data System (ADS)

Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

2018-04-01

Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.

Size effects of 109° domain walls in rhombohedral barium titanate single crystals—A molecular statics analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Endres, Florian, E-mail: florian.endres@ltm.uni-erlangen.de; Steinmann, Paul, E-mail: paul.steinmann@ltm.uni-erlangen.de

2016-01-14

Ferroelectric functional materials are of great interest in science and technology due to their electromechanically coupled material properties. Therefore, ferroelectrics, such as barium titanate, are modeled and simulated at the continuum scale as well as at the atomistic scale. Due to recent advancements in related manufacturing technologies the modeling and simulation of smart materials at the nanometer length scale is getting more important not only to predict but also fundamentally understand the complex material behavior of such materials. In this study, we analyze the size effects of 109° nanodomain walls in ferroelectric barium titanate single crystals in the rhombohedral phasemore » using a recently proposed extended molecular statics algorithm. We study the impact of domain thicknesses on the spontaneous polarization, the coercive field, and the lattice constants. Moreover, we discuss how the electromechanical coupling of an applied electric field and the introduced strain in the converse piezoelectric effect is affected by the thickness of nanodomains.« less

A cosmic superfluid phase

NASA Technical Reports Server (NTRS)

Gradwohl, Ben-Ami

1991-01-01

The universe may have undergone a superfluid-like phase during its evolution, resulting from the injection of nontopological charge into the spontaneously broken vacuum. In the presence of vortices this charge is identified with angular momentum. This leads to turbulent domains on the scale of the correlation length. By restoring the symmetry at low temperatures, the vortices dissociate and push the charges to the boundaries of these domains. The model can be scaled (phenomenologically) to very low energies, it can be incorporated in a late time phase transition and form large scale structure in the boundary layers of the correlation volumes. The novel feature of the model lies in the fact that the dark matter is endowed with coherent motion. The possibilities of identifying this flow around superfluid vortices with the observed large scale bulk motion is discussed. If this identification is possible, then the definite prediction can be made that a more extended map of peculiar velocities would have to reveal large scale circulations in the flow pattern.

Domain structure of human complement C4b extends with increasing NaCl concentration: implications for its regulatory mechanism.

PubMed

Fung, Ka Wai; Wright, David W; Gor, Jayesh; Swann, Marcus J; Perkins, Stephen J

2016-12-01

During the activation of complement C4 to C4b, the exposure of its thioester domain (TED) is crucial for the attachment of C4b to activator surfaces. In the C4b crystal structure, TED forms an Arg 104 -Glu 1032 salt bridge to tether its neighbouring macroglobulin (MG1) domain. Here, we examined the C4b domain structure to test whether this salt bridge affects its conformation. Dual polarisation interferometry of C4b immobilised at a sensor surface showed that the maximum thickness of C4b increased by 0.46 nm with an increase in NaCl concentration from 50 to 175 mM NaCl. Analytical ultracentrifugation showed that the sedimentation coefficient s 20,w of monomeric C4b of 8.41 S in 50 mM NaCl buffer decreased to 7.98 S in 137 mM NaCl buffer, indicating that C4b became more extended. Small angle X-ray scattering reported similar R G values of 4.89-4.90 nm for C4b in 137-250 mM NaCl. Atomistic scattering modelling of the C4b conformation showed that TED and the MG1 domain were separated by 4.7 nm in 137-250 mM NaCl and this is greater than that of 4.0 nm in the C4b crystal structure. Our data reveal that in low NaCl concentrations, both at surfaces and in solution, C4b forms compact TED-MG1 structures. In solution, physiologically relevant NaCl concentrations lead to the separation of the TED and MG1 domain, making C4b less capable of binding to its complement regulators. These conformational changes are similar to those seen previously for complement C3b, confirming the importance of this salt bridge for regulating both C4b and C3b. © 2016 The Author(s).

Vertically-Integrated Dual-Continuum Models for CO2 Injection in Fractured Aquifers

NASA Astrophysics Data System (ADS)

Tao, Y.; Guo, B.; Bandilla, K.; Celia, M. A.

2017-12-01

Injection of CO2 into a saline aquifer leads to a two-phase flow system, with supercritical CO2 and brine being the two fluid phases. Various modeling approaches, including fully three-dimensional (3D) models and vertical-equilibrium (VE) models, have been used to study the system. Almost all of that work has focused on unfractured formations. 3D models solve the governing equations in three dimensions and are applicable to generic geological formations. VE models assume rapid and complete buoyant segregation of the two fluid phases, resulting in vertical pressure equilibrium and allowing integration of the governing equations in the vertical dimension. This reduction in dimensionality makes VE models computationally more efficient, but the associated assumptions restrict the applicability of VE model to formations with moderate to high permeability. In this presentation, we extend the VE and 3D models for CO2 injection in fractured aquifers. This is done in the context of dual-continuum modeling, where the fractured formation is modeled as an overlap of two continuous domains, one representing the fractures and the other representing the rock matrix. Both domains are treated as porous media continua and can be modeled by either a VE or a 3D formulation. The transfer of fluid mass between rock matrix and fractures is represented by a mass transfer function connecting the two domains. We have developed a computational model that combines the VE and 3D models, where we use the VE model in the fractures, which typically have high permeability, and the 3D model in the less permeable rock matrix. A new mass transfer function is derived, which couples the VE and 3D models. The coupled VE-3D model can simulate CO2 injection and migration in fractured aquifers. Results from this model compare well with a full-3D model in which both the fractures and rock matrix are modeled with 3D models, with the hybrid VE-3D model having significantly reduced computational cost. In addition to the VE-3D model, we explore simplifications of the rock matrix domain by using sugar-cube and matchstick conceptualizations and develop VE-dual porosity and VE-matchstick models. These vertically-integrated dual-permeability and dual-porosity models provide a range of computationally efficient tools to model CO2 storage in fractured saline aquifers.

A model-driven approach to information security compliance

NASA Astrophysics Data System (ADS)

Correia, Anacleto; Gonçalves, António; Teodoro, M. Filomena

2017-06-01

The availability, integrity and confidentiality of information are fundamental to the long-term survival of any organization. Information security is a complex issue that must be holistically approached, combining assets that support corporate systems, in an extended network of business partners, vendors, customers and other stakeholders. This paper addresses the conception and implementation of information security systems, conform the ISO/IEC 27000 set of standards, using the model-driven approach. The process begins with the conception of a domain level model (computation independent model) based on information security vocabulary present in the ISO/IEC 27001 standard. Based on this model, after embedding in the model mandatory rules for attaining ISO/IEC 27001 conformance, a platform independent model is derived. Finally, a platform specific model serves the base for testing the compliance of information security systems with the ISO/IEC 27000 set of standards.

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

DOE PAGES

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.; ...

2018-02-06

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Preliminary development of a revised version of the School Climate Measure.

PubMed

Zullig, Keith J; Collins, Rani; Ghani, Nadia; Hunter, Amy A; Patton, Jon M; Huebner, E Scott; Zhang, Jianjun

2015-09-01

The School Climate Measure (SCM) was developed and preliminarily validated in 2010 and extended upon in 2013 in response to a dearth of psychometrically sound school climate instruments. This study sought to further validate the SCM on a large diverse sample of Arizona public school adolescents (N = 1,643) with two new domains. The eight original SCM domains (Positive Student-Teacher Relationships, School Connectedness, Academic Support, Order and Discipline, Physical Environment, Social Environment, Perceived Exclusion, and Academic Satisfaction) and two newly developed domains (Parental Involvement and Opportunities for Student Engagement) were subjected to psychometric analysis. The sample was randomly split into exploratory and confirmatory halves and subjected to factor analytic and structural equation modeling techniques. Factor analysis confirmed a 10-factor solution (loadings with absolute values > .40). Item factor loadings ranged from .47 to .95. Coefficient alphas ranged from .70 to .92. Fit statistics indicated a good fitting model (χ2 = 1452.67 [df = 734, p < .01], CFI = .94, TLI = .93, RMSEA = .039). This process eliminated some original SCM items, but the overall SCM increased only from 39 to 42 items with the newly developed domains. This investigation adds to the existing evidence for the SCM and offers support for a more comprehensive version of the SCM. The addition of the Parental Involvement and Opportunities for Student Engagement domains should further enhance the usefulness of the SCM. The SCM can facilitate data-driven decisions and may be incorporated into evidenced-based processes designed to improve important student learning and well-being outcomes. (c) 2015 APA, all rights reserved.

A new competency model for general practice: implications for selection, training, and careers.

PubMed

Patterson, Fiona; Tavabie, Abdol; Denney, MeiLing; Kerrin, Máire; Ashworth, Vicki; Koczwara, Anna; MacLeod, Sheona

2013-05-01

Recent structural and policy changes in the UK health service have significantly changed the job responsibilities for the GP role. To replicate a previous job analysis study to examine the relevance of current competency domains and selection criteria for doctors entering training. A multisource, multimethod approach comprising three phases: (1) stakeholder consultation (n = 205) using interviews, focus groups and behavioural observation of practising GPs; (2) a validation questionnaire based on results from phase 1 (n = 1082); followed by (3) an expert panel (n = 6) to review and confirm the final competency domains. Eleven competency domains were identified, which extends previous research findings. A new domain was identified called Leading for Continuing Improvement. Results show that, Empathy and Perspective Taking, Communication Skills, Clinical Knowledge and Expertise, and Professional Integrity are currently rated the most important domains. Results indicate a significant increase in ratings of importance for each domain in the future (P<0.001), except for Communication Skills and Empathy and Perspective Taking, which consistently remain high. The breadth of competencies required for GPs has increased significantly. GPs are now required to resolve competing tensions to be effective in their role, such as maintaining a patient focus while overseeing commissioning, with a potential ethical conflict between these aspects. Selection criteria remain largely unchanged but with increased priority in some domains (for example, Effective Teamworking). However, there is an urgent need to review the training provision arrangements to reflect the greater breadth of competencies now required.

Pair correlation functions for identifying spatial correlation in discrete domains

NASA Astrophysics Data System (ADS)

Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

2018-06-01

Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

Crosslinking-MS analysis reveals RNA polymerase I domain architecture and basis of rRNA cleavage

PubMed Central

Jennebach, Stefan; Herzog, Franz; Aebersold, Ruedi; Cramer, Patrick

2012-01-01

RNA polymerase (Pol) I contains a 10-subunit catalytic core that is related to the core of Pol II and includes subunit A12.2. In addition, Pol I contains the heterodimeric subcomplexes A14/43 and A49/34.5, which are related to the Pol II subcomplex Rpb4/7 and the Pol II initiation factor TFIIF, respectively. Here we used lysine-lysine crosslinking, mass spectrometry (MS) and modeling based on five crystal structures, to extend the previous homology model of the Pol I core, to confirm the location of A14/43 and to position A12.2 and A49/34.5 on the core. In the resulting model of Pol I, the C-terminal ribbon (C-ribbon) domain of A12.2 reaches the active site via the polymerase pore, like the C-ribbon of the Pol II cleavage factor TFIIS, explaining why the intrinsic RNA cleavage activity of Pol I is strong, in contrast to the weak cleavage activity of Pol II. The A49/34.5 dimerization module resides on the polymerase lobe, like TFIIF, whereas the A49 tWH domain resides above the cleft, resembling parts of TFIIE. This indicates that Pol I and also Pol III are distantly related to a Pol II–TFIIS–TFIIF–TFIIE complex. PMID:22396529

The stability and slow dynamics of spot patterns in the 2D Brusselator model: The effect of open systems and heterogeneities

NASA Astrophysics Data System (ADS)

Tzou, J. C.; Ward, M. J.

2018-06-01

Spot patterns, whereby the activator field becomes spatially localized near certain dynamically-evolving discrete spatial locations in a bounded multi-dimensional domain, is a common occurrence for two-component reaction-diffusion (RD) systems in the singular limit of a large diffusivity ratio. In previous studies of 2-D localized spot patterns for various specific well-known RD systems, the domain boundary was assumed to be impermeable to both the activator and inhibitor, and the reaction-kinetics were assumed to be spatially uniform. As an extension of this previous theory, we use formal asymptotic methods to study the existence, stability, and slow dynamics of localized spot patterns for the singularly perturbed 2-D Brusselator RD model when the domain boundary is only partially impermeable, as modeled by an inhomogeneous Robin boundary condition, or when there is an influx of inhibitor across the domain boundary. In our analysis, we will also allow for the effect of a spatially variable bulk feed term in the reaction kinetics. By applying our extended theory to the special case of one-spot patterns and ring patterns of spots inside the unit disk, we provide a detailed analysis of the effect on spot patterns of these three different sources of heterogeneity. In particular, when there is an influx of inhibitor across the boundary of the unit disk, a ring pattern of spots can become pinned to a ring-radius closer to the domain boundary. Under a Robin condition, a quasi-equilibrium ring pattern of spots is shown to exhibit a novel saddle-node bifurcation behavior in terms of either the inhibitor diffusivity, the Robin constant, or the ambient background concentration. A spatially variable bulk feed term, with a concentrated source of "fuel" inside the domain, is shown to yield a saddle-node bifurcation structure of spot equilibria, which leads to qualitatively new spot-pinning behavior. Results from our asymptotic theory are validated from full numerical simulations of the Brusselator model.

Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds.

PubMed

Chang, Chenchen; Huang, Rong; Yan, Yan; Ma, Hongmin; Dai, Zheng; Zhang, Benying; Deng, Zixin; Liu, Wen; Qu, Xudong

2015-04-01

Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-oriented synthetic pathway, and aromatic-selective AT domains provides a systematic breakthrough toward current knowledge of polyketide extender unit formation and selection, and also opens a route for further engineering of polyketide carbon scaffolds using amino acids.

Incorporation of fragmentation into a volume average solidification model

NASA Astrophysics Data System (ADS)

Zheng, Y.; Wu, M.; Kharicha, A.; Ludwig, A.

2018-01-01

In this study, a volume average solidification model was extended to consider fragmentation as a source of equiaxed crystals during mixed columnar-equiaxed solidification. The formulation suggested for fragmentation is based on two hypotheses: the solute-driven remelting is the dominant mechanism; and the transport of solute-enriched melt through an interdendritic flow in the columnar growth direction is favorable for solute-driven remelting and is the necessary condition for fragment transportation. Furthermore, a test case with Sn-10 wt%Pb melt solidifying vertically downward in a 2D domain (50 × 60 mm2) was calculated to demonstrate the model’s features. Solidification started from the top boundary, and a columnar structure developed initially with its tip growing downward. Furthermore, thermo-solutal convection led to fragmentation in the mushy zone near the columnar tip front. The fragments transported out of the columnar region continued to grow and sink, and finally settled down and piled up in the bottom domain. The growing columnar structure from the top and pile-up of equiaxed crystals from the bottom finally led to a mixed columnar-equiaxed structure, in turn leading to a columnar-to-equiaxed transition (CET). A special macrosegregation pattern was also predicted, in which negative segregation occurred in both columnar and equiaxed regions and a relatively strong positive segregation occurred in the middle domain near the CET line. A parameter study was performed to verify the model capability, and the uncertainty of the model assumption and parameter was discussed.

Modeling of Structural-Acoustic Interaction Using Coupled FE/BE Method and Control of Interior Acoustic Pressure Using Piezoelectric Actuators

NASA Technical Reports Server (NTRS)

Mei, Chuh; Shi, Yacheng

1997-01-01

A coupled finite element (FE) and boundary element (BE) approach is presented to model full coupled structural/acoustic/piezoelectric systems. The dual reciprocity boundary element method is used so that the natural frequencies and mode shapes of the coupled system can be obtained, and to extend this approach to time dependent problems. The boundary element method is applied to interior acoustic domains, and the results are very accurate when compared with limited exact solutions. Structural-acoustic problems are then analyzed with the coupled finite element/boundary element method, where the finite element method models the structural domain and the boundary element method models the acoustic domain. Results for a system consisting of an isotropic panel and a cubic cavity are in good agreement with exact solutions and experiment data. The response of a composite panel backed cavity is then obtained. The results show that the mass and stiffness of piezoelectric layers have to be considered. The coupled finite element and boundary element equations are transformed into modal coordinates, which is more convenient for transient excitation. Several transient problems are solved based on this formulation. Two control designs, a linear quadratic regulator (LQR) and a feedforward controller, are applied to reduce the acoustic pressure inside the cavity based on the equations in modal coordinates. The results indicate that both controllers can reduce the interior acoustic pressure and the plate deflection.

Nonlinear modeling of wave-topography interactions, shear instabilities and shear induced wave breaking using vortex method

NASA Astrophysics Data System (ADS)

Guha, Anirban

2017-11-01

Theoretical studies on linear shear instabilities as well as different kinds of wave interactions often use simple velocity and/or density profiles (e.g. constant, piecewise) for obtaining good qualitative and quantitative predictions of the initial disturbances. Moreover, such simple profiles provide a minimal model to obtain a mechanistic understanding of shear instabilities. Here we have extended this minimal paradigm into nonlinear domain using vortex method. Making use of unsteady Bernoulli's equation in presence of linear shear, and extending Birkhoff-Rott equation to multiple interfaces, we have numerically simulated the interaction between multiple fully nonlinear waves. This methodology is quite general, and has allowed us to simulate diverse problems that can be essentially reduced to the minimal system with interacting waves, e.g. spilling and plunging breakers, stratified shear instabilities (Holmboe, Taylor-Caulfield, stratified Rayleigh), jet flows, and even wave-topography interaction problem like Bragg resonance. We found that the minimal models capture key nonlinear features (e.g. wave breaking features like cusp formation and roll-ups) which are observed in experiments and/or extensive simulations with smooth, realistic profiles.

Extended DBI massive gravity with generalized fiducial metric

NASA Astrophysics Data System (ADS)

Chullaphan, Tossaporn; Tannukij, Lunchakorn; Wongjun, Pitayuth

2015-06-01

We consider an extended model of DBI massive gravity by generalizing the fiducial metric to be an induced metric on the brane corresponding to a domain wall moving in five-dimensional Schwarzschild-Anti-de Sitter spacetime. The model admits all solutions of FLRW metric including flat, closed and open geometries while the original one does not. The background solutions can be divided into two branches namely self-accelerating branch and normal branch. For the self-accelerating branch, the graviton mass plays the role of cosmological constant to drive the late-time acceleration of the universe. It is found that the number degrees of freedom of gravitational sector is not correct similar to the original DBI massive gravity. There are only two propagating degrees of freedom from tensor modes. For normal branch, we restrict our attention to a particular class of the solutions which provides an accelerated expansion of the universe. It is found that the number of degrees of freedom in the model is correct. However, at least one of them is ghost degree of freedom which always present at small scale implying that the theory is not stable.

Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile.

PubMed

Vicario, Alba; Mendoza, Ezequiel; Abellán, Antonio; Scharff, Constance; Medina, Loreta

2017-01-01

We used a battery of genes encoding transcription factors (Pax6, Islet1, Nkx2.1, Lhx6, Lhx5, Lhx9, FoxP2) and neuropeptides to study the extended amygdala in developing zebra finches. We identified different components of the central extended amygdala comparable to those found in mice and chickens, including the intercalated amygdalar cells, the central amygdala, and the lateral bed nucleus of the stria terminalis. Many cells likely originate in the dorsal striatal domain, ventral striatal domain, or the pallidal domain, as is the case in mice and chickens. Moreover, a cell subpopulation of the central extended amygdala appears to originate in the prethalamic eminence. As a general principle, these different cells with specific genetic profiles and embryonic origin form separate or partially intermingled cell corridors along the extended amygdala, which may be involved in different functional pathways. In addition, we identified the medial amygdala of the zebra finch. Like in the chickens and mice, it is located in the subpallium and is rich in cells of pallido-preoptic origin, containing minor subpopulations of immigrant cells from the ventral pallium, alar hypothalamus and prethalamic eminence. We also proposed that the medial bed nucleus of the stria terminalis is composed of several parallel cell corridors with different genetic profile and embryonic origin: preoptic, pallidal, hypothalamic, and prethalamic. Several of these cell corridors with distinct origin express FoxP2, a transcription factor implicated in synaptic plasticity. Our results pave the way for studies using zebra finches to understand the neural basis of social behavior, in which the extended amygdala is involved.

On the performance of piezoelectric harvesters loaded by finite width impulses

NASA Astrophysics Data System (ADS)

Doria, A.; Medè, C.; Desideri, D.; Maschio, A.; Codecasa, L.; Moro, F.

2018-02-01

The response of cantilevered piezoelectric harvesters loaded by finite width impulses of base acceleration is studied analytically in the frequency domain in order to identify the parameters that influence the generated voltage. Experimental tests are then performed on harvesters loaded by hammer impacts. The latter are used to confirm analytical results and to validate a linear finite element (FE) model of a unimorph harvester. The FE model is, in turn, used to extend analytical results to more general harvesters (tapered, inverse tapered, triangular) and to more general impulses (heel strike in human gait). From analytical and numerical results design criteria for improving harvester performance are obtained.

The Twist Tensor Nuclear Norm for Video Completion.

PubMed

Hu, Wenrui; Tao, Dacheng; Zhang, Wensheng; Xie, Yuan; Yang, Yehui

2017-12-01

In this paper, we propose a new low-rank tensor model based on the circulant algebra, namely, twist tensor nuclear norm (t-TNN). The twist tensor denotes a three-way tensor representation to laterally store 2-D data slices in order. On one hand, t-TNN convexly relaxes the tensor multirank of the twist tensor in the Fourier domain, which allows an efficient computation using fast Fourier transform. On the other, t-TNN is equal to the nuclear norm of block circulant matricization of the twist tensor in the original domain, which extends the traditional matrix nuclear norm in a block circulant way. We test the t-TNN model on a video completion application that aims to fill missing values and the experiment results validate its effectiveness, especially when dealing with video recorded by a nonstationary panning camera. The block circulant matricization of the twist tensor can be transformed into a circulant block representation with nuclear norm invariance. This representation, after transformation, exploits the horizontal translation relationship between the frames in a video, and endows the t-TNN model with a more powerful ability to reconstruct panning videos than the existing state-of-the-art low-rank models.

Numerical Investigations of Two Typical Unsteady Flows in Turbomachinery Using the Multi-Passage Model

NASA Astrophysics Data System (ADS)

Zhou, Di; Lu, Zhiliang; Guo, Tongqing; Shen, Ennan

2016-06-01

In this paper, the research on two types of unsteady flow problems in turbomachinery including blade flutter and rotor-stator interaction is made by means of numerical simulation. For the former, the energy method is often used to predict the aeroelastic stability by calculating the aerodynamic work per vibration cycle. The inter-blade phase angle (IBPA) is an important parameter in computation and may have significant effects on aeroelastic behavior. For the latter, the numbers of blades in each row are usually not equal and the unsteady rotor-stator interactions could be strong. An effective way to perform multi-row calculations is the domain scaling method (DSM). These two cases share a common point that the computational domain has to be extended to multi passages (MP) considering their respective features. The present work is aimed at modeling these two issues with the developed MP model. Computational fluid dynamics (CFD) technique is applied to resolve the unsteady Reynolds-averaged Navier-Stokes (RANS) equations and simulate the flow fields. With the parallel technique, the additional time cost due to modeling more passages can be largely decreased. Results are presented on two test cases including a vibrating rotor blade and a turbine stage.

Dynamic modeling of normal faults of the 2016 Central Italy earthquake sequence

NASA Astrophysics Data System (ADS)

Aochi, Hideo

2017-04-01

The earthquake sequence of the Central Italy in 2016 are characterized mainly by the Mw6.0 24th August, Mw5.9 26th October and Mw6.4 30th October as well as two Mw5.4 earthquakes (24th August, 26th October) (catalogue INGV). They all show normal faulting mechanisms corresponding to the Apennines's tectonics. They are aligned briefly along NNW-SSE axis, and they may not be on a single continuous fault plane. Therefore, dynamic rupture modeling of sequences should be carried out supposing co-planar normal multiple segments. We apply a Boundary Domain Method (BDM, Goto and Bielak, GJI, 2008) coupling a boundary integral equation method and a domain-based method, namely a finite difference method in this study. The Mw6.0 24th August earthquake is modeled. We use the basic information of hypocenter position, focal mechanism and potential ruptured dimension from the INGV catalogue and Tinti et al., GRL, 2016), and begin with a simple condition (homogeneous boundary condition). From our preliminary simulations, it is shown that a uniformly extended rupture model does not fit the near-field ground motions and localized heterogeneity would be required.

Salvador has an extended SARAH domain that mediates binding to Hippo kinase.

PubMed

Cairns, Leah; Tran, Thao; Fowl, Brendan H; Patterson, Angela; Kim, Yoo Jin; Bothner, Brian; Kavran, Jennifer M

2018-04-13

The Hippo pathway controls cell proliferation and differentiation through the precisely tuned activity of a core kinase cassette. The activity of Hippo kinase is modulated by interactions between its C-terminal coiled-coil, termed the SARAH domain, and the SARAH domains of either dRassF or Salvador. Here, we wanted to understand the molecular basis of SARAH domain-mediated interactions and their influence on Hippo kinase activity. We focused on Salvador, a positive effector of Hippo activity and the least well-characterized SARAH domain-containing protein. We determined the crystal structure of a complex between Salvador and Hippo SARAH domains from Drosophila This structure provided insight into the organization of the Salvador SARAH domain including a folded N-terminal extension that expands the binding interface with Hippo SARAH domain. We also found that this extension improves the solubility of the Salvador SARAH domain, enhances binding to Hippo, and is unique to Salvador. We therefore suggest expanding the definition of the Salvador SARAH domain to include this extended region. The heterodimeric assembly observed in the crystal was confirmed by cross-linked MS and provided a structural basis for the mutually exclusive interactions of Hippo with either dRassF or Salvador. Of note, Salvador influenced the kinase activity of Mst2, the mammalian Hippo homolog. In co-transfected HEK293T cells, human Salvador increased the levels of Mst2 autophosphorylation and Mst2-mediated phosphorylation of select substrates, whereas Salvador SARAH domain inhibited Mst2 autophosphorylation in vitro These results suggest Salvador enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Helicopter mathematical models and control law development for handling qualities research

NASA Technical Reports Server (NTRS)

Chen, Robert T. N.; Lebacqz, J. Victor; Aiken, Edwin W.; Tischler, Mark B.

1988-01-01

Progress made in joint NASA/Army research concerning rotorcraft flight-dynamics modeling, design methodologies for rotorcraft flight-control laws, and rotorcraft parameter identification is reviewed. Research into these interactive disciplines is needed to develop the analytical tools necessary to conduct flying qualities investigations using both the ground-based and in-flight simulators, and to permit an efficient means of performing flight test evaluation of rotorcraft flying qualities for specification compliance. The need for the research is particularly acute for rotorcraft because of their mathematical complexity, high order dynamic characteristics, and demanding mission requirements. The research in rotorcraft flight-dynamics modeling is pursued along two general directions: generic nonlinear models and nonlinear models for specific rotorcraft. In addition, linear models are generated that extend their utilization from 1-g flight to high-g maneuvers and expand their frequency range of validity for the design analysis of high-gain flight control systems. A variety of methods ranging from classical frequency-domain approaches to modern time-domain control methodology that are used in the design of rotorcraft flight control laws is reviewed. Also reviewed is a study conducted to investigate the design details associated with high-gain, digital flight control systems for combat rotorcraft. Parameter identification techniques developed for rotorcraft applications are reviewed.

Combining the Generic Entity-Attribute-Value Model and Terminological Models into a Common Ontology to Enable Data Integration and Decision Support.

PubMed

Bouaud, Jacques; Guézennec, Gilles; Séroussi, Brigitte

2018-01-01

The integration of clinical information models and termino-ontological models into a unique ontological framework is highly desirable for it facilitates data integration and management using the same formal mechanisms for both data concepts and information model components. This is particularly true for knowledge-based decision support tools that aim to take advantage of all facets of semantic web technologies in merging ontological reasoning, concept classification, and rule-based inferences. We present an ontology template that combines generic data model components with (parts of) existing termino-ontological resources. The approach is developed for the guideline-based decision support module on breast cancer management within the DESIREE European project. The approach is based on the entity attribute value model and could be extended to other domains.

Continuum and three-nucleon force effects on Be 9 energy levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langhammer, Joachim; Navrátil, Petr; Quaglioni, Sofia

2015-02-05

In this paper, we extend the recently proposed ab initio no-core shell model with continuum to include three-nucleon (3N) interactions beyond the few-body domain. The extended approach allows for the assessment of effects of continuum degrees of freedom as well as of the 3N force in ab initio calculations of structure and reaction observables of p- and lower-sd-shell nuclei. As a first application we concentrate on energy levels of the 9Be system for which all excited states lie above the n- 8Be threshold. For all energy levels, the inclusion of the continuum significantly improves the agreement with experiment, which wasmore » an issue in standard no-core shell model calculations. Furthermore, we find the proper treatment of the continuum indispensable for reliable statements about the quality of the adopted 3N interaction from chiral effective field theory. Finally, in particular, we find the 1/2 + resonance energy, which is of astrophysical interest, in good agreement with experiment.« less

Generation of localized patterns in anharmonic lattices with cubic-quintic nonlinearities and fourth-order dispersion via a variational approach

NASA Astrophysics Data System (ADS)

Wamba, Etienne; Tchakoutio Nguetcho, Aurélien S.

2018-05-01

We use the time-dependent variational method to examine the formation of localized patterns in dynamically unstable anharmonic lattices with cubic-quintic nonlinearities and fourth-order dispersion. The governing equation is an extended nonlinear Schrödinger equation known for modified Frankel-Kontorova models of atomic lattices and here derived from an extended Bose-Hubbard model of bosonic lattices with local three-body interactions. In presence of modulated waves, we derive and investigate the ordinary differential equations for the time evolution of the amplitude and phase of dynamical perturbation. Through an effective potential, we find the modulationally unstable domains of the lattice and discuss the effect of the fourth-order dispersion in the dynamics. Direct numerical simulations are performed to support our analytical results, and a good agreement is found. Various types of localized patterns, including breathers and solitonic chirped-like pulses, form in the system as a result of interplay between the cubic-quintic nonlinearities and the second- and fourth-order dispersions.

Analysis of proton wires in the enzyme active site suggests a mechanism of c-di-GMP hydrolysis by the EAL domain phosphodiesterases.

PubMed

Grigorenko, Bella L; Knyazeva, Marina A; Nemukhin, Alexander V

2016-11-01

We report for the first time a hydrolysis mechanism of the cyclic dimeric guanosine monophosphate (c-di-GMP) by the EAL domain phosphodiesterases as revealed by molecular simulations. A model system for the enzyme-substrate complex was prepared on the base of the crystal structure of the EAL domain from the BlrP1 protein complexed with c-di-GMP. The nucleophilic hydroxide generated from the bridging water molecule appeared in a favorable position for attack on the phosphorus atom of c-di-GMP. The most difficult task was to find a pathway for a proton transfer to the O3' atom of c-di-GMP to promote the O3'P bond cleavage. We show that the hydrogen bond network extended over the chain of water molecules in the enzyme active site and the Glu359 and Asp303 side chains provides the relevant proton wires. The suggested mechanism is consistent with the structural, mutagenesis, and kinetic experimental studies on the EAL domain phosphodiesterases. Proteins 2016; 84:1670-1680. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Static and dynamic behaviour of nonlocal elastic bar using integral strain-based and peridynamic models

NASA Astrophysics Data System (ADS)

Challamel, Noël

2018-04-01

The static and dynamic behaviour of a nonlocal bar of finite length is studied in this paper. The nonlocal integral models considered in this paper are strain-based and relative displacement-based nonlocal models; the latter one is also labelled as a peridynamic model. For infinite media, and for sufficiently smooth displacement fields, both integral nonlocal models can be equivalent, assuming some kernel correspondence rules. For infinite media (or finite media with extended reflection rules), it is also shown that Eringen's differential model can be reformulated into a consistent strain-based integral nonlocal model with exponential kernel, or into a relative displacement-based integral nonlocal model with a modified exponential kernel. A finite bar in uniform tension is considered as a paradigmatic static case. The strain-based nonlocal behaviour of this bar in tension is analyzed for different kernels available in the literature. It is shown that the kernel has to fulfil some normalization and end compatibility conditions in order to preserve the uniform strain field associated with this homogeneous stress state. Such a kernel can be built by combining a local and a nonlocal strain measure with compatible boundary conditions, or by extending the domain outside its finite size while preserving some kinematic compatibility conditions. The same results are shown for the nonlocal peridynamic bar where a homogeneous strain field is also analytically obtained in the elastic bar for consistent compatible kinematic boundary conditions at the vicinity of the end conditions. The results are extended to the vibration of a fixed-fixed finite bar where the natural frequencies are calculated for both the strain-based and the peridynamic models.

The Impact of a Ligand Binding on Strand Migration in the SAM-I Riboswitch

PubMed Central

Huang, Wei; Kim, Joohyun; Jha, Shantenu; Aboul-ela, Fareed

2013-01-01

Riboswitches sense cellular concentrations of small molecules and use this information to adjust synthesis rates of related metabolites. Riboswitches include an aptamer domain to detect the ligand and an expression platform to control gene expression. Previous structural studies of riboswitches largely focused on aptamers, truncating the expression domain to suppress conformational switching. To link ligand/aptamer binding to conformational switching, we constructed models of an S-adenosyl methionine (SAM)-I riboswitch RNA segment incorporating elements of the expression platform, allowing formation of an antiterminator (AT) helix. Using Anton, a computer specially developed for long timescale Molecular Dynamics (MD), we simulated an extended (three microseconds) MD trajectory with SAM bound to a modeled riboswitch RNA segment. Remarkably, we observed a strand migration, converting three base pairs from an antiterminator (AT) helix, characteristic of the transcription ON state, to a P1 helix, characteristic of the OFF state. This conformational switching towards the OFF state is observed only in the presence of SAM. Among seven extended trajectories with three starting structures, the presence of SAM enhances the trend towards the OFF state for two out of three starting structures tested. Our simulation provides a visual demonstration of how a small molecule (<500 MW) binding to a limited surface can trigger a large scale conformational rearrangement in a 40 kDa RNA by perturbing the Free Energy Landscape. Such a mechanism can explain minimal requirements for SAM binding and transcription termination for SAM-I riboswitches previously reported experimentally. PMID:23704854

Frequency domain FIR and IIR adaptive filters

NASA Technical Reports Server (NTRS)

Lynn, D. W.

1990-01-01

A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.

Development of a health information technology acceptance model using consumers' health behavior intention.

PubMed

Kim, Jeongeun; Park, Hyeoun-Ae

2012-10-01

For effective health promotion using health information technology (HIT), it is mandatory that health consumers have the behavioral intention to measure, store, and manage their own health data. Understanding health consumers' intention and behavior is needed to develop and implement effective and efficient strategies. To develop and verify the extended Technology Acceptance Model (TAM) in health care by describing health consumers' behavioral intention of using HIT. This study used a cross-sectional descriptive correlational design. We extended TAM by adding more antecedents and mediating variables to enhance the model's explanatory power and to make it more applicable to health consumers' behavioral intention. Additional antecedents and mediating variables were added to the hypothetical model, based on their theoretical relevance, from the Health Belief Model and theory of planned behavior, along with the TAM. We undertook structural equation analysis to examine the specific nature of the relationship involved in understanding consumers' use of HIT. Study participants were 728 members recruited from three Internet health portals in Korea. Data were collected by a Web-based survey using a structured self-administered questionnaire. The overall fitness indices for the model developed in this study indicated an acceptable fit of the model. All path coefficients were statistically significant. This study showed that perceived threat, perceived usefulness, and perceived ease of use significantly affected health consumers' attitude and behavioral intention. Health consumers' health status, health belief and concerns, subjective norm, HIT characteristics, and HIT self-efficacy had a strong indirect impact on attitude and behavioral intention through the mediators of perceived threat, perceived usefulness, and perceived ease of use. An extended TAM in the HIT arena was found to be valid to describe health consumers' behavioral intention. We categorized the concepts in the extended TAM into 3 domains: health zone, information zone, and technology zone.

Internal Versus External DSLs for Trace Analysis: Extended Abstract

NASA Technical Reports Server (NTRS)

Barringer, Howard; Havelund, Klaus

2011-01-01

This tutorial explores the design and implementation issues arising in the development of domain-specific languages for trace analysis. It introduces the audience to the general concepts underlying such special-purpose languages building upon the authors' own experiences in developing both external domain specific languages and systems, such as EAGLE, HAWK, RULER and LOGSCOPE, and the more recent internal domain-specific language and system TRACECONTRACT within the SCALA language.

The 5'×5' global geoid model GGM2016

NASA Astrophysics Data System (ADS)

Shen, WenBin; Han, Jiancheng

2016-04-01

We provide an updated 5'×5' global geoid model GGM2016, which is determined based on the shallow layer method (Shen 2006). We choose an inner surface S below the EGM2008 geoid, and the layer bounded by the inner surface S and the Earth's geographical surface E is referred to as the shallow layer. The Earth's geographical surface E is determined by the digital topographic model DTM2006.0 combining with the DNSC2008 mean sea surface. We determine the 3D shallow layer model (SLM) using the refined crust density model CRUST1.0-5min, which is an improved 5'×5' density model of the CRUST1.0 with taking into account the corrections of the areas covered by ice sheets and the land-ocean crossing regions. Based on the SLM and the gravity field EGM2008 defined outside the Earth's geographical surface E, we determine the gravity field EGM2008S defined in the region outside the inner surface S, extending the gravity field's definition domain from the domain outside E to the domain outside S. Based on the geodetic equation W(P)=W0, where W0 is the geopotential constant on the geoid, we determine a 5'×5' global geoid model GGM2016, which provides both the 5'×5' grid values and spherical harmonic coefficient expressions. Comparisons show that the GGM2016 fits the globally available GPS/leveling points better than the EGM2008 geoid. This study is supported by National 973 Project China (grant Nos. 2013CB733301 and 2013CB733305), NSFC (grant Nos. 41174011, 41210006, 41429401, 41128003, 41021061).

The interdomain interface in bifunctional enzyme protein 3/4A (NS3/4A) regulates protease and helicase activities.

PubMed

Aydin, Cihan; Mukherjee, Sourav; Hanson, Alicia M; Frick, David N; Schiffer, Celia A

2013-12-01

Hepatitis C (HCV) protein 3/4A (NS3/4A) is a bifunctional enzyme comprising two separate domains with protease and helicase activities, which are essential for viral propagation. Both domains are stable and have enzymatic activity separately, and the relevance and implications of having protease and helicase together as a single protein remains to be explored. Altered in vitro activities of isolated domains compared with the full-length NS3/4A protein suggest the existence of interdomain communication. The molecular mechanism and extent of this communication was investigated by probing the domain-domain interface observed in HCV NS3/4A crystal structures. We found in molecular dynamics simulations that the two domains of NS3/4A are dynamically coupled through the interface. Interestingly, mutations designed to disrupt this interface did not hinder the catalytic activities of either domain. In contrast, substrate cleavage and DNA unwinding by these mutants were mostly enhanced compared with the wild-type protein. Disrupting the interface did not significantly alter RNA unwinding activity; however, the full-length protein was more efficient in RNA unwinding than the isolated protease domain, suggesting a more direct role in RNA processing independent of the interface. Our findings suggest that HCV NS3/4A adopts an "extended" catalytically active conformation, and interface formation acts as a switch to regulate activity. We propose a unifying model connecting HCV NS3/4A conformational states and protease and helicase function, where interface formation and the dynamic interplay between the two enzymatic domains of HCV NS3/4A potentially modulate the protease and helicase activities in vivo. © 2013 The Protein Society.

High-speed extended-term time-domain simulation for online cascading analysis of power system

NASA Astrophysics Data System (ADS)

Fu, Chuan

A high-speed extended-term (HSET) time domain simulator (TDS), intended to become a part of an energy management system (EMS), has been newly developed for use in online extended-term dynamic cascading analysis of power systems. HSET-TDS includes the following attributes for providing situational awareness of high-consequence events: (i) online analysis, including n-1 and n-k events, (ii) ability to simulate both fast and slow dynamics for 1-3 hours in advance, (iii) inclusion of rigorous protection-system modeling, (iv) intelligence for corrective action ID, storage, and fast retrieval, and (v) high-speed execution. Very fast on-line computational capability is the most desired attribute of this simulator. Based on the process of solving algebraic differential equations describing the dynamics of power system, HSET-TDS seeks to develop computational efficiency at each of the following hierarchical levels, (i) hardware, (ii) strategies, (iii) integration methods, (iv) nonlinear solvers, and (v) linear solver libraries. This thesis first describes the Hammer-Hollingsworth 4 (HH4) implicit integration method. Like the trapezoidal rule, HH4 is symmetrically A-Stable but it possesses greater high-order precision (h4 ) than the trapezoidal rule. Such precision enables larger integration steps and therefore improves simulation efficiency for variable step size implementations. This thesis provides the underlying theory on which we advocate use of HH4 over other numerical integration methods for power system time-domain simulation. Second, motivated by the need to perform high speed extended-term time domain simulation (HSET-TDS) for on-line purposes, this thesis presents principles for designing numerical solvers of differential algebraic systems associated with power system time-domain simulation, including DAE construction strategies (Direct Solution Method), integration methods(HH4), nonlinear solvers(Very Dishonest Newton), and linear solvers(SuperLU). We have implemented a design appropriate for HSET-TDS, and we compare it to various solvers, including the commercial grade PSSE program, with respect to computational efficiency and accuracy, using as examples the New England 39 bus system, the expanded 8775 bus system, and PJM 13029 buses system. Third, we have explored a stiffness-decoupling method, intended to be part of parallel design of time domain simulation software for super computers. The stiffness-decoupling method is able to combine the advantages of implicit methods (A-stability) and explicit method(less computation). With the new stiffness detection method proposed herein, the stiffness can be captured. The expanded 975 buses system is used to test simulation efficiency. Finally, several parallel strategies for super computer deployment to simulate power system dynamics are proposed and compared. Design A partitions the task via scale with the stiffness decoupling method, waveform relaxation, and parallel linear solver. Design B partitions the task via the time axis using a highly precise integration method, the Kuntzmann-Butcher Method - order 8 (KB8). The strategy of partitioning events is designed to partition the whole simulation via the time axis through a simulated sequence of cascading events. For all strategies proposed, a strategy of partitioning cascading events is recommended, since the sub-tasks for each processor are totally independent, and therefore minimum communication time is needed.

Uranium nitride: a cubic antiferromagnet with anisotropic critical behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buyers, W J.L.; Holden, T M; Svensson, E C

1977-11-01

Highly anisotropic critical scattering associated with the transition at T/sub N/ = 49.5 K to the type-I antiferromagnetic structure has been observed in uranium nitride. The transverse susceptibility is found to be unobservably small. The longitudinal susceptibility diverges at T/sub N/ and its anisotropy shows that the spins within the (001) ferromagnetic sheets of the (001) domain are much more highly correlated than they are with the spins lying in adjacent (001) sheets. The correlation range within the sheets is much greater than that expected for a Heisenberg system with the same T/sub N/. The rod-like scattering extended along themore » spin and domain direction is reminiscent of two-dimensional behavior. The results are inconsistent with a simple localized model and may reflect the itinerant nature of the 5f electrons.« less

Geometric constraints for shape and topology optimization in architectural design

NASA Astrophysics Data System (ADS)

Dapogny, Charles; Faure, Alexis; Michailidis, Georgios; Allaire, Grégoire; Couvelas, Agnes; Estevez, Rafael

2017-06-01

This work proposes a shape and topology optimization framework oriented towards conceptual architectural design. A particular emphasis is put on the possibility for the user to interfere on the optimization process by supplying information about his personal taste. More precisely, we formulate three novel constraints on the geometry of shapes; while the first two are mainly related to aesthetics, the third one may also be used to handle several fabrication issues that are of special interest in the device of civil structures. The common mathematical ingredient to all three models is the signed distance function to a domain, and its sensitivity analysis with respect to perturbations of this domain; in the present work, this material is extended to the case where the ambient space is equipped with an anisotropic metric tensor. Numerical examples are discussed in two and three space dimensions.

An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

NASA Technical Reports Server (NTRS)

Foyle, David C.; Goodman, Allen; Hooley, Becky L.

2003-01-01

An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manjunath, Naren; Samajdar, Rhine; Jain, Sudhir R., E-mail: srjain@barc.gov.in

Recently, the nodal domain counts of planar, integrable billiards with Dirichlet boundary conditions were shown to satisfy certain difference equations in Samajdar and Jain (2014). The exact solutions of these equations give the number of domains explicitly. For complete generality, we demonstrate this novel formulation for three additional separable systems and thus extend the statement to all integrable billiards.

Extension theorems for homogenization on lattice structures

NASA Technical Reports Server (NTRS)

Miller, Robert E.

1992-01-01

When applying homogenization techniques to problems involving lattice structures, it is necessary to extend certain functions defined on a perforated domain to a simply connected domain. This paper provides general extension operators which preserve bounds on derivatives of order l. Only the special case of honeycomb structures is considered.

The Interplay between Executive Control and Motor Functioning in Williams Syndrome

ERIC Educational Resources Information Center

Hocking, Darren R.; Thomas, Daniel; Menant, Jasmine C.; Porter, Melanie A.; Smith, Stuart; Lord, Stephen R.; Cornish, Kim M.

2013-01-01

Previous studies suggest that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show specific weaknesses in visual attention and response inhibition within the visuospatial domain. Here we examine the extent to which impairments in attentional control extend to the visuomotor domain using a…

Hypertext Interchange Using ICA.

ERIC Educational Resources Information Center

Rada, Roy; And Others

1995-01-01

Discusses extended ICA (Integrated Chameleon Architecture), a public domain toolset for generating text-to-hypertext translators. A system called SGML-MUCH has been developed using E-ICA (Extended Integrated Chameleon Architecture) and is presented as a case study with converters for the hypertext systems MUCH, Guide, Hyperties, and Toolbook.…

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

ERIC Educational Resources Information Center

Vaidya, Chandan J.; Stollstorff, Melanie

2008-01-01

Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

Brain signal variability as a window into the bidirectionality between music and language processing: moving from a linear to a nonlinear model

PubMed Central

Hutka, Stefanie; Bidelman, Gavin M.; Moreno, Sylvain

2013-01-01

There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain’s processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer. PMID:24454295

Brain signal variability as a window into the bidirectionality between music and language processing: moving from a linear to a nonlinear model.

PubMed

Hutka, Stefanie; Bidelman, Gavin M; Moreno, Sylvain

2013-12-30

There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain's processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer.

Interactions of the SAP Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Carra, Claudio; Huff, Janice; Pluth, Janice M.; Cucinotta, Francis A.

2007-01-01

NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku70/80 complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The SAP domain of Ku70 (residues 556-609), contains an a helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the SAP/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the SAP domain of Ku70 and a 10 base pairs DNA duplex. Large-scale conformational changes were observed and some putative binding modes were suggested based on energetic analysis. These modes are consistent with previous experimental investigations. In addition, the results indicate that cooperation of SAP with other domains of Ku70/80 is necessary to explain the high affinity of binding as observed in experiments.

Free energy landscapes for initiation and branching of protein aggregation.

PubMed

Zheng, Weihua; Schafer, Nicholas P; Wolynes, Peter G

2013-12-17

Experiments on artificial multidomain protein constructs have probed the early stages of aggregation processes, but structural details of the species that initiate aggregation remain elusive. Using the associative-memory, water-mediated, structure and energy model known as AWSEM, a transferable coarse-grained protein model, we performed simulations of fused constructs composed of up to four copies of the Titin I27 domain or its mutant I27* (I59E). Free energy calculations enable us to quantify the conditions under which such multidomain constructs will spontaneously misfold. Consistent with experimental results, the dimer of I27 is found to be the smallest spontaneously misfolding construct. Our results show how structurally distinct misfolded states can be stabilized under different thermodynamic conditions, and this result provides a plausible link between the single-molecule misfolding experiments under native conditions and aggregation experiments under denaturing conditions. The conditions for spontaneous misfolding are determined by the interplay among temperature, effective local protein concentration, and the strength of the interdomain interactions. Above the folding temperature, fusing additional domains to the monomer destabilizes the native state, and the entropically stabilized amyloid-like state is favored. Because it is primarily energetically stabilized, the domain-swapped state is more likely to be important under native conditions. Both protofibril-like and branching structures are found in annealing simulations starting from extended structures, and these structures suggest a possible connection between the existence of multiple amyloidogenic segments in each domain and the formation of branched, amorphous aggregates as opposed to linear fibrillar structures.

Lithospheric extension near Lake Mead, Nevada - A model for ductile flow in the lower crust

NASA Technical Reports Server (NTRS)

Kruse, Sarah; Mcnutt, Marcia; Phipps-Morgan, Jason; Royden, Leigh

1991-01-01

Small variations in gravity anomalies and topographic elevation observed in areas that have undergone highly variable amounts of upper crustal thinning can be satisfactorily explained by ductile flow of lower crustal material under the proper conditions. The boundary between the unextended Colorado Plateau and a strongly extended domain in the Basin and Range Province in the Lake Mead (Nevada) region is examined. Finite element modeling of Newtonian flow and power law creep shows that flow over the length scale of the eastern Basin and Range (500) km or more) corresponding to upper crustal extension by a factor of 1.4-3 over 10 million years requires effective viscosities less than 10 to the 18th - 10 to the 20th Pa s for ductile channels 10-25 km thick. Modeling suggests that these effective viscosities may be sustained by lower crustal material deforming at laboratory-derived power law creep rates. The longer-scale flow may require elevated crustal temperatures (more than 700 C), depending on the composition and material properties assumed. Under the boundary conditions assumed in this study the linear viscous flow models yield a satisfactory approximation to deformation by power law creep. This work suggests that flow in the lower crust may be a viable mechanism for producing small variations in total crustal thickness between strongly extended and less extended regions, and thereby explaining the relative uniformity in gravity and topography between such regions.

The effect of pump depletion on reversible photodegradation

NASA Astrophysics Data System (ADS)

Anderson, Benjamin; Hung, Sheng-Ting; Kuzyk, Mark G.

2014-05-01

We model the effect of pump depletion on reversible photodegradation using the extended domain model [Anderson and Kuzyk, arXiv:1309.5176v1, 2013] and the Beer-Lambert law. We find that neglecting pump absorption in the analysis of the linear optical transmittance leads to an underestimate of the degree and rate of photodegradation. The model is used to accurately measure the molecular absorbance cross sections of the three species involved in photodegradation of disperse orange 11 dye in (poly)methyl-methacralate polymer (DO11/PMMA). Finally we find that the processing history of a dye-doped polymer affects reversible photodegradation, with polymerized monomer solutions of DO11 being more photostable than those prepared from solvent evaporated dye-polymer solutions.

Extending enterprise architecture modelling with business goals and requirements

NASA Astrophysics Data System (ADS)

Engelsman, Wilco; Quartel, Dick; Jonkers, Henk; van Sinderen, Marten

2011-02-01

The methods for enterprise architecture (EA), such as The Open Group Architecture Framework, acknowledge the importance of requirements modelling in the development of EAs. Modelling support is needed to specify, document, communicate and reason about goals and requirements. The current modelling techniques for EA focus on the products, services, processes and applications of an enterprise. In addition, techniques may be provided to describe structured requirements lists and use cases. Little support is available however for modelling the underlying motivation of EAs in terms of stakeholder concerns and the high-level goals that address these concerns. This article describes a language that supports the modelling of this motivation. The definition of the language is based on existing work on high-level goal and requirements modelling and is aligned with an existing standard for enterprise modelling: the ArchiMate language. Furthermore, the article illustrates how EA can benefit from analysis techniques from the requirements engineering domain.

Delay differential analysis of time series.

PubMed

Lainscsek, Claudia; Sejnowski, Terrence J

2015-03-01

Nonlinear dynamical system analysis based on embedding theory has been used for modeling and prediction, but it also has applications to signal detection and classification of time series. An embedding creates a multidimensional geometrical object from a single time series. Traditionally either delay or derivative embeddings have been used. The delay embedding is composed of delayed versions of the signal, and the derivative embedding is composed of successive derivatives of the signal. The delay embedding has been extended to nonuniform embeddings to take multiple timescales into account. Both embeddings provide information on the underlying dynamical system without having direct access to all the system variables. Delay differential analysis is based on functional embeddings, a combination of the derivative embedding with nonuniform delay embeddings. Small delay differential equation (DDE) models that best represent relevant dynamic features of time series data are selected from a pool of candidate models for detection or classification. We show that the properties of DDEs support spectral analysis in the time domain where nonlinear correlation functions are used to detect frequencies, frequency and phase couplings, and bispectra. These can be efficiently computed with short time windows and are robust to noise. For frequency analysis, this framework is a multivariate extension of discrete Fourier transform (DFT), and for higher-order spectra, it is a linear and multivariate alternative to multidimensional fast Fourier transform of multidimensional correlations. This method can be applied to short or sparse time series and can be extended to cross-trial and cross-channel spectra if multiple short data segments of the same experiment are available. Together, this time-domain toolbox provides higher temporal resolution, increased frequency and phase coupling information, and it allows an easy and straightforward implementation of higher-order spectra across time compared with frequency-based methods such as the DFT and cross-spectral analysis.

Development of a Health Information Technology Acceptance Model Using Consumers’ Health Behavior Intention

PubMed Central

2012-01-01

Background For effective health promotion using health information technology (HIT), it is mandatory that health consumers have the behavioral intention to measure, store, and manage their own health data. Understanding health consumers’ intention and behavior is needed to develop and implement effective and efficient strategies. Objective To develop and verify the extended Technology Acceptance Model (TAM) in health care by describing health consumers’ behavioral intention of using HIT. Methods This study used a cross-sectional descriptive correlational design. We extended TAM by adding more antecedents and mediating variables to enhance the model’s explanatory power and to make it more applicable to health consumers’ behavioral intention. Additional antecedents and mediating variables were added to the hypothetical model, based on their theoretical relevance, from the Health Belief Model and theory of planned behavior, along with the TAM. We undertook structural equation analysis to examine the specific nature of the relationship involved in understanding consumers’ use of HIT. Study participants were 728 members recruited from three Internet health portals in Korea. Data were collected by a Web-based survey using a structured self-administered questionnaire. Results The overall fitness indices for the model developed in this study indicated an acceptable fit of the model. All path coefficients were statistically significant. This study showed that perceived threat, perceived usefulness, and perceived ease of use significantly affected health consumers’ attitude and behavioral intention. Health consumers’ health status, health belief and concerns, subjective norm, HIT characteristics, and HIT self-efficacy had a strong indirect impact on attitude and behavioral intention through the mediators of perceived threat, perceived usefulness, and perceived ease of use. Conclusions An extended TAM in the HIT arena was found to be valid to describe health consumers’ behavioral intention. We categorized the concepts in the extended TAM into 3 domains: health zone, information zone, and technology zone. PMID:23026508

Four Amino Acids within a Tandem QxVx Repeat in a Predicted Extended α-Helix of the Smad-Binding Domain of Sip1 Are Necessary for Binding to Activated Smad Proteins

PubMed Central

Conidi, Andrea; van den Berghe, Veronique; Leslie, Kris; Stryjewska, Agata; Xue, Hua; Chen, Ye-Guang; Seuntjens, Eve; Huylebroeck, Danny

2013-01-01

The zinc finger transcription factor Smad-interacting protein-1 (Sip1; Zeb2, Zfhx1b) plays an important role during vertebrate embryogenesis in various tissues and differentiating cell types, and during tumorigenesis. Previous biochemical analysis suggests that interactions with several partner proteins, including TGFβ family receptor-activated Smads, regulate the activities of Sip1 in the nucleus both as a DNA-binding transcriptional repressor and activator. Using a peptide aptamer approach we mapped in Sip1 its Smad-binding domain (SBD), initially defined as a segment of 51 amino acids, to a shorter stretch of 14 amino acids within this SBD. Modelling suggests that this short SBD stretch is part of an extended α-helix that may fit the binding to a hydrophobic corridor within the MH2 domain of activated Smads. Four amino acids (two polar Q residues and two non-polar V residues) that form the tandem repeat (QxVx)2 in this 14-residue stretch were found to be crucial for binding to both TGFβ/Nodal/Activin-Smads and BMP-Smads. A full-length Sip1 with collective mutation of these Q and V residues (to A) no longer binds to Smads, while it retains its binding activity to its cognate bipartite target DNA sequence. This missense mutant Sip1(AxAx)2 provides a new molecular tool to identify SBD (in)dependent target genes in Sip1-controlled TGFβ and/or BMP (de)regulated cellular, developmental and pathological processes. PMID:24146916

Population shuffling between ground and high energy excited states

PubMed Central

Sabo, T Michael; Trent, John O; Lee, Donghan

2015-01-01

Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a “top-down” temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche− rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. PMID:26316263

Population shuffling between ground and high energy excited states.

PubMed

Sabo, T Michael; Trent, John O; Lee, Donghan

2015-11-01

Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a "top-down" temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche - rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. © 2015 The Protein Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei, Huan; Baker, Nathan A.; Li, Xiantao

We present a data-driven approach to determine the memory kernel and random noise of the generalized Langevin equation. To facilitate practical implementations, we parameterize the kernel function in the Laplace domain by a rational function, with coefficients directly linked to the equilibrium statistics of the coarse-grain variables. Further, we show that such an approximation can be constructed to arbitrarily high order. Within these approximations, the generalized Langevin dynamics can be embedded in an extended stochastic model without memory. We demonstrate how to introduce the stochastic noise so that the fluctuation-dissipation theorem is exactly satisfied.

Generalized group field theories and quantum gravity transition amplitudes

NASA Astrophysics Data System (ADS)

Oriti, Daniele

2006-03-01

We construct a generalized formalism for group field theories, in which the domain of the field is extended to include additional proper time variables, as well as their conjugate mass variables. This formalism allows for different types of quantum gravity transition amplitudes in perturbative expansion, and we show how both causal spin foam models and the usual a-causal ones can be derived from it, within a sum over triangulations of all topologies. We also highlight the relation of the so-derived causal transition amplitudes with simplicial gravity actions.

Porting LAMMPS to GPUs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, William Michael; Plimpton, Steven James; Wang, Peng

2010-03-01

LAMMPS is a classical molecular dynamics code, and an acronym for Large-scale Atomic/Molecular Massively Parallel Simulator. LAMMPS has potentials for soft materials (biomolecules, polymers) and solid-state materials (metals, semiconductors) and coarse-grained or mesoscopic systems. It can be used to model atoms or, more generically, as a parallel particle simulator at the atomic, meso, or continuum scale. LAMMPS runs on single processors or in parallel using message-passing techniques and a spatial-decomposition of the simulation domain. The code is designed to be easy to modify or extend with new functionality.

Extended depth of focus adaptive optics spectral domain optical coherence tomography

PubMed Central

Sasaki, Kazuhiro; Kurokawa, Kazuhiro; Makita, Shuichi; Yasuno, Yoshiaki

2012-01-01

We present an adaptive optics spectral domain optical coherence tomography (AO-SDOCT) with a long focal range by active phase modulation of the pupil. A long focal range is achieved by introducing AO-controlled third-order spherical aberration (SA). The property of SA and its effects on focal range are investigated in detail using the Huygens-Fresnel principle, beam profile measurement and OCT imaging of a phantom. The results indicate that the focal range is extended by applying SA, and the direction of extension can be controlled by the sign of applied SA. Finally, we demonstrated in vivo human retinal imaging by altering the applied SA. PMID:23082278

Extended depth of focus adaptive optics spectral domain optical coherence tomography.

PubMed

Sasaki, Kazuhiro; Kurokawa, Kazuhiro; Makita, Shuichi; Yasuno, Yoshiaki

2012-10-01

We present an adaptive optics spectral domain optical coherence tomography (AO-SDOCT) with a long focal range by active phase modulation of the pupil. A long focal range is achieved by introducing AO-controlled third-order spherical aberration (SA). The property of SA and its effects on focal range are investigated in detail using the Huygens-Fresnel principle, beam profile measurement and OCT imaging of a phantom. The results indicate that the focal range is extended by applying SA, and the direction of extension can be controlled by the sign of applied SA. Finally, we demonstrated in vivo human retinal imaging by altering the applied SA.

Extending the limits of complex learning in organic amnesia: computer training in a vocational domain.

PubMed

Glisky, E L; Schacter, D L

1989-01-01

This study explored the limits of learning that could be achieved by an amnesic patient in a complex real-world domain. Using a cuing procedure known as the method of vanishing cues, a severely amnesic encephalitic patient was taught over 250 discrete pieces of new information concerning the rules and procedures for performing a task involving data entry into a computer. Subsequently, she was able to use this acquired knowledge to perform the task accurately and efficiently in the workplace. These results suggest that amnesic patients' preserved learning abilities can be extended well beyond what has been reported previously.

Time domain analysis of thin-wire antennas over lossy ground using the reflection-coefficient approximation

NASA Astrophysics Data System (ADS)

FernáNdez Pantoja, M.; Yarovoy, A. G.; Rubio Bretones, A.; GonzáLez GarcíA, S.

2009-12-01

This paper presents a procedure to extend the methods of moments in time domain for the transient analysis of thin-wire antennas to include those cases where the antennas are located over a lossy half-space. This extended technique is based on the reflection coefficient (RC) approach, which approximates the fields incident on the ground interface as plane waves and calculates the time domain RC using the inverse Fourier transform of Fresnel equations. The implementation presented in this paper uses general expressions for the RC which extend its range of applicability to lossy grounds, and is proven to be accurate and fast for antennas located not too near to the ground. The resulting general purpose procedure, able to treat arbitrarily oriented thin-wire antennas, is appropriate for all kind of half-spaces, including lossy cases, and it has turned out to be as computationally fast solving the problem of an arbitrary ground as dealing with a perfect electric conductor ground plane. Results show a numerical validation of the method for different half-spaces, paying special attention to the influence of the antenna to ground distance in the accuracy of the results.

Cell Adhesion Molecule L1 in Folded (Horseshoe) and Extended Conformations

PubMed Central

Schürmann, Gregor; Haspel, Jeffrey; Grumet, Martin; Erickson, Harold P.

2001-01-01

We have investigated the structure of the cell adhesion molecule L1 by electron microscopy. We were particularly interested in the conformation of the four N-terminal immunoglobulin domains, because x-ray diffraction showed that these domains are bent into a horseshoe shape in the related molecules hemolin and axonin-1. Surprisingly, rotary-shadowed specimens showed the molecules to be elongated, with no indication of the horseshoe shape. However, sedimentation data suggested that these domains of L1 were folded into a compact shape in solution; therefore, this prompted us to look at the molecules by an alternative technique, negative stain. The negative stain images showed a compact shape consistent with the expected horseshoe conformation. We speculate that in rotary shadowing the contact with the mica caused a distortion of the protein, weakening the bonds forming the horseshoe and permitting the molecule to extend. We have thus confirmed that the L1 molecule is primarily in the horseshoe conformation in solution, and we have visualized for the first time its opening into an extended conformation. Our study resolves conflicting interpretations from previous electron microscopy studies of L1. PMID:11408583

Direct observation of interlocked domain walls and topological four-state vortex-like domain patterns in multiferroic YMnO{sub 3} single crystal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Lei; School of Materials Science and Engineering, Dalian Jiaotong University, Dalian, Liaoning 116028; Wang, Yumei, E-mail: wangym@iphy.ac.cn

2015-03-16

Using the advanced spherical aberration-corrected high angle annular dark field scanning transmission electron microscope imaging techniques, we investigated atomic-scale structural features of domain walls and domain patterns in YMnO{sub 3} single crystal. Three different types of interlocked ferroelectric-antiphase domain walls and two abnormal topological four-state vortex-like domain patterns are identified. Each ferroelectric domain wall is accompanied by a translation vector, i.e., 1/6[210] or −1/6[210], demonstrating its interlocked nature. Different from the four-state vortex domain patterns caused by a partial edge dislocation, two four-state vortex-like domain configurations have been obtained at atomic level. These observed phenomena can further extend our understandingmore » of the fascinating vortex domain patterns in multiferroic hexagonal rare-earth manganites.« less

Internal Domains of Natural Porous Media Revealed: Critical Locations for Transport, Storage, and Chemical Reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zachara, John M.; Brantley, Susan L.; Chorover, Jon D.

2016-03-16

Internal pore domains exist within rocks, lithic fragments, subsurface sediments and soil aggregates. These domains, which we term internal domains in porous media (IDPM), contain a significant fraction of their porosity as nanopores, dominate the reactive surface area of diverse porous media types, and are important locations for chemical reactivity and hydrocarbon storage. Traditionally difficult to interrogate, advances in instrumentation and imaging methods are providing new insights on the physical structures and chemical attributes of IDPM. In this review we: discuss analytical methods to characterize IDPM, evaluate what has been learned about their size distributions, connectivity, and extended structures; determinemore » whether they exhibit unique chemical reactivity; and assess potential for their inclusion in reactive transport models. Three key findings are noteworthy. 1) A combination of methods now allows complete characterization of the porosity spectrum of natural materials and its connectivity; while imaging microscopies are providing three dimensional representations of the interconnected pore network. 2) Chemical reactivity in pores <10 nm is expected to be different from micro and macropores, yet research performed to date is inconclusive on the nature, direction, and magnitude of effect. 3) Existing continuum reactive transport models treat IDPM as a sub-grid feature with average, empirical, scale-dependent parameters; and are not formulated to include detailed information on pore networks. Overall we find that IDPM are key features controlling hydrocarbon release from shales in hydrofracking systems, organic matter stabilization and recalcitrance in soil, weathering and soil formation, and long term inorganic and organic contaminant behavior in the vadose zone and groundwater. We conclude with an assessment of impactful research opportunities to advance understanding of IDPM, and to incorporate their important effects in reactive transport models for improved environmental simulation and prediction.« less

Substituted cysteine accessibility method (SCAM) analysis of the transport domain of human concentrative nucleoside transporter 3 (hCNT3) and other family members reveals features of structural and functional importance

PubMed Central

Mulinta, Ras; Yao, Sylvia Y. M.; Ng, Amy M. L.; Cass, Carol E.; Young, James D.

2017-01-01

The human SLC28 family of concentrative nucleoside transporter (CNT) proteins has three members: hCNT1, hCNT2, and hCNT3. Na+-coupled hCNT1 and hCNT2 transport pyrimidine and purine nucleosides, respectively, whereas hCNT3 transports both pyrimidine and purine nucleosides utilizing Na+ and/or H+ electrochemical gradients. Escherichia coli CNT family member NupC resembles hCNT1 in permeant selectivity but is H+-coupled. Using heterologous expression in Xenopus oocytes and the engineered cysteine-less hCNT3 protein hCNT3(C−), substituted cysteine accessibility method analysis with the membrane-impermeant thiol reactive reagent p-chloromercuribenzene sulfonate was performed on the transport domain (interfacial helix 2, hairpin 1, putative transmembrane domain (TM) 7, and TM8), as well as TM9 of the scaffold domain of the protein. This systematic scan of the entire C-terminal half of hCNT3(C−) together with parallel studies of the transport domain of wild-type hCNT1 and the corresponding TMs of cysteine-less NupC(C−) yielded results that validate the newly developed structural homology model of CNT membrane architecture for human CNTs, revealed extended conformationally mobile regions within transport-domain TMs, identified pore-lining residues of functional importance, and provided evidence of an emerging novel elevator-type mechanism of transporter function. PMID:28385889

Frequency domain analysis of noise in simple gene circuits

NASA Astrophysics Data System (ADS)

Cox, Chris D.; McCollum, James M.; Austin, Derek W.; Allen, Michael S.; Dar, Roy D.; Simpson, Michael L.

2006-06-01

Recent advances in single cell methods have spurred progress in quantifying and analyzing stochastic fluctuations, or noise, in genetic networks. Many of these studies have focused on identifying the sources of noise and quantifying its magnitude, and at the same time, paying less attention to the frequency content of the noise. We have developed a frequency domain approach to extract the information contained in the frequency content of the noise. In this article we review our work in this area and extend it to explicitly consider sources of extrinsic and intrinsic noise. First we review applications of the frequency domain approach to several simple circuits, including a constitutively expressed gene, a gene regulated by transitions in its operator state, and a negatively autoregulated gene. We then review our recent experimental study, in which time-lapse microscopy was used to measure noise in the expression of green fluorescent protein in individual cells. The results demonstrate how changes in rate constants within the gene circuit are reflected in the spectral content of the noise in a manner consistent with the predictions derived through frequency domain analysis. The experimental results confirm our earlier theoretical prediction that negative autoregulation not only reduces the magnitude of the noise but shifts its content out to higher frequency. Finally, we develop a frequency domain model of gene expression that explicitly accounts for extrinsic noise at the transcriptional and translational levels. We apply the model to interpret a shift in the autocorrelation function of green fluorescent protein induced by perturbations of the translational process as a shift in the frequency spectrum of extrinsic noise and a decrease in its weighting relative to intrinsic noise.

Genetic influences on heart rate variability

PubMed Central

Golosheykin, Simon; Grant, Julia D.; Novak, Olga V.; Heath, Andrew C.; Anokhin, Andrey P.

2016-01-01

Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. PMID:27114045

Structure of the glucagon receptor in complex with a glucagon analogue.

PubMed

Zhang, Haonan; Qiao, Anna; Yang, Linlin; Van Eps, Ned; Frederiksen, Klaus S; Yang, Dehua; Dai, Antao; Cai, Xiaoqing; Zhang, Hui; Yi, Cuiying; Cao, Can; He, Lingli; Yang, Huaiyu; Lau, Jesper; Ernst, Oliver P; Hanson, Michael A; Stevens, Raymond C; Wang, Ming-Wei; Reedtz-Runge, Steffen; Jiang, Hualiang; Zhao, Qiang; Wu, Beili

2018-01-03

Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases. Previous work has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 Å-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR-NNC0640-mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation-which requires conformational changes of the stalk, first extracellular loop and TMD-that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1-PDZ-domain.

PubMed

Sensoy, Ozge; Weinstein, Harel

2015-04-01

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1-PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1-PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ-ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R-GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1-PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1-PDZ-domain

PubMed Central

Sensoy, Ozge; Weinstein, Harel

2015-01-01

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1-PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1-PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ-ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R-GIPC1 complex in sphingolipid/cholesterol membranes shows that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1-PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling. PMID:25592838

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1–PDZ-domain

DOE PAGES

Sensoy, Ozge; Weinstein, Harel

2015-01-12

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of themore » membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Altogether, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling.« less

A watershed model of individual differences in fluid intelligence.

PubMed

Kievit, Rogier A; Davis, Simon W; Griffiths, John; Correia, Marta M; Cam-Can; Henson, Richard N

2016-10-01

Fluid intelligence is a crucial cognitive ability that predicts key life outcomes across the lifespan. Strong empirical links exist between fluid intelligence and processing speed on the one hand, and white matter integrity and processing speed on the other. We propose a watershed model that integrates these three explanatory levels in a principled manner in a single statistical model, with processing speed and white matter figuring as intermediate endophenotypes. We fit this model in a large (N=555) adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) using multiple measures of processing speed, white matter health and fluid intelligence. The model fit the data well, outperforming competing models and providing evidence for a many-to-one mapping between white matter integrity, processing speed and fluid intelligence. The model can be naturally extended to integrate other cognitive domains, endophenotypes and genotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Examining Explanatory Biases in Young Children's Biological Reasoning

ERIC Educational Resources Information Center

Legare, Cristine H.; Gelman, Susan A.

2014-01-01

Despite the well-established literature on explanation in early childhood, little is known about what constrains children's explanations. State change and negative outcomes were examined as potential explanatory biases in the domain of naïve biology, extending upon previous work in the domain of naïve physics. In two studies, preschool children…

Predicting chroma from luma with frequency domain intra prediction

NASA Astrophysics Data System (ADS)

Egge, Nathan E.; Valin, Jean-Marc

2015-03-01

This paper describes a technique for performing intra prediction of the chroma planes based on the reconstructed luma plane in the frequency domain. This prediction exploits the fact that while RGB to YUV color conversion has the property that it decorrelates the color planes globally across an image, there is still some correlation locally at the block level.1 Previous proposals compute a linear model of the spatial relationship between the luma plane (Y) and the two chroma planes (U and V).2 In codecs that use lapped transforms this is not possible since transform support extends across the block boundaries3 and thus neighboring blocks are unavailable during intra- prediction. We design a frequency domain intra predictor for chroma that exploits the same local correlation with lower complexity than the spatial predictor and which works with lapped transforms. We then describe a low- complexity algorithm that directly uses luma coefficients as a chroma predictor based on gain-shape quantization and band partitioning. An experiment is performed that compares these two techniques inside the experimental Daala video codec and shows the lower complexity algorithm to be a better chroma predictor.

Spatial-temporal dynamics of Newtonian and viscoelastic turbulence in channel flow

NASA Astrophysics Data System (ADS)

Wang, Sung-Ning; Shekar, Ashwin; Graham, Michael

2016-11-01

Introducing a trace amount of polymer into liquid turbulent flows can result in substantial reduction of friction drag. This phenomenon has been widely used in fluid transport; however, the mechanism is not well understood. Past studies have found that in minimal domain turbulent simulations, there areoccasional time periods when flow exhibits features such as weaker vortices, lower friction drag and larger log-law slope; these have been denoted as "hibernatingturbulence". Here we address the question of whether similar behavior arises spatio-temporally in extended domains, focusing on turbulence at friction Reynolds numbers near transition and Weissenberg numbers resulting in low-medium drag reduction. By using image analysis and conditional sampling tools, we identify the hibernating states in extended domains and show that they display striking similarity as those in minimal domains. The hibernating states among different Weissenberg numbers exhibit similar flow statistics, suggesting they are unaltered by low to medium viscoelasticity. In addition, the polymer is much less stretched during hibernation. Finally, these hibernating states vanish as Reynolds number increases. However, they reoccur and gradually become dominant with increasing viscoelasticity.

Cognitive reserve is not associated with improved performance in all cognitive domains.

PubMed

Lavrencic, Louise M; Churches, Owen F; Keage, Hannah A D

2017-06-08

Cognitive reserve beneficially affects cognitive performance, even into advanced age. However, the benefits afforded by high cognitive reserve may not extend to all cognitive domains. This study investigated whether cognitive reserve differentially affects performance on cognitive tasks, in 521 cognitively healthy individuals aged 60 to 98 years (Mage = 68, SD = 6.22, 287 female); years of education was used to index cognitive reserve. Cognitive performance variables assessed attention, executive functions, verbal memory, motor performance, orientation, perception of emotion, processing speed, and working memory. Bootstrapped regression analyses revealed that cognitive reserve was associated with attention, executive functions, verbal and working memory, and orientation; and not significantly related to emotion perception, processing speed, or motor performance. Cognitive reserve appears to differentially affect individual cognitive domains, which extends current theory that purports benefits for all domains. This finding highlights the possibility of using tests not (or minimally) associated with cognitive reserve, to screen for cognitive impairment and dementia in late life; these tests will likely best track brain health, free of compensatory neural mechanisms.

Persistence of evolutionary memory: primordial six-transmembrane helical domain mu opiate receptors selectively linked to endogenous morphine signaling.

PubMed

Kream, Richard M; Sheehan, Melinda; Cadet, Patrick; Mantione, Kirk J; Zhu, Wei; Casares, Federico; Stefano, George B

2007-12-01

Biochemical, molecular and pharmacological evidence for two unique six-transmembrane helical (TMH) domain opiate receptors expressed from the micro opioid receptor (MOR) gene have been shown. Designated micro3 and micro4 receptors, both protein species are Class A rhodopsin-like members of the superfamily of G-protein coupled receptors but are selectively tailored to mediate the cellular regulatory effects of endogenous morphine and related morphinan alkaloids via stimulation of nitric oxide (NO) production and release. Both micro3 and micro4 receptors lack an amino acid sequence of approximately 90 amino acids that constitute the extracellular N-terminal and TMH1 domains and part of the first intracellular loop of the micro1 receptor, but retain the empirically defined ligand binding pocket distributed across conserved TMH2, TMH3, and TMH7 domains of the micro1 sequence. Additionally, the receptor proteins are terminated by unique intracellular C-terminal amino acid sequences that serve as putative coupling or docking domains required for constitutive NO synthase activation. Because the recognition profile of micro3 and micro4 receptors is restricted to rigid benzylisoquinoline alkaloids typified by morphine and its extended family of chemical congeners, it is hypothesized that conformational stabilization provided by interaction of extended extracellular N-terminal protein domains and the extracellular loops is required for binding of endogenous opioid peptides as well as synthetic flexible opiate alkaloids.

Maturity model for enterprise interoperability

NASA Astrophysics Data System (ADS)

Guédria, Wided; Naudet, Yannick; Chen, David

2015-01-01

Historically, progress occurs when entities communicate, share information and together create something that no one individually could do alone. Moving beyond people to machines and systems, interoperability is becoming a key factor of success in all domains. In particular, interoperability has become a challenge for enterprises, to exploit market opportunities, to meet their own objectives of cooperation or simply to survive in a growing competitive world where the networked enterprise is becoming a standard. Within this context, many research works have been conducted over the past few years and enterprise interoperability has become an important area of research, ensuring the competitiveness and growth of European enterprises. Among others, enterprises have to control their interoperability strategy and enhance their ability to interoperate. This is the purpose of the interoperability assessment. Assessing interoperability maturity allows a company to know its strengths and weaknesses in terms of interoperability with its current and potential partners, and to prioritise actions for improvement. The objective of this paper is to define a maturity model for enterprise interoperability that takes into account existing maturity models while extending the coverage of the interoperability domain. The assessment methodology is also presented. Both are demonstrated with a real case study.

Computational domain discretization in numerical analysis of flow within granular materials

NASA Astrophysics Data System (ADS)

Sosnowski, Marcin

2018-06-01

The discretization of computational domain is a crucial step in Computational Fluid Dynamics (CFD) because it influences not only the numerical stability of the analysed model but also the agreement of obtained results and real data. Modelling flow in packed beds of granular materials is a very challenging task in terms of discretization due to the existence of narrow spaces between spherical granules contacting tangentially in a single point. Standard approach to this issue results in a low quality mesh and unreliable results in consequence. Therefore the common method is to reduce the diameter of the modelled granules in order to eliminate the single-point contact between the individual granules. The drawback of such method is the adulteration of flow and contact heat resistance among others. Therefore an innovative method is proposed in the paper: single-point contact is extended to a cylinder-shaped volume contact. Such approach eliminates the low quality mesh elements and simultaneously introduces only slight distortion to the flow as well as contact heat transfer. The performed analysis of numerous test cases prove the great potential of the proposed method of meshing the packed beds of granular materials.

A Numerical Model of Unsteady, Subsonic Aeroelastic Behavior. Ph.D Thesis

NASA Technical Reports Server (NTRS)

Strganac, Thomas W.

1987-01-01

A method for predicting unsteady, subsonic aeroelastic responses was developed. The technique accounts for aerodynamic nonlinearities associated with angles of attack, vortex-dominated flow, static deformations, and unsteady behavior. The fluid and the wing together are treated as a single dynamical system, and the equations of motion for the structure and flow field are integrated simultaneously and interactively in the time domain. The method employs an iterative scheme based on a predictor-corrector technique. The aerodynamic loads are computed by the general unsteady vortex-lattice method and are determined simultaneously with the motion of the wing. Because the unsteady vortex-lattice method predicts the wake as part of the solution, the history of the motion is taken into account; hysteresis is predicted. Two models are used to demonstrate the technique: a rigid wing on an elastic support experiencing plunge and pitch about the elastic axis, and an elastic wing rigidly supported at the root chord experiencing spanwise bending and twisting. The method can be readily extended to account for structural nonlinearities and/or substitute aerodynamic load models. The time domain solution coupled with the unsteady vortex-lattice method provides the capability of graphically depicting wing and wake motion.

Socially Extended Cognition and Shared Intentionality

PubMed Central

Lyre, Holger

2018-01-01

The paper looks at the intersection of extended cognition and social cognition. The central claim is that the mechanisms of shared intentionality can equally be considered as coupling mechanisms of cognitive extension into the social domain. This claim will be demonstrated by investigating a detailed example of cooperative action, and it will be argued that such cases imply that socially extended cognition is not only about cognitive vehicles, but that content must additionally be taken into account. It is finally outlined how social content externalism can in principle be grounded in socially extended cognition. PMID:29892254

An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries.

PubMed

Zhu, Zhengqiu; Chen, Bin; Qiu, Sihang; Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

2018-03-27

Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker's parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker's observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants.

An Extended Chemical Plant Environmental Protection Game on Addressing Uncertainties of Human Adversaries

PubMed Central

Wang, Rongxiao; Chen, Feiran; Wang, Yiping; Qiu, Xiaogang

2018-01-01

Chemical production activities in industrial districts pose great threats to the surrounding atmospheric environment and human health. Therefore, developing appropriate and intelligent pollution controlling strategies for the management team to monitor chemical production processes is significantly essential in a chemical industrial district. The literature shows that playing a chemical plant environmental protection (CPEP) game can force the chemical plants to be more compliant with environmental protection authorities and reduce the potential risks of hazardous gas dispersion accidents. However, results of the current literature strictly rely on several perfect assumptions which rarely hold in real-world domains, especially when dealing with human adversaries. To address bounded rationality and limited observability in human cognition, the CPEP game is extended to generate robust schedules of inspection resources for inspection agencies. The present paper is innovative on the following contributions: (i) The CPEP model is extended by taking observation frequency and observation cost of adversaries into account, and thus better reflects the industrial reality; (ii) Uncertainties such as attackers with bounded rationality, attackers with limited observation and incomplete information (i.e., the attacker’s parameters) are integrated into the extended CPEP model; (iii) Learning curve theory is employed to determine the attacker’s observability in the game solver. Results in the case study imply that this work improves the decision-making process for environmental protection authorities in practical fields by bringing more rewards to the inspection agencies and by acquiring more compliance from chemical plants. PMID:29584679

Evaluation of WRF-CHEM Model: A case study of Air Pollution Episode in Istanbul Metropolitan

NASA Astrophysics Data System (ADS)

Aydınöz, Esra; Gürer, Kemal; Toros, Hüseyin

2014-05-01

Istanbul is the largest city in Europe with a population of about 14 million and nearly 3.2 million registered vehicles. Considering that the city is at the junction of major transportation routes on both land and sea, emissions from all motor vehicles operating in the city and those that are in transit is the major source of pollution. The natural gas is used as the major heat source and the impact of other heating sources on the pollution episodes is not clearly known. During 19-29 December 2013 İstanbul metropolitan area experienced a severe PM10 episode with average episode concentration of 127µgm-3 . The episode was associated with a high pressure system with center pressure of 1030 mb residing over Balkans and north of Black Sea and thereby influencing Istanbul. We carried out simulations using the Weather Research and Forecasting model with Chemistry (WRF-CHEM) v3.5 to examine the meteorological conditions and to produce estimates of PM10 over Istanbul for 17-31 December 2013. The three nested domains was setup using 18, 6 and 2 km horizontal grid spacing with (90x90), (115x115) and (130x130) grid points in 1st, 2nd and 3rd domains, respectively. The each domain was run using one way nesting option after preparing the results from the mother domain as an input to subsequent inner domain. 34 vertical levels were used with the lowest layer depth of 15 m above the surface and extending to 15 km at the model top. The model was configured using the model options after many tests to find optimal model parameters and was initialized using global emissions data available publicly. The local emissions database is still in works and is not available to use in the model instead of global data. The estimated PM10 concentrations were compared against the observed conditions. This work shows the first attempt of using WRF-CHEM in Turkey to estimate the pollutant concentrations instead of using other air pollution models such as WRF/CMAQ combination. At the time of constructing this abstract, the model runs were still being conducted and the results will be discussed at the conference. Acknowledgements The authors are grateful to Istanbul Metropolitan Municipality for the air quality data. This study is a background of the online integrated air quality and meteorology modeling project funding by the TUBITAK (Project No: 111Y319) and COST Action ES1004.

Regional Climate Simulations with COSMO-CLM for West Africa using different soil-vegetation-atmosphere-transfer module's (SVAT's)

NASA Astrophysics Data System (ADS)

Breil, Marcus; Panitz, Hans-Jürgen

2013-04-01

Climate predictions on decadal timescales constitute a new field of research, closing the gap between short-term and seasonal weather predictions and long-term climate projections. Therefore, the Federal Ministry of Education and Research in Germany (BMBF) has recently funded the research program MiKlip (Mittelfristige Klimaprognosen), which aims to create a model system that can provide reliable decadal climate forecasts. Recent studies have suggested that one region with high potential decadal predictability is West Africa. Therefore, the DEPARTURE project (DEcadal Prediction of African Rainfall and ATlantic HURricanE Activity) was established within the MiKlip program to assess the feasibility and the potential added value of regional decadal climate predictions for West Africa. To quantify the potential decadal climate predictability, a multi-model approach with the three different regional climate models REMO, WRF and COSMO-CLM (CCLM) will be realized. The presented research will contribute to DEPARTURE by performing hindcast ensemble simulations with CCLM, based on SST-driven global MPI-ESM-LR simulations. Thereby, one focus is on the dynamic soil-vegetation-climate interaction on decadal timescales. Recent studies indicate that there are significant feedbacks between the land-surface and the atmosphere, which might influence the decadal climate variability substantially. To investigate this connection, three different SVAT's (TERRA_ML, Community Land Model (CLM), and VEG3D) will be coupled with the CCLM. Thus, sensitive model parameters shall be identified, whereby the understanding of important processes might be improved. As a first step, the influence of the model domain on the CCLM results was examined. For this purpose, recent CCLM results from simulations for the official CORDEX domain were compared with CCLM results achieved by using an extended DEPARTURE model domain to about 60°W. This sensitivity analysis was performed with a horizontal resolution of 0.44°. Thereby, the analysis showed that the domain size doesn't affect the quality of the simulation results significantly. The impact of different SVAT's on the model performance is supposed to be higher. To investigate this assumption, TERRA_ML, the standard SVAT implemented in CCLM, is replaced by VEG3D using the OASIS3-MCT coupling software. Compared to TERRA_ML, VEG3D includes an explicit vegetation layer, inducing higher correlations with observations as it has been shown in previous studies. The results of both model configurations are analysed and presented for the DEPARTURE model domain.

Development of a new model for short period ocean tidal variations of Earth rotation

NASA Astrophysics Data System (ADS)

Schuh, Harald

2015-08-01

Within project SPOT (Short Period Ocean Tidal variations in Earth rotation) we develop a new high frequency Earth rotation model based on empirical ocean tide models. The main purpose of the SPOT model is its application to space geodetic observations such as GNSS and VLBI.We consider an empirical ocean tide model, which does not require hydrodynamic ocean modeling to determine ocean tidal angular momentum. We use here the EOT11a model of Savcenko & Bosch (2012), which is extended for some additional minor tides (e.g. M1, J1, T2). As empirical tidal models do not provide ocean tidal currents, which are re- quired for the computation of oceanic relative angular momentum, we implement an approach first published by Ray (2001) to estimate ocean tidal current veloci- ties for all tides considered in the extended EOT11a model. The approach itself is tested by application to tidal heights from hydrodynamic ocean tide models, which also provide tidal current velocities. Based on the tidal heights and the associated current velocities the oceanic tidal angular momentum (OTAM) is calculated.For the computation of the related short period variation of Earth rotation, we have re-examined the Euler-Liouville equation for an elastic Earth model with a liquid core. The focus here is on the consistent calculation of the elastic Love num- bers and associated Earth model parameters, which are considered in the Euler- Liouville equation for diurnal and sub-diurnal periods in the frequency domain.

A recipe for simulating the interannual variability of the Asian summer monsoon and its relation with ENSO

NASA Astrophysics Data System (ADS)

Bracco, Annalisa; Kucharski, Fred; Molteni, Franco; Hazeleger, Wilco; Severijns, Camiel

2007-04-01

This study investigates how accurately the interannual variability over the Indian Ocean basin and the relationship between the Indian summer monsoon and the El Niño Southern Oscillation (ENSO) can be simulated by different modelling strategies. With a hierarchy of models, from an atmospherical general circulation model (AGCM) forced by observed SST, to a coupled model with the ocean component limited to the tropical Pacific and Indian Oceans, the role of heat fluxes and of interactive coupling is analyzed. Whenever sea surface temperature anomalies in the Indian basin are created by the coupled model, the inverse relationship between the ENSO index and the Indian summer monsoon rainfall is recovered, and it is preserved if the atmospherical model is forced by the SSTs created by the coupled model. If the ocean model domain is limited to the Indian Ocean, changes in the Walker circulation over the Pacific during El-Niño years induce a decrease of rainfall over the Indian subcontinent. However, the observed correlation between ENSO and the Indian Ocean zonal mode (IOZM) is not properly modelled and the two indices are not significantly correlated, independently on season. Whenever the ocean domain extends to the Pacific, and ENSO can impact both the atmospheric circulation and the ocean subsurface in the equatorial Eastern Indian Ocean, modelled precipitation patterns associated both to ENSO and to the IOZM closely resemble the observations.

A non-local model of fractional heat conduction in rigid bodies

NASA Astrophysics Data System (ADS)

Borino, G.; di Paola, M.; Zingales, M.

2011-03-01

In recent years several applications of fractional differential calculus have been proposed in physics, chemistry as well as in engineering fields. Fractional order integrals and derivatives extend the well-known definitions of integer-order primitives and derivatives of the ordinary differential calculus to real-order operators. Engineering applications of fractional operators spread from viscoelastic models, stochastic dynamics as well as with thermoelasticity. In this latter field one of the main actractives of fractional operators is their capability to interpolate between the heat flux and its time-rate of change, that is related to the well-known second sound effect. In other recent studies a fractional, non-local thermoelastic model has been proposed as a particular case of the non-local, integral, thermoelasticity introduced at the mid of the seventies. In this study the autors aim to introduce a different non-local model of extended irreverible thermodynamics to account for second sound effect. Long-range heat flux is defined and it involves the integral part of the spatial Marchaud fractional derivatives of the temperature field whereas the second-sound effect is accounted for introducing time-derivative of the heat flux in the transport equation. It is shown that the proposed model does not suffer of the pathological problems of non-homogenoeus boundary conditions. Moreover the proposed model coalesces with the Povstenko fractional models in unbounded domains.

Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

DOE PAGES

Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.; ...

2015-03-16

Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.

Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

Impurity distribution and microstructure of Ga-doped ZnO films grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Kvit, A. V.; Yankovich, A. B.; Avrutin, V.; Liu, H.; Izyumskaya, N.; Özgür, Ü.; Morkoç, H.; Voyles, P. M.

2012-12-01

We report microstructural characterization of heavily Ga-doped ZnO (GZO) thin films on GaN and sapphire by aberration-corrected scanning transmission electron microscopy. Growth under oxygen-rich and metal-rich growth conditions leads to changes in the GZO polarity and different extended defects. For GZO layers on sapphire, the primary extended defects are voids, inversion domain boundaries, and low-angle grain boundaries. Ga doping of ZnO grown under metal-rich conditions causes a switch from pure oxygen polarity to mixed oxygen and zinc polarity in small domains. Electron energy loss spectroscopy and energy dispersive spectroscopy spectrum imaging show that Ga is homogeneous, but other residual impurities tend to accumulate at the GZO surface and at extended defects. GZO grown on GaN on c-plane sapphire has Zn polarity and no voids. There are misfit dislocations at the interfaces between GZO and an undoped ZnO buffer layer and at the buffer/GaN interface. Low-angle grain boundaries are the only threading microstructural defects. The potential effects of different extended defects and impurity distributions on free carrier scattering are discussed.

Modeling and analysis of wet friction clutch engagement dynamics

NASA Astrophysics Data System (ADS)

Iqbal, Shoaib; Al-Bender, Farid; Ompusunggu, Agusmian P.; Pluymers, Bert; Desmet, Wim

2015-08-01

In recent years, there has been a significant increase in the usage of wet-friction clutches. Presently researchers across the globe are involved in improving the performance and lifetime of clutches through testing and simulation. To understand the clutch vibrational and dynamical behavior, an SAE#2 test setup mathematical model based on extended reset-integrator friction model is developed in this paper. In order to take into account the different phases of fluid lubrication during engagement cycle, the model includes the experimentally determined Stribeck function. In addition the model considers the viscous effect and the delay in the actuation pressure signal. The model is validated with the experiments performed on the SAE#2 test setup in both time and frequency domains. By analyzing the set of experimental results, we confirmed that the amplitude of shudder vibration is independent of the amplitude of applied contact pressure fluctuation.

MAFIA Version 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiland, T.; Bartsch, M.; Becker, U.

1997-02-01

MAFIA Version 4.0 is an almost completely new version of the general purpose electromagnetic simulator known since 13 years. The major improvements concern the new graphical user interface based on state of the art technology as well as a series of new solvers for new physics problems. MAFIA now covers heat distribution, electro-quasistatics, S-parameters in frequency domain, particle beam tracking in linear accelerators, acoustics and even elastodynamics. The solvers that were available in earlier versions have also been improved and/or extended, as for example the complex eigenmode solver, the 2D--3D coupled PIC solvers. Time domain solvers have new waveguide boundarymore » conditions with an extremely low reflection even near cutoff frequency, concentrated elements are available as well as a variety of signal processing options. Probably the most valuable addition are recursive sub-grid capabilities that enable modeling of very small details in large structures. {copyright} {ital 1997 American Institute of Physics.}« less

MAFIA Version 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiland, T.; Bartsch, M.; Becker, U.

1997-02-01

MAFIA Version 4.0 is an almost completely new version of the general purpose electromagnetic simulator known since 13 years. The major improvements concern the new graphical user interface based on state of the art technology as well as a series of new solvers for new physics problems. MAFIA now covers heat distribution, electro-quasistatics, S-parameters in frequency domain, particle beam tracking in linear accelerators, acoustics and even elastodynamics. The solvers that were available in earlier versions have also been improved and/or extended, as for example the complex eigenmode solver, the 2D-3D coupled PIC solvers. Time domain solvers have new waveguide boundarymore » conditions with an extremely low reflection even near cutoff frequency, concentrated elements are available as well as a variety of signal processing options. Probably the most valuable addition are recursive sub-grid capabilities that enable modeling of very small details in large structures.« less

Motion compensation via redundant-wavelet multihypothesis.

PubMed

Fowler, James E; Cui, Suxia; Wang, Yonghui

2006-10-01

Multihypothesis motion compensation has been widely used in video coding with previous attention focused on techniques employing predictions that are diverse spatially or temporally. In this paper, the multihypothesis concept is extended into the transform domain by using a redundant wavelet transform to produce multiple predictions that are diverse in transform phase. The corresponding multiple-phase inverse transform implicitly combines the phase-diverse predictions into a single spatial-domain prediction for motion compensation. The performance advantage of this redundant-wavelet-multihypothesis approach is investigated analytically, invoking the fact that the multiple-phase inverse involves a projection that significantly reduces the power of a dense-motion residual modeled as additive noise. The analysis shows that redundant-wavelet multihypothesis is capable of up to a 7-dB reduction in prediction-residual variance over an equivalent single-phase, single-hypothesis approach. Experimental results substantiate the performance advantage for a block-based implementation.

Differential and Domain-Specific Associations Among Right-Wing Authoritarianism, Social Dominance Orientation, and Adolescent Delinquency.

PubMed

Oosterhoff, Benjamin; Shook, Natalie J; Clay, Russ; Metzger, Aaron

2017-09-01

Using a dual-process model (DPM) framework, this research examined whether right-wing authoritarianism (RWA) and social dominance orientation (SDO) are differentially associated with adolescent delinquency. In Study 1 ( N = 847; M age = 15.96) and Study 2 ( N = 340; M age = 16.64), adolescents completed measures of RWA, SDO, and engagement in different forms of delinquency. In Study 2, adolescents also reported their beliefs about obeying different laws. Across both studies, adolescents who endorsed greater RWA engaged in lower levels of delinquency and those who endorsed greater SDO engaged in higher levels of delinquency. Findings from Study 2 suggest that these associations are contingent on the domain-specific purpose of the law being violated and are also present with adolescents' beliefs about their obligation to obey laws. These results extend the DPM, demonstrating that RWA and SDO are differentially linked with youth delinquency.

Dynamics and morphology of chiral magnetic bubbles in perpendicularly magnetized ultra-thin films

NASA Astrophysics Data System (ADS)

Sarma, Bhaskarjyoti; Garcia-Sanchez, Felipe; Nasseri, S. Ali; Casiraghi, Arianna; Durin, Gianfranco

2018-06-01

We study bubble domain wall dynamics using micromagnetic simulations in perpendicularly magnetized ultra-thin films with disorder and Dzyaloshinskii-Moriya interaction. Disorder is incorporated into the material as grains with randomly distributed sizes and varying exchange constant at the edges. As expected, magnetic bubbles expand asymmetrically along the axis of the in-plane field under the simultaneous application of out-of-plane and in-plane fields. Remarkably, the shape of the bubble has a ripple-like part which causes a kink-like (steep decrease) feature in the velocity versus in-plane field curve. We show that these ripples originate due to the nucleation and interaction of vertical Bloch lines. Furthermore, we show that the Dzyaloshinskii-Moriya interaction field is not constant but rather depends on the in-plane field. We also extend the collective coordinate model for domain wall motion to a magnetic bubble and compare it with the results of micromagnetic simulations.

Analytic solutions to modelling exponential and harmonic functions using Chebyshev polynomials: fitting frequency-domain lifetime images with photobleaching.

PubMed

Malachowski, George C; Clegg, Robert M; Redford, Glen I

2007-12-01

A novel approach is introduced for modelling linear dynamic systems composed of exponentials and harmonics. The method improves the speed of current numerical techniques up to 1000-fold for problems that have solutions of multiple exponentials plus harmonics and decaying components. Such signals are common in fluorescence microscopy experiments. Selective constraints of the parameters being fitted are allowed. This method, using discrete Chebyshev transforms, will correctly fit large volumes of data using a noniterative, single-pass routine that is fast enough to analyse images in real time. The method is applied to fluorescence lifetime imaging data in the frequency domain with varying degrees of photobleaching over the time of total data acquisition. The accuracy of the Chebyshev method is compared to a simple rapid discrete Fourier transform (equivalent to least-squares fitting) that does not take the photobleaching into account. The method can be extended to other linear systems composed of different functions. Simulations are performed and applications are described showing the utility of the method, in particular in the area of fluorescence microscopy.

Cognitive Abilities, Social Adaptation, and Externalizing Behavior Problems in Childhood and Adolescence: Specific Cascade Effects Across Development.

PubMed

Racz, Sarah Jensen; Putnick, Diane L; Suwalsky, Joan T D; Hendricks, Charlene; Bornstein, Marc H

2017-08-01

Children's and adolescents' cognitive abilities, social adaptation, and externalizing behaviors are broadly associated with each other at the bivariate level; however, the direction, ordering, and uniqueness of these associations have yet to be identified. Developmental cascade models are particularly well-suited to (1) discern unique pathways among psychological domains and (2) model stability in and covariation among constructs, allowing for conservative tests of longitudinal associations. The current study aimed to identify specific cascade effects among children's cognitive abilities, social adaptation, and externalizing behaviors, beginning in preschool and extending through adolescence. Children (46.2 % female) and mothers (N = 351 families) provided data when children were 4, 10, and 14 years old. Cascade effects highlighted significant stability in these domains. Unique longitudinal associations were identified between (1) age-10 cognitive abilities and age-14 social adaptation, (2) age-4 social adaptation and age-10 externalizing behavior, and (3) age-10 externalizing behavior and age-14 social adaptation. These findings suggest that children's social adaptation in preschool and externalizing behavior in middle childhood may be ideal intervention targets to enhance adolescent well-being.

Extending XNAT Platform with an Incremental Semantic Framework

PubMed Central

Timón, Santiago; Rincón, Mariano; Martínez-Tomás, Rafael

2017-01-01

Informatics increases the yield from neuroscience due to improved data. Data sharing and accessibility enable joint efforts between different research groups, as well as replication studies, pivotal for progress in the field. Research data archiving solutions are evolving rapidly to address these necessities, however, distributed data integration is still difficult because of the need of explicit agreements for disparate data models. To address these problems, ontologies are widely used in biomedical research to obtain common vocabularies and logical descriptions, but its application may suffer from scalability issues, domain bias, and loss of low-level data access. With the aim of improving the application of semantic models in biobanking systems, an incremental semantic framework that takes advantage of the latest advances in biomedical ontologies and the XNAT platform is designed and implemented. We follow a layered architecture that allows the alignment of multi-domain biomedical ontologies to manage data at different levels of abstraction. To illustrate this approach, the development is integrated in the JPND (EU Joint Program for Neurodegenerative Disease) APGeM project, focused on finding early biomarkers for Alzheimer's and other dementia related diseases. PMID:28912709

Extending XNAT Platform with an Incremental Semantic Framework.

PubMed

Timón, Santiago; Rincón, Mariano; Martínez-Tomás, Rafael

2017-01-01

Informatics increases the yield from neuroscience due to improved data. Data sharing and accessibility enable joint efforts between different research groups, as well as replication studies, pivotal for progress in the field. Research data archiving solutions are evolving rapidly to address these necessities, however, distributed data integration is still difficult because of the need of explicit agreements for disparate data models. To address these problems, ontologies are widely used in biomedical research to obtain common vocabularies and logical descriptions, but its application may suffer from scalability issues, domain bias, and loss of low-level data access. With the aim of improving the application of semantic models in biobanking systems, an incremental semantic framework that takes advantage of the latest advances in biomedical ontologies and the XNAT platform is designed and implemented. We follow a layered architecture that allows the alignment of multi-domain biomedical ontologies to manage data at different levels of abstraction. To illustrate this approach, the development is integrated in the JPND (EU Joint Program for Neurodegenerative Disease) APGeM project, focused on finding early biomarkers for Alzheimer's and other dementia related diseases.

Fluid Structure Interaction simulation of heart prosthesis in patient-specific left-ventricle/aorta anatomies

NASA Astrophysics Data System (ADS)

Le, Trung; Borazjani, Iman; Sotiropoulos, Fotis

2009-11-01

In order to test and optimize heart valve prosthesis and enable virtual implantation of other biomedical devices it is essential to develop and validate high-resolution FSI-CFD codes for carrying out simulations in patient-specific geometries. We have developed a powerful numerical methodology for carrying out FSI simulations of cardiovascular flows based on the CURVIB approach (Borazjani, L. Ge, and F. Sotiropoulos, Journal of Computational physics, vol. 227, pp. 7587-7620 2008). We have extended our FSI method to overset grids to handle efficiently more complicated geometries e.g. simulating an MHV implanted in an anatomically realistic aorta and left-ventricle. A compliant, anatomic left-ventricle is modeled using prescribed motion in one domain. The mechanical heart valve is placed inside the second domain i.e. the body-fitted curvilinear mesh of the anatomic aorta. The simulations of an MHV with a left-ventricle model underscore the importance of inflow conditions and ventricular compliance for such simulations and demonstrate the potential of our method as a powerful tool for patient-specific simulations.

Stochastic population dynamics in spatially extended predator-prey systems

NASA Astrophysics Data System (ADS)

Dobramysl, Ulrich; Mobilia, Mauro; Pleimling, Michel; Täuber, Uwe C.

2018-02-01

Spatially extended population dynamics models that incorporate demographic noise serve as case studies for the crucial role of fluctuations and correlations in biological systems. Numerical and analytic tools from non-equilibrium statistical physics capture the stochastic kinetics of these complex interacting many-particle systems beyond rate equation approximations. Including spatial structure and stochastic noise in models for predator-prey competition invalidates the neutral Lotka-Volterra population cycles. Stochastic models yield long-lived erratic oscillations stemming from a resonant amplification mechanism. Spatially extended predator-prey systems display noise-stabilized activity fronts that generate persistent correlations. Fluctuation-induced renormalizations of the oscillation parameters can be analyzed perturbatively via a Doi-Peliti field theory mapping of the master equation; related tools allow detailed characterization of extinction pathways. The critical steady-state and non-equilibrium relaxation dynamics at the predator extinction threshold are governed by the directed percolation universality class. Spatial predation rate variability results in more localized clusters, enhancing both competing species’ population densities. Affixing variable interaction rates to individual particles and allowing for trait inheritance subject to mutations induces fast evolutionary dynamics for the rate distributions. Stochastic spatial variants of three-species competition with ‘rock-paper-scissors’ interactions metaphorically describe cyclic dominance. These models illustrate intimate connections between population dynamics and evolutionary game theory, underscore the role of fluctuations to drive populations toward extinction, and demonstrate how space can support species diversity. Two-dimensional cyclic three-species May-Leonard models are characterized by the emergence of spiraling patterns whose properties are elucidated by a mapping onto a complex Ginzburg-Landau equation. Multiple-species extensions to general ‘food networks’ can be classified on the mean-field level, providing both fundamental understanding of ensuing cooperativity and profound insight into the rich spatio-temporal features and coarsening kinetics in the corresponding spatially extended systems. Novel space-time patterns emerge as a result of the formation of competing alliances; e.g. coarsening domains that each incorporate rock-paper-scissors competition games.

Input design for identification of aircraft stability and control derivatives

NASA Technical Reports Server (NTRS)

Gupta, N. K.; Hall, W. E., Jr.

1975-01-01

An approach for designing inputs to identify stability and control derivatives from flight test data is presented. This approach is based on finding inputs which provide the maximum possible accuracy of derivative estimates. Two techniques of input specification are implemented for this objective - a time domain technique and a frequency domain technique. The time domain technique gives the control input time history and can be used for any allowable duration of test maneuver, including those where data lengths can only be of short duration. The frequency domain technique specifies the input frequency spectrum, and is best applied for tests where extended data lengths, much longer than the time constants of the modes of interest, are possible. These technqiues are used to design inputs to identify parameters in longitudinal and lateral linear models of conventional aircraft. The constraints of aircraft response limits, such as on structural loads, are realized indirectly through a total energy constraint on the input. Tests with simulated data and theoretical predictions show that the new approaches give input signals which can provide more accurate parameter estimates than can conventional inputs of the same total energy. Results obtained indicate that the approach has been brought to the point where it should be used on flight tests for further evaluation.

Preliminary frequency-domain analysis for the reconstructed spatial resolution of muon tomography

NASA Astrophysics Data System (ADS)

Yu, B.; Zhao, Z.; Wang, X.; Wang, Y.; Wu, D.; Zeng, Z.; Zeng, M.; Yi, H.; Luo, Z.; Yue, X.; Cheng, J.

2014-11-01

Muon tomography is an advanced technology to non-destructively detect high atomic number materials. It exploits the multiple Coulomb scattering information of muon to reconstruct the scattering density image of the traversed object. Because of the statistics of muon scattering, the measurement error of system and the data incompleteness, the reconstruction is always accompanied with a certain level of interference, which will influence the reconstructed spatial resolution. While statistical noises can be reduced by extending the measuring time, system parameters determine the ultimate spatial resolution that one system can reach. In this paper, an effective frequency-domain model is proposed to analyze the reconstructed spatial resolution of muon tomography. The proposed method modifies the resolution analysis in conventional computed tomography (CT) to fit the different imaging mechanism in muon scattering tomography. The measured scattering information is described in frequency domain, then a relationship between the measurements and the original image is proposed in Fourier domain, which is named as "Muon Central Slice Theorem". Furthermore, a preliminary analytical expression of the ultimate reconstructed spatial is derived, and the simulations are performed for validation. While the method is able to predict the ultimate spatial resolution of a given system, it can also be utilized for the optimization of system design and construction.

Stimulated luminescence emission from localized recombination in randomly distributed defects.

PubMed

Jain, Mayank; Guralnik, Benny; Andersen, Martin Thalbitzer

2012-09-26

We present a new kinetic model describing localized electronic recombination through the excited state of the donor (d) to an acceptor (a) centre in luminescent materials. In contrast to the existing models based on the localized transition model (LTM) of Halperin and Braner (1960 Phys. Rev. 117 408-15) which assumes a fixed d → a tunnelling probability for the entire crystal, our model is based on nearest-neighbour recombination within randomly distributed centres. Such a random distribution can occur through the entire volume or within the defect complexes of the dosimeter, and implies that the tunnelling probability varies with the donor-acceptor (d-a) separation distance. We first develop an 'exact kinetic model' that incorporates this variation in tunnelling probabilities, and evolves both in spatial as well as temporal domains. We then develop a simplified one-dimensional, semi-analytical model that evolves only in the temporal domain. An excellent agreement is observed between thermally and optically stimulated luminescence (TL and OSL) results produced from the two models. In comparison to the first-order kinetic behaviour of the LTM of Halperin and Braner (1960 Phys. Rev. 117 408-15), our model results in a highly asymmetric TL peak; this peak can be understood to derive from a continuum of several first-order TL peaks. Our model also shows an extended power law behaviour for OSL (or prompt luminescence), which is expected from localized recombination mechanisms in materials with random distribution of centres.

High-resolution modeling assessment of tidal stream resource in Western Passage of Maine, USA

NASA Astrophysics Data System (ADS)

Yang, Zhaoqing; Wang, Taiping; Feng, Xi; Xue, Huijie; Kilcher, Levi

2017-04-01

Although significant efforts have been taken to assess the maximum potential of tidal stream energy at system-wide scale, accurate assessment of tidal stream energy resource at project design scale requires detailed hydrodynamic simulations using high-resolution three-dimensional (3-D) numerical models. Extended model validation against high quality measured data is essential to minimize the uncertainties of the resource assessment. Western Passage in the State of Maine in U.S. has been identified as one of the top ranking sites for tidal stream energy development in U.S. coastal waters, based on a number of criteria including tidal power density, market value and transmission distance. This study presents an on-going modeling effort for simulating the tidal hydrodynamics in Western Passage using the 3-D unstructured-grid Finite Volume Community Ocean Model (FVCOM). The model domain covers a large region including the entire the Bay of Fundy with grid resolution varies from 20 m in the Western Passage to approximately 1000 m along the open boundary near the mouth of Bay of Fundy. Preliminary model validation was conducted using existing NOAA measurements within the model domain. Spatial distributions of tidal power density were calculated and extractable tidal energy was estimated using a tidal turbine module embedded in FVCOM under different tidal farm scenarios. Additional field measurements to characterize resource and support model validation were discussed. This study provides an example of high resolution resource assessment based on the guidance recommended by the International Electrotechnical Commission Technical Specification.

MHD Simulations of Plasma Dynamics with Non-Axisymmetric Boundaries

NASA Astrophysics Data System (ADS)

Hansen, Chris; Levesque, Jeffrey; Morgan, Kyle; Jarboe, Thomas

2015-11-01

The arbitrary geometry, 3D extended MHD code PSI-TET is applied to linear and non-linear simulations of MCF plasmas with non-axisymmetric boundaries. Progress and results from simulations on two experiments will be presented: 1) Detailed validation studies of the HIT-SI experiment with self-consistent modeling of plasma dynamics in the helicity injectors. Results will be compared to experimental data and NIMROD simulations that model the effect of the helicity injectors through boundary conditions on an axisymmetric domain. 2) Linear studies of HBT-EP with different wall configurations focusing on toroidal asymmetries in the adjustable conducting wall. HBT-EP studies the effect of active/passive stabilization with an adjustable ferritic wall. Results from linear verification and benchmark studies of ideal mode growth with and without toroidal asymmetries will be presented and compared to DCON predictions. Simulations of detailed experimental geometries are enabled by use of the PSI-TET code, which employs a high order finite element method on unstructured tetrahedral grids that are generated directly from CAD models. Further development of PSI-TET will also be presented including work to support resistive wall regions within extended MHD simulations. Work supported by DoE.

Performance Enhancement of Pharmacokinetic Diffuse Fluorescence Tomography by Use of Adaptive Extended Kalman Filtering.

PubMed

Wang, Xin; Wu, Linhui; Yi, Xi; Zhang, Yanqi; Zhang, Limin; Zhao, Huijuan; Gao, Feng

2015-01-01

Due to both the physiological and morphological differences in the vascularization between healthy and diseased tissues, pharmacokinetic diffuse fluorescence tomography (DFT) can provide contrast-enhanced and comprehensive information for tumor diagnosis and staging. In this regime, the extended Kalman filtering (EKF) based method shows numerous advantages including accurate modeling, online estimation of multiparameters, and universal applicability to any optical fluorophore. Nevertheless the performance of the conventional EKF highly hinges on the exact and inaccessible prior knowledge about the initial values. To address the above issues, an adaptive-EKF scheme is proposed based on a two-compartmental model for the enhancement, which utilizes a variable forgetting-factor to compensate the inaccuracy of the initial states and emphasize the effect of the current data. It is demonstrated using two-dimensional simulative investigations on a circular domain that the proposed adaptive-EKF can obtain preferable estimation of the pharmacokinetic-rates to the conventional-EKF and the enhanced-EKF in terms of quantitativeness, noise robustness, and initialization independence. Further three-dimensional numerical experiments on a digital mouse model validate the efficacy of the method as applied in realistic biological systems.

Modelling Biogeochemistry Across Domains with The Modular System for Shelves and Coasts (MOSSCO)

NASA Astrophysics Data System (ADS)

Burchard, H.; Lemmen, C.; Hofmeister, R.; Knut, K.; Nasermoaddeli, M. H.; Kerimoglu, O.; Koesters, F.; Wirtz, K.

2016-02-01

Coastal biogeochemical processes extend from the atmosphere through the water column and the epibenthos into the ocean floor, laterally they are determined by freshwater inflows and open water exchange, and in situ they are mediated by physical, chemical and biological interactions. We use the new Modular System for Shelves and Coasts (MOSSCO, http://www.mossco.de) to obtain an integrated view of coastal biogeochemistry. MOSSCO is a coupling framework that builds on existing coupling technologies like the Earth System Modeling Framework (ESMF, for domain-coupling) and the Framework for Aquatic Biogeochemistry (FABM, for process coupling). MOSSCO facilitates the communication about and the integration of existing and of new process models into a threedimensional regional coastal modelling context. In the MOSSCO concept, the integrating framework imposes very few restrictions on contributed data or models; in fact, there is no distinction made between data and models. The few requirements are: (1) principle coupleability, i.e. access to I/O and timing information in submodels, which has recently been referred to as the Basic Model Interface (BMI) (2) open source/open data access and licencing and (3) communication of metadata, such as spatiotemporal information, naming conventions, and physical units. These requirements suffice to integrate different models and data sets into the MOSSCO infrastructure and subsequently built a modular integrated modeling tool that can span a diversity of processes and domains. Here, we demonstrate a MOSSCO application for the southern North Sea, where atmospheric deposition, biochemical processing in the water column and the ocean floor, lateral nutrient replenishment, and wave- and current-dependent remobilization from sediments are accounted for by modular components. A multi-annual simulation yields realistic succession of the spatial gradients of dissolved nutrients, of chlorophyll variability and gross primary production rates and of benthic denitrification rates for this intriguing coastal system.

Impact of Expectancy-Value and Situational Interest Motivation Specificity on Physical Education Outcomes

ERIC Educational Resources Information Center

Ding, Haiyong; Sun, Haichun; Chen, Ang

2013-01-01

To be successful in learning, students need to be motivated to engage and learn. The domain-specificity motivation theory articulates that student motivation is often determined by the content being taught to them. The purpose of this study was to extend the theory by determining domain-specificity of situational interest and expectancy-value…

The Degrees of Freedom Concept--Extending the Domain

ERIC Educational Resources Information Center

Biernacki, J. J.

2016-01-01

The degrees of freedom (DOF) concept is a powerful tool that has been taught since at least the '70s in undergraduate curriculum, typically introduced in the context of a first course on material and energy balances. The concept, however, has not been widely applied beyond the material balance domain and in general is not taught as a unified…

Recovering the Role of Reasoning in Moral Education to Address Inequity and Social Justice

ERIC Educational Resources Information Center

Nucci, Larry

2016-01-01

This article reasserts the centrality of reasoning as the focus for moral education. Attention to moral cognition must be extended to incorporate sociogenetic processes in moral growth. Moral education is not simply growth within the moral domain, but addresses capacities of students to engage in cross-domain coordination. Development beyond…

Local spectrum analysis of field propagation in an anisotropic medium. Part II. Time-dependent fields.

PubMed

Tinkelman, Igor; Melamed, Timor

2005-06-01

In Part I of this two-part investigation [J. Opt. Soc. Am. A 22, 1200 (2005)], we presented a theory for phase-space propagation of time-harmonic electromagnetic fields in an anisotropic medium characterized by a generic wave-number profile. In this Part II, these investigations are extended to transient fields, setting a general analytical framework for local analysis and modeling of radiation from time-dependent extended-source distributions. In this formulation the field is expressed as a superposition of pulsed-beam propagators that emanate from all space-time points in the source domain and in all directions. Using time-dependent quadratic-Lorentzian windows, we represent the field by a phase-space spectral distribution in which the propagating elements are pulsed beams, which are formulated by a transient plane-wave spectrum over the extended-source plane. By applying saddle-point asymptotics, we extract the beam phenomenology in the anisotropic environment resulting from short-pulsed processing. Finally, the general results are applied to the special case of uniaxial crystal and compared with a reference solution.

Micromorphic approach for gradient-extended thermo-elastic-plastic solids in the logarithmic strain space

NASA Astrophysics Data System (ADS)

Aldakheel, Fadi

2017-11-01

The coupled thermo-mechanical strain gradient plasticity theory that accounts for microstructure-based size effects is outlined within this work. It extends the recent work of Miehe et al. (Comput Methods Appl Mech Eng 268:704-734, 2014) to account for thermal effects at finite strains. From the computational viewpoint, the finite element design of the coupled problem is not straightforward and requires additional strategies due to the difficulties near the elastic-plastic boundaries. To simplify the finite element formulation, we extend it toward the micromorphic approach to gradient thermo-plasticity model in the logarithmic strain space. The key point is the introduction of dual local-global field variables via a penalty method, where only the global fields are restricted by boundary conditions. Hence, the problem of restricting the gradient variable to the plastic domain is relaxed, which makes the formulation very attractive for finite element implementation as discussed in Forest (J Eng Mech 135:117-131, 2009) and Miehe et al. (Philos Trans R Soc A Math Phys Eng Sci 374:20150170, 2016).

Integrating natural language processing and web GIS for interactive knowledge domain visualization

NASA Astrophysics Data System (ADS)

Du, Fangming

Recent years have seen a powerful shift towards data-rich environments throughout society. This has extended to a change in how the artifacts and products of scientific knowledge production can be analyzed and understood. Bottom-up approaches are on the rise that combine access to huge amounts of academic publications with advanced computer graphics and data processing tools, including natural language processing. Knowledge domain visualization is one of those multi-technology approaches, with its aim of turning domain-specific human knowledge into highly visual representations in order to better understand the structure and evolution of domain knowledge. For example, network visualizations built from co-author relations contained in academic publications can provide insight on how scholars collaborate with each other in one or multiple domains, and visualizations built from the text content of articles can help us understand the topical structure of knowledge domains. These knowledge domain visualizations need to support interactive viewing and exploration by users. Such spatialization efforts are increasingly looking to geography and GIS as a source of metaphors and practical technology solutions, even when non-georeferenced information is managed, analyzed, and visualized. When it comes to deploying spatialized representations online, web mapping and web GIS can provide practical technology solutions for interactive viewing of knowledge domain visualizations, from panning and zooming to the overlay of additional information. This thesis presents a novel combination of advanced natural language processing - in the form of topic modeling - with dimensionality reduction through self-organizing maps and the deployment of web mapping/GIS technology towards intuitive, GIS-like, exploration of a knowledge domain visualization. A complete workflow is proposed and implemented that processes any corpus of input text documents into a map form and leverages a web application framework to let users explore knowledge domain maps interactively. This workflow is implemented and demonstrated for a data set of more than 66,000 conference abstracts.

Evolution of the Antarctic polar vortex in spring: Response of a GCM to a prescribed Antarctic ozone hole

NASA Technical Reports Server (NTRS)

Boville, B. A.; Kiehl, J. T.; Briegleb, B. P.

1988-01-01

The possible effect of the Antartic ozone hole on the evolution of the polar vortex during late winter and spring using a general circulation model (GCM) is examined. The GCM is a version of the NCAR Community Climate Model whose domain extends from the surface to the mesosphere and is similar to that described on Boville and Randel (1986). Ozone is not a predicted variable in the model. A zonally averaged ozone distribution is specified as a function of latitude, pressure and month for the radiation parameterization. Rather that explicitly address reasons for the formation of the ozone hole, researchers postulate its existence and ask what effect it has on the subsequent evolution of the vortex. The evolution of the model when an ozone hole is imposed is then discussed.

Post-earthquake relaxation evidence for laterally variable viscoelastic structure and elevated water concentration in the southwestern California mantle

NASA Astrophysics Data System (ADS)

Pollitz, F. F.

2014-12-01

I re-examine the lower crust and mantle relaxation following two large events in the Mojave Desert: the 1992 M7.3 Landers and 1999 M7.1 Hector Mine, California, earthquakes. More than a decade of GPS time series from regional sites out to 250 km from the ruptures are used to constrain models of postseismic relaxation. Crustal motions in the Mojave Desert region are elevated for several years following each event, with perturbations from a pre-Landers background of order mm to cm per year. I consider afterslip and relaxation of the ductile lower crust and mantle to explain these motions. To account for broad scale relaxation, the Burgers body model is employed, involving Kelvin (transient) viscosity and rigidity and Maxwell (steady state) viscosity and rigidity. I use the code VISCO2.5D to perform 2.5D modeling of the postseismic relaxation (3D quasi-static motions computed on 2D, laterally heterogeneous viscoelastic structures; Pollitz, 2014 GJI). Joint afterslip / postseismic relaxation modeling of continuous GPS time series up to 10.46 years following the Hector Mine earthquake (i.e. up to the time of the 2010 M7.2 El Mayor-Cucapah earthquake) reveals that a northwest-trending `southwest domain' that envelopes the San Andreas fault system and western Mojave Desert has ~4 times larger Maxwell mantle viscosity than the adjacent `northeast domain' that extends inland and envelopes the Landers and Hector Mine rupture areas in the central Mojave Desert. This pattern is counter to that expected from regional heat flow, which is higher in the northeast domain, but it is explicable by means of a non-linear rheology that includes dependence on both strain rate and water concentration. I infer that the southwest domain mantle has a relatively low steady-state viscosity because of its high strain rate and water content. The relatively low mantle water content of the northeast domain is interpreted to result from the continual extraction of water through igneous and volcanic activity over the past ~20 Myr. The inference of Maxwellian viscosities is possible because the material relaxation times involved (5 years and 20 years for the SW and NE domains, respectively) are to a large extent spanned by the decade of available post-Hector Mine observations.

Predictive Modeling of Risk Associated with Temperature Extremes over Continental US

NASA Astrophysics Data System (ADS)

Kravtsov, S.; Roebber, P.; Brazauskas, V.

2016-12-01

We build an extremely statistically accurate, essentially bias-free empirical emulator of atmospheric surface temperature and apply it for meteorological risk assessment over the domain of continental US. The resulting prediction scheme achieves an order-of-magnitude or larger gain of numerical efficiency compared with the schemes based on high-resolution dynamical atmospheric models, leading to unprecedented accuracy of the estimated risk distributions. The empirical model construction methodology is based on our earlier work, but is further modified to account for the influence of large-scale, global climate change on regional US weather and climate. The resulting estimates of the time-dependent, spatially extended probability of temperature extremes over the simulation period can be used as a risk management tool by insurance companies and regulatory governmental agencies.

What else are psychotherapy trainees learning? A qualitative model of students' personal experiences based on two populations.

PubMed

Pascual-Leone, Antonio; Rodriguez-Rubio, Beatriz; Metler, Samantha

2013-01-01

After an introductory course in experiential-integrative psychotherapy, 21 graduate students provided personal narratives of their experiences, which were analyzed using the grounded theory method. Results produced 37 hierarchically organized experiences, revealing that students perceived multiple changes in both professional (i.e., skill acquisition and learning related to the therapeutic process) and personal (i.e., self growth in a more private sphere) domains. Analysis also highlighted key areas of difficulties in training. By adding the personal accounts of graduate trainees, this study enriches and extends Pascual-Leone et al.'s (2012) findings on undergraduates' experiences, raising the number of cases represented in the model to 45. Findings confirm the model of novice trainee experiences while highlighting the unique experiences of undergraduate vs. graduate trainees.

Biomedical hypothesis generation by text mining and gene prioritization.

PubMed

Petric, Ingrid; Ligeti, Balazs; Gyorffy, Balazs; Pongor, Sandor

2014-01-01

Text mining methods can facilitate the generation of biomedical hypotheses by suggesting novel associations between diseases and genes. Previously, we developed a rare-term model called RaJoLink (Petric et al, J. Biomed. Inform. 42(2): 219-227, 2009) in which hypotheses are formulated on the basis of terms rarely associated with a target domain. Since many current medical hypotheses are formulated in terms of molecular entities and molecular mechanisms, here we extend the methodology to proteins and genes, using a standardized vocabulary as well as a gene/protein network model. The proposed enhanced RaJoLink rare-term model combines text mining and gene prioritization approaches. Its utility is illustrated by finding known as well as potential gene-disease associations in ovarian cancer using MEDLINE abstracts and the STRING database.

The extended TRIP supporting VoIP routing reservation with distributed QoS

NASA Astrophysics Data System (ADS)

Wang, Furong; Wu, Ye

2004-04-01

In this paper, an existing protocol, i.e. TRIP (Telephony Routing over IP) is developed to provide distributed QoS when making resource reservations for VoIP services such as H.323, SIP. Enhanced LSs (location servers) are deployed in ITADs (IP Telephony Administrative Domains) to take in charge of intra-domain routing policy because of small propagation price. It is an easy way to find an IP telephone route for intra-domain VoIP media association and simultaneously possess intra-domain load balancing features. For those routing reservations bridging domains, inter-domain routing policy is responsible for finding the shortest inter-domain route with enough resources. I propose the routing preference policy based on QoS price when the session traffic is shaped by a token bucket, related QoS messages, and message cooperation.

Magnetically Defined Qubits on 3D Topological Insulators

NASA Astrophysics Data System (ADS)

Ferreira, Gerson J.; Loss, Daniel

2014-03-01

We explore potentials that break time-reversal symmetry to confine the surface states of 3D topological insulators into quantum wires and quantum dots. A magnetic domain wall on a ferromagnet insulator cap layer provides interfacial states predicted to show the quantum anomalous Hall effect. Here, we show that confinement can also occur at magnetic domain heterostructures, with states extended in the inner domain, as well as interfacial QAHE states at the surrounding domain walls. The proposed geometry allows the isolation of the wire and dot from spurious circumventing surface states. For the quantum dots, we find that highly spin-polarized quantized QAHE states at the dot edge constitute a promising candidate for quantum computing qubits. See [Ferreira and Loss, Phys. Rev. Lett. 111, 106802 (2013)]. We explore potentials that break time-reversal symmetry to confine the surface states of 3D topological insulators into quantum wires and quantum dots. A magnetic domain wall on a ferromagnet insulator cap layer provides interfacial states predicted to show the quantum anomalous Hall effect. Here, we show that confinement can also occur at magnetic domain heterostructures, with states extended in the inner domain, as well as interfacial QAHE states at the surrounding domain walls. The proposed geometry allows the isolation of the wire and dot from spurious circumventing surface states. For the quantum dots, we find that highly spin-polarized quantized QAHE states at the dot edge constitute a promising candidate for quantum computing qubits. See [Ferreira and Loss, Phys. Rev. Lett. 111, 106802 (2013)]. We acknowledge support from the Swiss NSF, NCCR Nanoscience, NCCR QSIT, and the Brazillian Research Support Center Initiative (NAP Q-NANO) from Pró-Reitoria de Pesquisa (PRP/USP).

Unstructured grid modelling of offshore wind farm impacts on seasonally stratified shelf seas

NASA Astrophysics Data System (ADS)

Cazenave, Pierre William; Torres, Ricardo; Allen, J. Icarus

2016-06-01

Shelf seas comprise approximately 7% of the world's oceans and host enormous economic activity. Development of energy installations (e.g. Offshore Wind Farms (OWFs), tidal turbines) in response to increased demand for renewable energy requires a careful analysis of potential impacts. Recent remote sensing observations have identified kilometre-scale impacts from OWFs. Existing modelling evaluating monopile impacts has fallen into two camps: small-scale models with individually resolved turbines looking at local effects; and large-scale analyses but with sub-grid scale turbine parameterisations. This work straddles both scales through a 3D unstructured grid model (FVCOM): wind turbine monopiles in the eastern Irish Sea are explicitly described in the grid whilst the overall grid domain covers the south-western UK shelf. Localised regions of decreased velocity extend up to 250 times the monopile diameter away from the monopile. Shelf-wide, the amplitude of the M2 tidal constituent increases by up to 7%. The turbines enhance localised vertical mixing which decreases seasonal stratification. The spatial extent of this extends well beyond the turbines into the surrounding seas. With significant expansion of OWFs on continental shelves, this work highlights the importance of how OWFs may impact coastal (e.g. increased flooding risk) and offshore (e.g. stratification and nutrient cycling) areas.

High and low frequency unfolded partial least squares regression based on empirical mode decomposition for quantitative analysis of fuel oil samples.

PubMed

Bian, Xihui; Li, Shujuan; Lin, Ligang; Tan, Xiaoyao; Fan, Qingjie; Li, Ming

2016-06-21

Accurate prediction of the model is fundamental to the successful analysis of complex samples. To utilize abundant information embedded over frequency and time domains, a novel regression model is presented for quantitative analysis of hydrocarbon contents in the fuel oil samples. The proposed method named as high and low frequency unfolded PLSR (HLUPLSR), which integrates empirical mode decomposition (EMD) and unfolded strategy with partial least squares regression (PLSR). In the proposed method, the original signals are firstly decomposed into a finite number of intrinsic mode functions (IMFs) and a residue by EMD. Secondly, the former high frequency IMFs are summed as a high frequency matrix and the latter IMFs and residue are summed as a low frequency matrix. Finally, the two matrices are unfolded to an extended matrix in variable dimension, and then the PLSR model is built between the extended matrix and the target values. Coupled with Ultraviolet (UV) spectroscopy, HLUPLSR has been applied to determine hydrocarbon contents of light gas oil and diesel fuels samples. Comparing with single PLSR and other signal processing techniques, the proposed method shows superiority in prediction ability and better model interpretation. Therefore, HLUPLSR method provides a promising tool for quantitative analysis of complex samples. Copyright © 2016 Elsevier B.V. All rights reserved.

RF wave simulation for cold edge plasmas using the MFEM library

NASA Astrophysics Data System (ADS)

Shiraiwa, S.; Wright, J. C.; Bonoli, P. T.; Kolev, T.; Stowell, M.

2017-10-01

A newly developed generic electro-magnetic (EM) simulation tool for modeling RF wave propagation in SOL plasmas is presented. The primary motivation of this development is to extend the domain partitioning approach for incorporating arbitrarily shaped SOL plasmas and antenna to the TORIC core ICRF solver, which was previously demonstrated in the 2D geometry [S. Shiraiwa, et. al., "HISTORIC: extending core ICRF wave simulation to include realistic SOL plasmas", Nucl. Fusion in press], to larger and more complicated simulations by including a 3D realistic antenna and integrating RF rectified sheath potential model. Such an extension requires a scalable high fidelity 3D edge plasma wave simulation. We used the MFEM [http://mfem.org], open source scalable C++ finite element method library, and developed a Python wrapper for MFEM (PyMFEM), and then a radio frequency (RF) wave physics module in Python. This approach allows for building a physics layer rapidly, while separating the physics implementation being apart from the numerical FEM implementation. An interactive modeling interface was built on pScope [S Shiraiwa, et. al. Fusion Eng. Des. 112, 835] to work with an RF simulation model in a complicated geometry.

The graph neural network model.

PubMed

Scarselli, Franco; Gori, Marco; Tsoi, Ah Chung; Hagenbuchner, Markus; Monfardini, Gabriele

2009-01-01

Many underlying relationships among data in several areas of science and engineering, e.g., computer vision, molecular chemistry, molecular biology, pattern recognition, and data mining, can be represented in terms of graphs. In this paper, we propose a new neural network model, called graph neural network (GNN) model, that extends existing neural network methods for processing the data represented in graph domains. This GNN model, which can directly process most of the practically useful types of graphs, e.g., acyclic, cyclic, directed, and undirected, implements a function tau(G,n) is an element of IR(m) that maps a graph G and one of its nodes n into an m-dimensional Euclidean space. A supervised learning algorithm is derived to estimate the parameters of the proposed GNN model. The computational cost of the proposed algorithm is also considered. Some experimental results are shown to validate the proposed learning algorithm, and to demonstrate its generalization capabilities.

Communications network design and costing model technical manual

NASA Technical Reports Server (NTRS)

Logan, K. P.; Somes, S. S.; Clark, C. A.

1983-01-01

This computer model provides the capability for analyzing long-haul trunking networks comprising a set of user-defined cities, traffic conditions, and tariff rates. Networks may consist of all terrestrial connectivity, all satellite connectivity, or a combination of terrestrial and satellite connectivity. Network solutions provide the least-cost routes between all cities, the least-cost network routing configuration, and terrestrial and satellite service cost totals. The CNDC model allows analyses involving three specific FCC-approved tariffs, which are uniquely structured and representative of most existing service connectivity and pricing philosophies. User-defined tariffs that can be variations of these three tariffs are accepted as input to the model and allow considerable flexibility in network problem specification. The resulting model extends the domain of network analysis from traditional fixed link cost (distance-sensitive) problems to more complex problems involving combinations of distance and traffic-sensitive tariffs.

Two-phase vesicles: a study on evolutionary and stationary models.

PubMed

Sahebifard, MohammadMahdi; Shahidi, Alireza; Ziaei-Rad, Saeed

2017-05-01

In the current article, the dynamic evolution of two-phase vesicles is presented as an extension to a previous stationary model and based on an equilibrium of local forces. In the simplified model, ignoring the effects of membrane inertia, a dynamic equilibrium between the membrane bending potential and local fluid friction is considered in each phase. The equilibrium equations at the domain borders are completed by extended introduction of membrane section reactions. We show that in some cases, the results of stationary and evolutionary models are in agreement with each other and also with experimental observations, while in others the two models differ markedly. The value of our approach is that we can account for unresponsive points of uncertainty using our equations with the local velocity of the lipid membranes and calculating the intermediate states (shapes) in the consequent evolutionary, or response, path.

Implementing Accountable Care Organizations: Lessons From a Qualitative Analysis of Four Private Sector Organizations.

PubMed

Walker, Daniel M; Hefner, Jennifer L; Sova, Lindsey N; Hilligoss, Brian; Song, Paula H; McAlearney, Ann Scheck

Accountable care organizations (ACOs) are emerging across the healthcare marketplace and now include Medicare, Medicaid, and private sector payers covering more than 24 million lives. However, little is known about the process of organizational change required to achieve cost savings and quality improvements from the ACO model. This study applies the complex innovation implementation framework to understand the challenges and facilitators associated with the ACO implementation process. We conducted four case studies of private sector ACOs, selected to achieve variation in terms of geography and organizational maturity. Across sites, we used semistructured interviews with 68 key informants to elicit information regarding ACO implementation. Our analysis found challenges and facilitators across all domains in the conceptual framework. Notably, our findings deviated from the framework in two ways. First, findings from the financial resource availability domain revealed both financial and nonfinancial (i.e., labor) resources that contributed to implementation effectiveness. Second, a new domain, patient engagement, emerged as an important factor in implementation effectiveness. We present these deviations in an adapted framework. As the ACO model proliferates, these findings can support implementation efforts, and they highlight the importance of focusing on patients throughout the process. Importantly, this study extends the complex innovation implementation framework to incorporate consumers into the implementation framework, making it more patient centered and aiding future efforts.

Use of the Fracture Continuum Model for Numerical Modeling of Flow and Transport of Deep Geologic Disposal of Nuclear Waste in Crystalline Rock

NASA Astrophysics Data System (ADS)

Hadgu, T.; Kalinina, E.; Klise, K. A.; Wang, Y.

2015-12-01

Numerical modeling of disposal of nuclear waste in a deep geologic repository in fractured crystalline rock requires robust characterization of fractures. Various methods for fracture representation in granitic rocks exist. In this study we used the fracture continuum model (FCM) to characterize fractured rock for use in the simulation of flow and transport in the far field of a generic nuclear waste repository located at 500 m depth. The FCM approach is a stochastic method that maps the permeability of discrete fractures onto a regular grid. The method generates permeability fields using field observations of fracture sets. The original method described in McKenna and Reeves (2005) was designed for vertical fractures. The method has since then been extended to incorporate fully three-dimensional representations of anisotropic permeability, multiple independent fracture sets, and arbitrary fracture dips and orientations, and spatial correlation (Kalinina et al. 20012, 2014). For this study the numerical code PFLOTRAN (Lichtner et al., 2015) has been used to model flow and transport. PFLOTRAN solves a system of generally nonlinear partial differential equations describing multiphase, multicomponent and multiscale reactive flow and transport in porous materials. The code is designed to run on massively parallel computing architectures as well as workstations and laptops (e.g. Hammond et al., 2011). Benchmark tests were conducted to simulate flow and transport in a specified model domain. Distributions of fracture parameters were used to generate a selected number of realizations. For each realization, the FCM method was used to generate a permeability field of the fractured rock. The PFLOTRAN code was then used to simulate flow and transport in the domain. Simulation results and analysis are presented. The results indicate that the FCM approach is a viable method to model fractured crystalline rocks. The FCM is a computationally efficient way to generate realistic representation of complex fracture systems. This approach is of interest for nuclear waste disposal models applied over large domains.

The Spatial Scale of Convective Aggregation in Cloud Resolving Simulations of Radiative Convective Equilibrium

NASA Astrophysics Data System (ADS)

Patrizio, Casey

A three-dimensional cloud-resolving model (CRM) was used to investigate the preferred separation distance between humid, rainy regions formed by convective aggregation in radiative-convective equilibrium without rotation. We performed the simulations with doubly-periodic square domains of widths 768 km, 1536 km and 3072 km over a time period of about 200 days. The simulations in the larger domains were initialized using multiple copies of the results in the small domain at day 90, plus a small perturbation. With all three domain sizes, the simulations evolved to a single statistically steady convective cluster surrounded by a broader region of dry, subsiding air by about day 150. In the largest domain case, however, we found that an additional convective cluster formed when we the simulation was run for an extended period of time. Specifically, a smaller convective cluster formed at around day 185 at a maximum radial distance from the larger cluster and then re-merged with the larger cluster after about 10 days. We explored how the aggregated state was different in each domain case, before the smaller cluster formed in the large domain. In particular, we investigated changes in the radial structure of the aggregated state by calculating profiles for the water, dynamics and radiation as a function of distance from the center of the convective region. Changes in the vertical structure were also investigated by compositing on the convective region and dry, subsiding region at each height. We found that, with increasing domain size, the convective region boundary layer became more buoyant, the convective cores reached deeper into the troposphere, the mesoscale convective updraft became weaker, and the mesoscale convective region spread out. Additionally, as the domain size was increased, conditions in the remote environment became favorable for convection. We describe a physical mechanism for the weakening of the mesoscale convective updraft and associated broadening of the convective region with increasing domain size, which involves mid-level stable layer enhancement as a result of the deeper convection. Finally, a simple analytical model of the aggregated state was used to explore the dependency of the convective fractional area on the domain size. The simple model solutions that had net radiative cooling and surface evaporation in the convective region were consistent with the simulation results. In particular, the solutions captured the broadening of the convective region, the weakening of the convective region updraft, as well as the positive and declining gross moist stability (GMS) that occurred with increasing domain size in the simulations. Furthermore, the simple model transitioned from positive to negative GMS at a domain length of about 7000 km because the convective region boundary layer became progressively more humid with increasing domain size. This suggests that the spatial scale of the aggregated RCE state in the simulations would be limited to a length scale of about 7000 km, as convectively-active areas are commonly observed to have positive GMS. This work additionally suggests that the processes that influence the water vapor content in the convective region boundary layer, such as convectively-driven turbulent water vapor fluxes, are important for determining the spatial scale of the aggregated RCE state.

Probing the electrostatics and pharmacologic modulation of sequence-specific binding by the DNA-binding domain of the ETS-family transcription factor PU.1: a binding affinity and kinetics investigation

PubMed Central

Munde, Manoj; Poon, Gregory M. K.; Wilson, W. David

2013-01-01

Members of the ETS family of transcription factors regulate a functionally diverse array of genes. All ETS proteins share a structurally-conserved but sequence-divergent DNA-binding domain, known as the ETS domain. Although the structure and thermodynamics of the ETS-DNA complexes are well known, little is known about the kinetics of sequence recognition, a facet that offers potential insight into its molecular mechanism. We have characterized DNA binding by the ETS domain of PU.1 by biosensor-surface plasmon resonance (SPR). SPR analysis revealed a striking kinetic profile for DNA binding by the PU.1 ETS domain. At low salt concentrations, it binds high-affinity cognate DNA with a very slow association rate constant (≤105 M−1 s−1), compensated by a correspondingly small dissociation rate constant. The kinetics are strongly salt-dependent but mutually balance to produce a relatively weak dependence in the equilibrium constant. This profile contrasts sharply with reported data for other ETS domains (e.g., Ets-1, TEL) for which high-affinity binding is driven by rapid association (>107 M−1 s−1). We interpret this difference in terms of the hydration properties of ETS-DNA binding and propose that at least two mechanisms of sequence recognition are employed by this family of DNA-binding domain. Additionally, we use SPR to demonstrate the potential for pharmacological inhibition of sequence-specific ETS-DNA binding, using the minor groove-binding distamycin as a model compound. Our work establishes SPR as a valuable technique for extending our understanding of the molecular mechanisms of ETS-DNA interactions as well as developing potential small-molecule agents for biotechnological and therapeutic purposes. PMID:23416556

The structural basis for the functional comparability of factor VIII and the long-acting variant recombinant factor VIII Fc fusion protein

DOE PAGES

Leksa, N. C.; Chiu, P. -L.; Bou-Assaf, G. M.; ...

2017-05-03

Fusion of the human IgG 1 Fc domain to the C-terminal C2 domain of B-domain-deleted (BDD) factor VIII (FVIII) results in the recombinant FVIII Fc (rFVIIIFc) fusion protein, which has a 1.5-fold longer half-life in humans. To assess the structural properties of rFVIIIFc by comparing its constituent FVIII and Fc elements with their respective isolated components, and evaluating their structural independence within rFVIIIFc. rFVIIIFc and its isolated FVIII and Fc components were compared by the use of hydrogen–deuterium exchange mass spectrometry (HDX-MS). The structure of rFVIIIFc was also evaluated by the use of X-ray crystallography, small-angle X-ray scattering (SAXS), andmore » electron microscopy (EM). The degree of steric interference by the appended Fc domain was assessed by EM and surface plasmon resonance (SPR). HDX-MS analysis of rFVIIIFc revealed that fusion caused no structural perturbations in FVIII or Fc. The rFVIIIFc crystal structure showed that the FVIII component is indistinguishable from published BDD FVIII structures. The Fc domain was not observed, indicating high mobility. SAXS analysis was consistent with an ensemble of rigid-body models in which the Fc domain exists in a largely extended orientation relative to FVIII. Binding of Fab fragments of anti-C2 domain antibodies to BDD FVIII was visualized by EM, and the affinities of the corresponding intact antibodies for BDD FVIII and rFVIIIFc were comparable by SPR analysis. Thus, the FVIII and Fc components of rFVIIIFc are structurally indistinguishable from their isolated constituents, and show a high degree of structural independence, consistent with the functional comparability of rFVIIIFc and unmodified FVIII.« less

The structural basis for the functional comparability of Factor VIII and the long-acting variant recombinant Factor VIII Fc fusion protein

PubMed Central

Leksa, N.C.; Chiu, P.-L.; Bou-Assaf, G.M.; Quan, C.; Liu, Z.; Goodman, A.B.; Chambers, M.G.; Tsutakawa, S.E.; Hammel, M.; Peters, R.T.; Walz, T.; Kulman, J.D.

2017-01-01

SUMMARY Background Fusion of the human IgG1 Fc domain to the C-terminal C2 domain of B domain-deleted (BDD) factor VIII (FVIII) results in the rFVIIIFc fusion protein that has a 1.5-fold longer half-life in humans. Objective To assess the structural properties of rFVIIIFc by comparing its constituent FVIII and Fc elements with their respective isolated components and evaluating their structural independence within rFVIIIFc. Methods rFVIIIFc and its isolated FVIII and Fc components were compared by hydrogen-deuterium exchange mass spectrometry (HDX-MS). The structure of rFVIIIFc was also evaluated by X-ray crystallography, small-angle X-ray scattering (SAXS), and electron microscopy (EM). The degree of steric interference by the appended Fc domain was assessed by EM and surface plasmon resonance (SPR). Results HDX-MS analysis of rFVIIIFc revealed that fusion caused no structural perturbations in FVIII or Fc. The rFVIIIFc crystal structure showed that the FVIII component is indistinguishable from published BDD FVIII structures. The Fc domain was not observed, indicating high mobility. SAXS analysis was consistent with an ensemble of rigid-body models in which the Fc domain exists in a largely extended orientation relative to FVIII. Binding of Fab fragments of anti-C2 domain antibodies to BDD FVIII was visualized by EM, and the affinities of the corresponding intact antibodies for BDD FVIII and rFVIIIFc were comparable by SPR analysis. Conclusions The FVIII and Fc components of rFVIIIFc are structurally indistinguishable from their isolated constituents and exhibit a high degree of structural independence, consistent with the functional comparability of rFVIIIFc and unmodified FVIII. PMID:28397397

Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways

PubMed Central

Willett, Julia L. E.; Gucinski, Grant C.; Fatherree, Jackson P.; Low, David A.; Hayes, Christopher S.

2015-01-01

Contact-dependent growth inhibition (CDI) systems function to deliver toxins into neighboring bacterial cells. CDI+ bacteria export filamentous CdiA effector proteins, which extend from the inhibitor-cell surface to interact with receptors on neighboring target bacteria. Upon binding its receptor, CdiA delivers a toxin derived from its C-terminal region. CdiA C-terminal (CdiA-CT) sequences are highly variable between bacteria, reflecting the multitude of CDI toxin activities. Here, we show that several CdiA-CT regions are composed of two domains, each with a distinct function during CDI. The C-terminal domain typically possesses toxic nuclease activity, whereas the N-terminal domain appears to control toxin transport into target bacteria. Using genetic approaches, we identified ptsG, metI, rbsC, gltK/gltJ, yciB, and ftsH mutations that confer resistance to specific CdiA-CTs. The resistance mutations all disrupt expression of inner-membrane proteins, suggesting that these proteins are exploited for toxin entry into target cells. Moreover, each mutation only protects against inhibition by a subset of CdiA-CTs that share similar N-terminal domains. We propose that, following delivery of CdiA-CTs into the periplasm, the N-terminal domains bind specific inner-membrane receptors for subsequent translocation into the cytoplasm. In accord with this model, we find that CDI nuclease domains are modular payloads that can be redirected through different import pathways when fused to heterologous N-terminal “translocation domains.” These results highlight the plasticity of CDI toxin delivery and suggest that the underlying translocation mechanisms could be harnessed to deliver other antimicrobial agents into Gram-negative bacteria. PMID:26305955

The structural basis for the functional comparability of factor VIII and the long-acting variant recombinant factor VIII Fc fusion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leksa, N. C.; Chiu, P. -L.; Bou-Assaf, G. M.

Fusion of the human IgG 1 Fc domain to the C-terminal C2 domain of B-domain-deleted (BDD) factor VIII (FVIII) results in the recombinant FVIII Fc (rFVIIIFc) fusion protein, which has a 1.5-fold longer half-life in humans. To assess the structural properties of rFVIIIFc by comparing its constituent FVIII and Fc elements with their respective isolated components, and evaluating their structural independence within rFVIIIFc. rFVIIIFc and its isolated FVIII and Fc components were compared by the use of hydrogen–deuterium exchange mass spectrometry (HDX-MS). The structure of rFVIIIFc was also evaluated by the use of X-ray crystallography, small-angle X-ray scattering (SAXS), andmore » electron microscopy (EM). The degree of steric interference by the appended Fc domain was assessed by EM and surface plasmon resonance (SPR). HDX-MS analysis of rFVIIIFc revealed that fusion caused no structural perturbations in FVIII or Fc. The rFVIIIFc crystal structure showed that the FVIII component is indistinguishable from published BDD FVIII structures. The Fc domain was not observed, indicating high mobility. SAXS analysis was consistent with an ensemble of rigid-body models in which the Fc domain exists in a largely extended orientation relative to FVIII. Binding of Fab fragments of anti-C2 domain antibodies to BDD FVIII was visualized by EM, and the affinities of the corresponding intact antibodies for BDD FVIII and rFVIIIFc were comparable by SPR analysis. Thus, the FVIII and Fc components of rFVIIIFc are structurally indistinguishable from their isolated constituents, and show a high degree of structural independence, consistent with the functional comparability of rFVIIIFc and unmodified FVIII.« less

The Heliophysics Integrated Observatory

NASA Astrophysics Data System (ADS)

Csillaghy, A.; Bentley, R. D.

2009-12-01

HELIO is a new Europe-wide, FP7-funded distributed network of services that will address the needs of a broad community of researchers in heliophysics. This new research field explores the “Sun-Solar System Connection” and requires the joint exploitation of solar, heliospheric, magnetospheric and ionospheric observations. HELIO will provide the most comprehensive integrated information system in this domain; it will coordinate access to the distributed resources needed by the community, and will provide access to services to mine and analyse the data. HELIO will be designed as a Service-oriented Architecture. The initial infrastructure will include services based on metadata and data servers deployed by the European Grid of Solar Observations (EGSO). We will extend these to address observations from all the disciplines of heliophysics; differences in the way the domains describe and handle the data will be resolved using semantic mapping techniques. Processing and storage services will allow the user to explore the data and create the products that meet stringent standards of interoperability. These capabilities will be orchestrated with the data and metadata services using the Taverna workflow tool. HELIO will address the challenges along the FP7 I3 activities model: (1) Networking: we will cooperate closely with the community to define new standards for heliophysics and the required capabilities of the HELIO system. (2) Services: we will integrate the services developed by the project and other groups to produce an infrastructure that can easily be extended to satisfy the growing and changing needs of the community. (3) Joint Research: we will develop search tools that span disciplinary boundaries and explore new types of user-friendly interfaces HELIO will be a key component of a worldwide effort to integrate heliophysics data and will coordinate closely with international organizations to exploit synergies with complementary domains.

A tensegrity model for hydrogen bond networks in proteins.

PubMed

Bywater, Robert P

2017-05-01

Hydrogen-bonding networks in proteins considered as structural tensile elements are in balance separately from any other stabilising interactions that may be in operation. The hydrogen bond arrangement in the network is reminiscent of tensegrity structures in architecture and sculpture. Tensegrity has been discussed before in cells and tissues and in proteins. In contrast to previous work only hydrogen bonds are studied here. The other interactions within proteins are either much stronger - covalent bonds connecting the atoms in the molecular skeleton or weaker forces like the so-called hydrophobic interactions. It has been demonstrated that the latter operate independently from hydrogen bonds. Each category of interaction must, if the protein is to have a stable structure, balance out. The hypothesis here is that the entire hydrogen bond network is in balance without any compensating contributions from other types of interaction. For sidechain-sidechain, sidechain-backbone and backbone-backbone hydrogen bonds in proteins, tensegrity balance ("closure") is required over the entire length of the polypeptide chain that defines individually folding units in globular proteins ("domains") as well as within the repeating elements in fibrous proteins that consist of extended chain structures. There is no closure to be found in extended structures that do not have repeating elements. This suggests an explanation as to why globular domains, as well as the repeat units in fibrous proteins, have to have a defined number of residues. Apart from networks of sidechain-sidechain hydrogen bonds there are certain key points at which this closure is achieved in the sidechain-backbone hydrogen bonds and these are associated with demarcation points at the start or end of stretches of secondary structure. Together, these three categories of hydrogen bond achieve the closure that is necessary for the stability of globular protein domains as well as repeating elements in fibrous proteins.

The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

PubMed Central

Galloway-Peña, Jessica R.; Liang, Xiaowen; Singh, Kavindra V.; Yadav, Puja; Chang, Chungyu; La Rosa, Sabina Leanti; Shelburne, Samuel; Ton-That, Hung; Höök, Magnus

2014-01-01

The WxL domain recently has been identified as a novel cell wall binding domain found in numerous predicted proteins within multiple Gram-positive bacterial species. However, little is known about the function of proteins containing this novel domain. Here, we identify and characterize 6 Enterococcus faecium proteins containing the WxL domain which, by reverse transcription-PCR (RT-PCR) and genomic analyses, are located in three similarly organized operons, deemed WxL loci A, B, and C. Western blotting, electron microscopy, and enzyme-linked immunosorbent assays (ELISAs) determined that genes of WxL loci A and C encode antigenic, cell surface proteins exposed at higher levels in clinical isolates than in commensal isolates. Secondary structural analyses of locus A recombinant WxL domain-containing proteins found they are rich in β-sheet structure and disordered segments. Using Biacore analyses, we discovered that recombinant WxL proteins from locus A bind human extracellular matrix proteins, specifically type I collagen and fibronectin. Proteins encoded by locus A also were found to bind to each other, suggesting a novel cell surface complex. Furthermore, bile salt survival assays and animal models using a mutant from which all three WxL loci were deleted revealed the involvement of WxL operons in bile salt stress and endocarditis pathogenesis. In summary, these studies extend our understanding of proteins containing the WxL domain and their potential impact on colonization and virulence in E. faecium and possibly other Gram-positive bacterial species. PMID:25512313

Multi-disciplinary optimization of aeroservoelastic systems

NASA Technical Reports Server (NTRS)

Karpel, Mardechay

1992-01-01

The purpose of the research project was to continue the development of new methods for efficient aeroservoelastic analysis and optimization. The main targets were as follows: to complete the development of analytical tools for the investigation of flutter with large stiffness changes; to continue the work on efficient continuous gust response and sensitivity derivatives; and to advance the techniques of calculating dynamic loads with control and unsteady aerodynamic effects. An efficient and highly accurate mathematical model for time-domain analysis of flutter during which large structural changes occur was developed in cooperation with Carol D. Wieseman of NASA LaRC. The model was based on the second-year work 'Modal Coordinates for Aeroelastic Analysis with Large Local Structural Variations'. The work on continuous gust response was completed. An abstract of the paper 'Continuous Gust Response and Sensitivity Derivatives Using State-Space Models' was submitted for presentation in the 33rd Israel Annual Conference on Aviation and Astronautics, Feb. 1993. The abstract is given in Appendix A. The work extends the optimization model to deal with continuous gust objectives in a way that facilitates their inclusion in the efficient multi-disciplinary optimization scheme. Currently under development is a work designed to extend the analysis and optimization capabilities to loads and stress considerations. The work is on aircraft dynamic loads in response to impulsive and non-impulsive excitation. The work extends the formulations of the mode-displacement and summation-of-forces methods to include modes with significant local distortions, and load modes. An abstract of the paper,'Structural Dynamic Loads in Response to Impulsive Excitation' is given in appendix B. Another work performed this year under the Grant was 'Size-Reduction Techniques for the Determination of Efficient Aeroservoelastic Models' given in Appendix C.

Using neighborhood cohesiveness to infer interactions between protein domains.

PubMed

Segura, Joan; Sorzano, C O S; Cuenca-Alba, Jesus; Aloy, Patrick; Carazo, J M

2015-08-01

In recent years, large-scale studies have been undertaken to describe, at least partially, protein-protein interaction maps, or interactomes, for a number of relevant organisms, including human. However, current interactomes provide a somehow limited picture of the molecular details involving protein interactions, mostly because essential experimental information, especially structural data, is lacking. Indeed, the gap between structural and interactomics information is enlarging and thus, for most interactions, key experimental information is missing. We elaborate on the observation that many interactions between proteins involve a pair of their constituent domains and, thus, the knowledge of how protein domains interact adds very significant information to any interactomic analysis. In this work, we describe a novel use of the neighborhood cohesiveness property to infer interactions between protein domains given a protein interaction network. We have shown that some clustering coefficients can be extended to measure a degree of cohesiveness between two sets of nodes within a network. Specifically, we used the meet/min coefficient to measure the proportion of interacting nodes between two sets of nodes and the fraction of common neighbors. This approach extends previous works where homolog coefficients were first defined around network nodes and later around edges. The proposed approach substantially increases both the number of predicted domain-domain interactions as well as its accuracy as compared with current methods. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Magnetospheric Constellation Mission. Dynamic Response and Coupling Observatory (DRACO): Understanding the Global Dynamics of the Structured Magnetotail

NASA Technical Reports Server (NTRS)

2001-01-01

Magnetospheric Constellation Dynamic Response and Coupling Observatory (DRACO) is the Solar Terrestrial Probe (STP) designed to understand the nonlinear dynamics, responses, and connections within the Earth's structured magnetotail, using a constellation of approximately 50 to 100 distributed vector measurement spacecraft. DRACO will reveal magnetotail processes operating within a domain extending 20 Earth radii (R(sub E)) across the tail and 40 R(sub E)down the tail, on spatial and time scales accessible to global circulation models, i.e., approximately 2 R(sub E) and 10 seconds.

Gendered production and consumption in rural Africa

PubMed Central

Kevane, Michael

2012-01-01

Recent research underscores the continued importance of gender in rural Africa. Analysis of interactions within households is becoming more sophisticated and continues to reject the unitary model. There is some evidence of discriminatory treatment of girls relative to boys, although the magnitudes of differential investments in health and schooling are not large and choices seem quite responsive to changes in opportunity costs. Social norms proscribing and prescribing male and female economic behavior remain substantial, extending into many domains, especially land tenure. Gender constructions are constantly evolving, although there is little evidence of rapid, transformative change in rural areas.

Analytic gravitational waveforms for generic precessing compact binaries

NASA Astrophysics Data System (ADS)

Chatziioannou, Katerina; Klein, Antoine; Cornish, Neil; Yunes, Nicolas

2017-01-01

Gravitational waves from compact binaries are subject to amplitude and phase modulations arising from interactions between the angular momenta of the system. Failure to account for such spin-precession effects in gravitational wave data analysis could hinder detection and completely ruin parameter estimation. In this talk I will describe the construction of closed-form, frequency-domain waveforms for fully-precessing, quasi-circular binary inspirals. The resulting waveforms can model spinning binaries of arbitrary spin magnitudes, spin orientations, and masses during the inspiral phase. I will also describe ongoing efforts to extend these inspiral waveforms to the merger and ringdown phases.

Data-driven parameterization of the generalized Langevin equation

DOE PAGES

Lei, Huan; Baker, Nathan A.; Li, Xiantao

2016-11-29

We present a data-driven approach to determine the memory kernel and random noise of the generalized Langevin equation. To facilitate practical implementations, we parameterize the kernel function in the Laplace domain by a rational function, with coefficients directly linked to the equilibrium statistics of the coarse-grain variables. Further, we show that such an approximation can be constructed to arbitrarily high order. Within these approximations, the generalized Langevin dynamics can be embedded in an extended stochastic model without memory. We demonstrate how to introduce the stochastic noise so that the fluctuation-dissipation theorem is exactly satisfied.

Steepest entropy ascent model for far-nonequilibrium thermodynamics: Unified implementation of the maximum entropy production principle

NASA Astrophysics Data System (ADS)

Beretta, Gian Paolo

2014-10-01

By suitable reformulations, we cast the mathematical frameworks of several well-known different approaches to the description of nonequilibrium dynamics into a unified formulation valid in all these contexts, which extends to such frameworks the concept of steepest entropy ascent (SEA) dynamics introduced by the present author in previous works on quantum thermodynamics. Actually, the present formulation constitutes a generalization also for the quantum thermodynamics framework. The analysis emphasizes that in the SEA modeling principle a key role is played by the geometrical metric with respect to which to measure the length of a trajectory in state space. In the near-thermodynamic-equilibrium limit, the metric tensor is directly related to the Onsager's generalized resistivity tensor. Therefore, through the identification of a suitable metric field which generalizes the Onsager generalized resistance to the arbitrarily far-nonequilibrium domain, most of the existing theories of nonequilibrium thermodynamics can be cast in such a way that the state exhibits the spontaneous tendency to evolve in state space along the path of SEA compatible with the conservation constraints and the boundary conditions. The resulting unified family of SEA dynamical models is intrinsically and strongly consistent with the second law of thermodynamics. The non-negativity of the entropy production is a general and readily proved feature of SEA dynamics. In several of the different approaches to nonequilibrium description we consider here, the SEA concept has not been investigated before. We believe it defines the precise meaning and the domain of general validity of the so-called maximum entropy production principle. Therefore, it is hoped that the present unifying approach may prove useful in providing a fresh basis for effective, thermodynamically consistent, numerical models and theoretical treatments of irreversible conservative relaxation towards equilibrium from far nonequilibrium states. The mathematical frameworks we consider are the following: (A) statistical or information-theoretic models of relaxation; (B) small-scale and rarefied gas dynamics (i.e., kinetic models for the Boltzmann equation); (C) rational extended thermodynamics, macroscopic nonequilibrium thermodynamics, and chemical kinetics; (D) mesoscopic nonequilibrium thermodynamics, continuum mechanics with fluctuations; and (E) quantum statistical mechanics, quantum thermodynamics, mesoscopic nonequilibrium quantum thermodynamics, and intrinsic quantum thermodynamics.

Finite difference time domain calculation of transients in antennas with nonlinear loads

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.; Kunz, Karl S.; Chamberlin, Kent

1991-01-01

Determining transient electromagnetic fields in antennas with nonlinear loads is a challenging problem. Typical methods used involve calculating frequency domain parameters at a large number of different frequencies, then applying Fourier transform methods plus nonlinear equation solution techniques. If the antenna is simple enough so that the open circuit time domain voltage can be determined independently of the effects of the nonlinear load on the antennas current, time stepping methods can be applied in a straightforward way. Here, transient fields for antennas with more general geometries are calculated directly using Finite Difference Time Domain (FDTD) methods. In each FDTD cell which contains a nonlinear load, a nonlinear equation is solved at each time step. As a test case, the transient current in a long dipole antenna with a nonlinear load excited by a pulsed plane wave is computed using this approach. The results agree well with both calculated and measured results previously published. The approach given here extends the applicability of the FDTD method to problems involving scattering from targets, including nonlinear loads and materials, and to coupling between antennas containing nonlinear loads. It may also be extended to propagation through nonlinear materials.

A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated

PubMed Central

Fischer, Kathleen E.; Hoffman, Jessica M.; Sloane, Lauren B.; Gelfond, Jonathan A.L.; Soto, Vanessa Y.; Richardson, Arlan G.; Austad, Steven N.

2016-01-01

Lifespan provides a discrete metric that is intuitively appealing and the assumption has been that healthspan is extended concomitant with lifespan. Medicine has been more successful at extending life than preserving health during aging. Interventions that extend lifespan in model organisms do not always result in a corresponding increase in healthspan, suggesting that lifespan and healthspan may be uncoupled. To understand how interventions that extend life affect healthspan, we need measures that distinguish between young and old animals. Here we measured age-related changes in healthspan in male and female C57BL/6JNia mice assessed at 4 distinct ages (4 months, 20 months, 28 months and 32 months). Correlations between health parameters and age varied. Some parameters show consistent patterns with age across studies and in both sexes, others changed in one sex only and others showed no significant differences in mice of different ages. Few correlations existed among health assays, suggesting that physiological function in domains we assessed change independently in aging mice. With one exception, health parameters were not significantly associated with an increased probability of premature death. Our results show the need for more robust measures of murine health and suggest a potential disconnect between health and lifespan in mice. PMID:27705904

Modeling extracellular fields for a three-dimensional network of cells using NEURON.

PubMed

Appukuttan, Shailesh; Brain, Keith L; Manchanda, Rohit

2017-10-01

Computational modeling of biological cells usually ignores their extracellular fields, assuming them to be inconsequential. Though such an assumption might be justified in certain cases, it is debatable for networks of tightly packed cells, such as in the central nervous system and the syncytial tissues of cardiac and smooth muscle. In the present work, we demonstrate a technique to couple the extracellular fields of individual cells within the NEURON simulation environment. The existing features of the simulator are extended by explicitly defining current balance equations, resulting in the coupling of the extracellular fields of adjacent cells. With this technique, we achieved continuity of extracellular space for a network model, thereby allowing the exploration of extracellular interactions computationally. Using a three-dimensional network model, passive and active electrical properties were evaluated under varying levels of extracellular volumes. Simultaneous intracellular and extracellular recordings for synaptic and action potentials were analyzed, and the potential of ephaptic transmission towards functional coupling of cells was explored. We have implemented a true bi-domain representation of a network of cells, with the extracellular domain being continuous throughout the entire model. This has hitherto not been achieved using NEURON, or other compartmental modeling platforms. We have demonstrated the coupling of the extracellular field of every cell in a three-dimensional model to obtain a continuous uniform extracellular space. This technique provides a framework for the investigation of interactions in tightly packed networks of cells via their extracellular fields. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved hydrophilic interaction chromatography LC/MS of heparinoids using a chip with postcolumn makeup flow.

PubMed

Staples, Gregory O; Naimy, Hicham; Yin, Hongfeng; Kileen, Kevin; Kraiczek, Karsten; Costello, Catherine E; Zaia, Joseph

2010-01-15

Heparan sulfate (HS) and heparin are linear, heterogeneous carbohydrates of the glycosaminoglycan (GAG) family that are modified by N-acetylation, N-sulfation, O-sulfation, and uronic acid epimerization. HS interacts with growth factors in the extracellular matrix, thereby modulating signaling pathways that govern cell growth, development, differentiation, proliferation, and adhesion. High-performance liquid chromatography (HPLC)-chip-based hydrophilic interaction liquid chromatography/mass spectrometry has emerged as a method for analyzing the domain structure of GAGs. However, analysis of highly sulfated GAG structures decasaccharide or larger in size has been limited by spray instability in the negative-ion mode. This report demonstrates that addition of postcolumn makeup flow to the amide-HPLC-chip configuration permits robust and reproducible analysis of extended GAG domains (up to degree of polymerization 18) from HS and heparin. This platform provides quantitative information regarding the oligosaccharide profile, degree of sulfation, and nonreducing chain termini. It is expected that this technology will enable quantitative, comparative glycomics profiling of extended GAG oligosaccharide domains of functional interest.

Structural and Genetic Analyses of the Mycobacterium tuberculosis Protein Kinase B Sensor Domain Identify a Potential Ligand-binding Site.

PubMed

Prigozhin, Daniil M; Papavinasasundaram, Kadamba G; Baer, Christina E; Murphy, Kenan C; Moskaleva, Alisa; Chen, Tony Y; Alber, Tom; Sassetti, Christopher M

2016-10-28

Monitoring the environment with serine/threonine protein kinases is critical for growth and survival of Mycobacterium tuberculosis, a devastating human pathogen. Protein kinase B (PknB) is a transmembrane serine/threonine protein kinase that acts as an essential regulator of mycobacterial growth and division. The PknB extracellular domain (ECD) consists of four repeats homologous to penicillin-binding protein and serine/threonine kinase associated (PASTA) domains, and binds fragments of peptidoglycan. These properties suggest that PknB activity is modulated by ECD binding to peptidoglycan substructures, however, the molecular mechanisms underpinning PknB regulation remain unclear. In this study, we report structural and genetic characterization of the PknB ECD. We determined the crystal structures of overlapping ECD fragments at near atomic resolution, built a model of the full ECD, and discovered a region on the C-terminal PASTA domain that has the properties of a ligand-binding site. Hydrophobic interaction between this surface and a bound molecule of citrate was observed in a crystal structure. Our genetic analyses in M. tuberculosis showed that nonfunctional alleles were produced either by deletion of any of single PASTA domain or by mutation of individual conserved residues lining the putative ligand-binding surface of the C-terminal PASTA repeat. These results define two distinct structural features necessary for PknB signal transduction, a fully extended ECD and a conserved, membrane-distal putative ligand-binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.

PubMed

Zhang, Xu; Diekwisch, Thomas G H; Luan, Xianghong

2011-12-01

The functional significance of extracellular matrix proteins in the life of vertebrates is underscored by a high level of sequence variability in tandem with a substantial degree of conservation in terms of cell-cell and cell-matrix adhesion interactions. Many extracellular matrix proteins feature multiple adhesion domains for successful attachment to substrates, such as integrin, CD63, and heparin. Here we have used homology and ab initio modeling algorithms to compare mouse ameloblastin (mAMBN) and human ameloblastin (hABMN) isoforms and to analyze their potential for cell adhesion and interaction with other matrix molecules as well as calcium binding. Sequence comparison between mAMBN and hAMBN revealed a 26-amino-acid deletion in mAMBN, corresponding to a helix-loop-helix frameshift. The human AMBN domain (174Q-201G), homologous to the mAMBN 157E-178I helix-loop-helix region, formed a helix-loop motif with an extended loop, suggesting a higher degree of flexibility of hAMBN compared with mAMBN, as confirmed by molecular dynamics simulation. Heparin-binding domains, CD63-interaction domains, and calcium-binding sites in both hAMBN and mAMBN support the concept of AMBN as an extracellular matrix protein. The high level of conservation between AMBN functional domains related to adhesion and differentiation was remarkable when compared with only 61% amino acid sequence homology. © 2011 Eur J Oral Sci.

Predicting synchrony in heterogeneous pulse coupled oscillators

NASA Astrophysics Data System (ADS)

Talathi, Sachin S.; Hwang, Dong-Uk; Miliotis, Abraham; Carney, Paul R.; Ditto, William L.

2009-08-01

Pulse coupled oscillators (PCOs) represent an ubiquitous model for a number of physical and biological systems. Phase response curves (PRCs) provide a general mathematical framework to analyze patterns of synchrony generated within these models. A general theoretical approach to account for the nonlinear contributions from higher-order PRCs in the generation of synchronous patterns by the PCOs is still lacking. Here, by considering a prototypical example of a PCO network, i.e., two synaptically coupled neurons, we present a general theory that extends beyond the weak-coupling approximation, to account for higher-order PRC corrections in the derivation of an approximate discrete map, the stable fixed point of which can predict the domain of 1:1 phase locked synchronous states generated by the PCO network.

Enriching mission planning approach with state transition graph heuristics for deep space exploration

NASA Astrophysics Data System (ADS)

Jin, Hao; Xu, Rui; Xu, Wenming; Cui, Pingyuan; Zhu, Shengying

2017-10-01

As to support the mission of Mars exploration in China, automated mission planning is required to enhance security and robustness of deep space probe. Deep space mission planning requires modeling of complex operations constraints and focus on the temporal state transitions of involved subsystems. Also, state transitions are ubiquitous in physical systems, but have been elusive for knowledge description. We introduce a modeling approach to cope with these difficulties that takes state transitions into consideration. The key technique we build on is the notion of extended states and state transition graphs. Furthermore, a heuristics that based on state transition graphs is proposed to avoid redundant work. Finally, we run comprehensive experiments on selected domains and our techniques present an excellent performance.

The Cerebellum: Adaptive Prediction for Movement and Cognition

PubMed Central

Sokolov, Arseny A.; Miall, R. Chris; Ivry, Richard B.

2017-01-01

Over the past 30 years, cumulative evidence has indicated that cerebellar function extends beyond sensorimotor control. This view has emerged from studies of neuroanatomy, neuroimaging, neuropsychology and brain stimulation, with the results implicating the cerebellum in domains as diverse as attention, language, executive function and social cognition. Although the literature provides sophisticated models of how the cerebellum helps refine movements, it remains unclear how the core mechanisms of these models can be applied when considering a broader conceptualization of cerebellar function. In light of recent multidisciplinary findings, we consider two key concepts that have been suggested as general computational principles of cerebellar function, prediction and error-based learning, examining how these might be relevant in the operation of cognitive cerebro-cerebellar loops. PMID:28385461

An Extended Model of Knowledge Governance

NASA Astrophysics Data System (ADS)

Karvalics, Laszlo Z.; Dalal, Nikunj

In current times, we are seeing the emergence of a new paradigm to describe, understand, and analyze the expanding "knowledge domain". This overarching framework - called knowledge governance - draws from and builds upon knowledge management and may be seen as a kind of meta-layer of knowledge management. The emerging knowledge governance approach deals with issues that lie at the intersection of organization and knowledge processes. Knowledge governance has two main interpretation levels in the literature: the company- (micro-) and the national (macro-) level. We propose a three-layer model instead of the previous two-layer version, adding a layer of "global" knowledge governance. Analyzing and separating the main issues in this way, we can re-formulate the focus of knowledge governance research and practice in all layers.

A thermophilic mini-chaperonin contains a conserved polypeptide-binding surface: combined crystallographic and NMR studies of the GroEL Apical Domain with implications for substrate interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, Q. X. H.; Dementieva, I. S. D.; Walsh, M. A. W.

2001-02-23

A homologue of the Escherichia coli GroEL apical domain was obtained from thermophilic eubacterium Thermus thermophilus. The domains share 70 % sequence identity (101 out of 145 residues). The thermal stability of the T. thermophilus apical domain (T{sub m}>100{sup o}C as evaluated by circular dichroism) is at least 35{sup o}C greater than that of the E. coli apical domain (T{sub m}=65{sup o}C). The crystal structure of a selenomethione-substituted apical domain from T. thermophilus was determined to a resolution of 1.78 {angstrom} using multiwavelength-anomalous-diffraction phasing. The structure is similar to that of the E. coli apical domain (root-mean-square deviation 0.45 {angstrom}more » based on main-chain atoms). The thermophilic structure contains seven additional salt bridges of which four contain charge-stabilized hydrogen bonds. Only one of the additional salt bridges would face the 'Anfinsen cage' in GroEL. High temperatures were exploited to map sites of interactions between the apical domain and molten globules. NMR footprints of apical domain-protein complexes were obtained at elevated temperature using {sup 15}N-{sup 1}H correlation spectra of {sup 15}N-labeled apical domain. Footprints employing two polypeptides unrelated in sequence or structure (an insulin monomer and the SRY high-mobility-group box, each partially unfolded at 50{sup o}C) are essentially the same and consistent with the peptide-binding surface previously defined in E. coli GroEL and its apical domain-peptide complexes. An additional part of this surface comprising a short N-terminal {alpha}-helix is observed. The extended footprint rationalizes mutagenesis studies of intact GroEL in which point mutations affecting substrate binding were found outside the 'classical' peptide-binding site. Our results demonstrate structural conservation of the apical domain among GroEL homologues and conservation of an extended non-polar surface recognizing diverse polypeptides.« less

Prediction of heterotrimeric protein complexes by two-phase learning using neighboring kernels

PubMed Central

2014-01-01

Background Protein complexes play important roles in biological systems such as gene regulatory networks and metabolic pathways. Most methods for predicting protein complexes try to find protein complexes with size more than three. It, however, is known that protein complexes with smaller sizes occupy a large part of whole complexes for several species. In our previous work, we developed a method with several feature space mappings and the domain composition kernel for prediction of heterodimeric protein complexes, which outperforms existing methods. Results We propose methods for prediction of heterotrimeric protein complexes by extending techniques in the previous work on the basis of the idea that most heterotrimeric protein complexes are not likely to share the same protein with each other. We make use of the discriminant function in support vector machines (SVMs), and design novel feature space mappings for the second phase. As the second classifier, we examine SVMs and relevance vector machines (RVMs). We perform 10-fold cross-validation computational experiments. The results suggest that our proposed two-phase methods and SVM with the extended features outperform the existing method NWE, which was reported to outperform other existing methods such as MCL, MCODE, DPClus, CMC, COACH, RRW, and PPSampler for prediction of heterotrimeric protein complexes. Conclusions We propose two-phase prediction methods with the extended features, the domain composition kernel, SVMs and RVMs. The two-phase method with the extended features and the domain composition kernel using SVM as the second classifier is particularly useful for prediction of heterotrimeric protein complexes. PMID:24564744

Wide-band profile domain pulsar timing analysis

NASA Astrophysics Data System (ADS)

Lentati, L.; Kerr, M.; Dai, S.; Hobson, M. P.; Shannon, R. M.; Hobbs, G.; Bailes, M.; Bhat, N. D. Ramesh; Burke-Spolaor, S.; Coles, W.; Dempsey, J.; Lasky, P. D.; Levin, Y.; Manchester, R. N.; Osłowski, S.; Ravi, V.; Reardon, D. J.; Rosado, P. A.; Spiewak, R.; van Straten, W.; Toomey, L.; Wang, J.; Wen, L.; You, X.; Zhu, X.

2017-04-01

We extend profile domain pulsar timing to incorporate wide-band effects such as frequency-dependent profile evolution and broad-band shape variation in the pulse profile. We also incorporate models for temporal variations in both pulse width and in the separation in phase of the main pulse and interpulse. We perform the analysis with both nested sampling and Hamiltonian Monte Carlo methods. In the latter case, we introduce a new parametrization of the posterior that is extremely efficient in the low signal-to-noise regime and can be readily applied to a wide range of scientific problems. We apply this methodology to a series of simulations, and to between seven and nine years of observations for PSRs J1713+0747, J1744-1134 and J1909-3744 with frequency coverage that spans 700-3600 Mhz. We use a smooth model for profile evolution across the full frequency range, and compare smooth and piecewise models for the temporal variations in dispersion measure (DM). We find that the profile domain framework consistently results in improved timing precision compared to the standard analysis paradigm by as much as 40 per cent for timing parameters. Incorporating smoothness in the DM variations into the model further improves timing precision by as much as 30 per cent. For PSR J1713+0747, we also detect pulse shape variation uncorrelated between epochs, which we attribute to variation intrinsic to the pulsar at a level consistent with previously published analyses. Not accounting for this shape variation biases the measured arrival times at the level of ˜30 ns, the same order of magnitude as the expected shift due to gravitational waves in the pulsar timing band.

Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels*

PubMed Central

Du, Yuzhe; Nomura, Yoshiko; Zhorov, Boris S.; Dong, Ke

2016-01-01

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoor residual spraying of DDT is still recommended for malaria control in Africa. Development of resistance to DDT and pyrethroids is a serious global obstacle for managing disease vectors. Mapping DDT binding sites is necessary for understanding mechanisms of resistance and modulation of sodium channels by structurally different ligands. The pioneering model of the housefly sodium channel visualized the first receptor for pyrethroids, PyR1, in the II/III domain interface and suggested that DDT binds within PyR1. Previously, we proposed the second pyrethroid receptor, PyR2, at the I/II domain interface. However, whether DDT binds to both pyrethroid receptor sites remains unknown. Here, using computational docking of DDT into the Kv1.2-based mosquito sodium channel model, we predict that two DDT molecules can bind simultaneously within PyR1 and PyR2. The bulky trichloromethyl group of each DDT molecule fits snugly between four helices in the bent domain interface, whereas two p-chlorophenyl rings extend into two wings of the interface. Model-driven mutagenesis and electrophysiological analysis confirmed these propositions and revealed 10 previously unknown DDT-sensing residues within PyR1 and PyR2. Our study proposes a dual DDT-receptor model and provides a structural background for rational development of new insecticides. PMID:26637352

Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels.

PubMed

Du, Yuzhe; Nomura, Yoshiko; Zhorov, Boris S; Dong, Ke

2016-02-26

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoor residual spraying of DDT is still recommended for malaria control in Africa. Development of resistance to DDT and pyrethroids is a serious global obstacle for managing disease vectors. Mapping DDT binding sites is necessary for understanding mechanisms of resistance and modulation of sodium channels by structurally different ligands. The pioneering model of the housefly sodium channel visualized the first receptor for pyrethroids, PyR1, in the II/III domain interface and suggested that DDT binds within PyR1. Previously, we proposed the second pyrethroid receptor, PyR2, at the I/II domain interface. However, whether DDT binds to both pyrethroid receptor sites remains unknown. Here, using computational docking of DDT into the Kv1.2-based mosquito sodium channel model, we predict that two DDT molecules can bind simultaneously within PyR1 and PyR2. The bulky trichloromethyl group of each DDT molecule fits snugly between four helices in the bent domain interface, whereas two p-chlorophenyl rings extend into two wings of the interface. Model-driven mutagenesis and electrophysiological analysis confirmed these propositions and revealed 10 previously unknown DDT-sensing residues within PyR1 and PyR2. Our study proposes a dual DDT-receptor model and provides a structural background for rational development of new insecticides. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Beta oscillations define discrete perceptual cycles in the somatosensory domain.

PubMed

Baumgarten, Thomas J; Schnitzler, Alfons; Lange, Joachim

2015-09-29

Whether seeing a movie, listening to a song, or feeling a breeze on the skin, we coherently experience these stimuli as continuous, seamless percepts. However, there are rare perceptual phenomena that argue against continuous perception but, instead, suggest discrete processing of sensory input. Empirical evidence supporting such a discrete mechanism, however, remains scarce and comes entirely from the visual domain. Here, we demonstrate compelling evidence for discrete perceptual sampling in the somatosensory domain. Using magnetoencephalography (MEG) and a tactile temporal discrimination task in humans, we find that oscillatory alpha- and low beta-band (8-20 Hz) cycles in primary somatosensory cortex represent neurophysiological correlates of discrete perceptual cycles. Our results agree with several theoretical concepts of discrete perceptual sampling and empirical evidence of perceptual cycles in the visual domain. Critically, these results show that discrete perceptual cycles are not domain-specific, and thus restricted to the visual domain, but extend to the somatosensory domain.

Crystal structure of the motor domain of a class-I myosin

PubMed Central

Kollmar, Martin; Dürrwang, Ulrike; Kliche, Werner; Manstein, Dietmar J.; Kull, F.Jon

2002-01-01

The crystal structure of the motor domain of Dictyostelium discoideum myosin-IE, a monomeric unconventional myosin, was determined. The crystallographic asymmetric unit contains four independently resolved molecules, highlighting regions that undergo large conformational changes. Differences are particularly pronounced in the actin binding region and the converter domain. The changes in position of the converter domain reflect movements both parallel to and perpendicular to the actin axis. The orientation of the converter domain is ∼30° further up than in other myosin structures, indicating that MyoE can produce a larger power stroke by rotating its lever arm through a larger angle. The role of extended loops near the actin-binding site is discussed in the context of cellular localization. The core regions of the motor domain are similar, and the structure reveals how that core is stabilized in the absence of an N-terminal SH3-like domain. PMID:12032065

Finite difference time domain calculation of transients in antennas with nonlinear loads

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.; Kunz, Karl S.; Chamberlin, Kent

1991-01-01

In this paper transient fields for antennas with more general geometries are calculated directly using Finite Difference Time Domain methods. In each FDTD cell which contains a nonlinear load, a nonlinear equation is solved at each time step. As a test case the transient current in a long dipole antenna with a nonlinear load excited by a pulsed plane wave is computed using this approach. The results agree well with both calculated and measured results previously published. The approach given here extends the applicability of the FDTD method to problems involving scattering from targets including nonlinear loads and materials, and to coupling between antennas containing nonlinear loads. It may also be extended to propagation through nonlinear materials.

Preservation of protein clefts in comparative models.

PubMed

Piedra, David; Lois, Sergi; de la Cruz, Xavier

2008-01-16

Comparative, or homology, modelling of protein structures is the most widely used prediction method when the target protein has homologues of known structure. Given that the quality of a model may vary greatly, several studies have been devoted to identifying the factors that influence modelling results. These studies usually consider the protein as a whole, and only a few provide a separate discussion of the behaviour of biologically relevant features of the protein. Given the value of the latter for many applications, here we extended previous work by analysing the preservation of native protein clefts in homology models. We chose to examine clefts because of their role in protein function/structure, as they are usually the locus of protein-protein interactions, host the enzymes' active site, or, in the case of protein domains, can also be the locus of domain-domain interactions that lead to the structure of the whole protein. We studied how the largest cleft of a protein varies in comparative models. To this end, we analysed a set of 53507 homology models that cover the whole sequence identity range, with a special emphasis on medium and low similarities. More precisely we examined how cleft quality - measured using six complementary parameters related to both global shape and local atomic environment, depends on the sequence identity between target and template proteins. In addition to this general analysis, we also explored the impact of a number of factors on cleft quality, and found that the relationship between quality and sequence identity varies depending on cleft rank amongst the set of protein clefts (when ordered according to size), and number of aligned residues. We have examined cleft quality in homology models at a range of seq.id. levels. Our results provide a detailed view of how quality is affected by distinct parameters and thus may help the user of comparative modelling to determine the final quality and applicability of his/her cleft models. In addition, the large variability in model quality that we observed within each sequence bin, with good models present even at low sequence identities (between 20% and 30%), indicates that properly developed identification methods could be used to recover good cleft models in this sequence range.

The effects of global change upon United States air quality

NASA Astrophysics Data System (ADS)

Gonzalez-Abraham, R.; Avise, J.; Chung, S. H.; Lamb, B.; Salathé, E. P., Jr.; Nolte, C. G.; Loughlin, D.; Guenther, A.; Wiedinmyer, C.; Duhl, T.; Zhang, Y.; Streets, D. G.

2014-12-01

To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the US, we conducted a comprehensive modeling effort to evaluate explicitly the effects of changes in climate, biogenic emissions, land use, and global/regional anthropogenic emissions on ozone and PM2.5 concentrations and composition. Results from the ECHAM5 global climate model driven with the A1B emission scenario from the Intergovernmental Panel on Climate Change (IPCC) were downscaled using the Weather Research and Forecasting (WRF) model to provide regional meteorological fields. We developed air quality simulations using the Community Multiscale Air Quality Model (CMAQ) chemical transport model for two nested domains with 220 and 36 km horizontal grid cell resolution for a semi-hemispheric domain and a continental United States (US) domain, respectively. The semi-hemispheric domain was used to evaluate the impact of projected Asian emissions changes on US air quality. WRF meteorological fields were used to calculate current (2000s) and future (2050s) biogenic emissions using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). For the semi-hemispheric domain CMAQ simulations, present-day global emissions inventories were used and projected to the 2050s based on the IPCC A1B scenario. Regional anthropogenic emissions were obtained from the US Environmental Protection Agency National Emission Inventory 2002 (EPA NEI2002) and projected to the future using the MARKet ALlocation (MARKAL) energy system model assuming a business as usual scenario that extends current decade emission regulations through 2050. Our results suggest that daily maximum 8 h average ozone (DM8O) concentrations will increase in a range between 2 to 12 ppb across most of the continental US, with the highest increase in the South, Central, and Midwest regions of the US, due to increases in temperature, enhanced biogenic emissions, and changes in land use. The effects of these factors are only partially offset by reductions in DM8O associated with decreasing US anthropogenic emissions. Increases in PM2.5 levels between 2 and 4 μg m-3 in the Northeast, Southeast, and South regions are mostly a result of enhanced biogenic emissions and land use changes. Little change in PM2.5 in the Central, Northwest, and Southwest regions was found, even when PM precursors are reduced with regulatory curtailment. Changes in temperature, relative humidity, and boundary conditions shift the composition but do not alter overall PM2.5 mass concentrations.

Domain and Specification Models for Software Engineering

NASA Technical Reports Server (NTRS)

Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

1992-01-01

This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

First experience with the new .cern Top Level Domain

NASA Astrophysics Data System (ADS)

Alvarez, E.; Malo de Molina, M.; Salwerowicz, M.; Silva De Sousa, B.; Smith, T.; Wagner, A.

2017-10-01

In October 2015, CERN’s core website has been moved to a new address, http://home.cern, marking the launch of the brand new top-level domain .cern. In combination with a formal governance and registration policy, the IT infrastructure needed to be extended to accommodate the hosting of Web sites in this new top level domain. We will present the technical implementation in the framework of the CERN Web Services that allows to provide virtual hosting, a reverse proxy solution and that also includes the provisioning of SSL server certificates for secure communications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franović, Igor, E-mail: franovic@ipb.ac.rs; Todorović, Kristina; Burić, Nikola

We use the mean-field approach to analyze the collective dynamics in macroscopic networks of stochastic Fitzhugh-Nagumo units with delayed couplings. The conditions for validity of the two main approximations behind the model, called the Gaussian approximation and the Quasi-independence approximation, are examined. It is shown that the dynamics of the mean-field model may indicate in a self-consistent fashion the parameter domains where the Quasi-independence approximation fails. Apart from a network of globally coupled units, we also consider the paradigmatic setup of two interacting assemblies to demonstrate how our framework may be extended to hierarchical and modular networks. In both cases,more » the mean-field model can be used to qualitatively analyze the stability of the system, as well as the scenarios for the onset and the suppression of the collective mode. In quantitative terms, the mean-field model is capable of predicting the average oscillation frequency corresponding to the global variables of the exact system.« less

Effective description of domain wall strings

NASA Astrophysics Data System (ADS)

Rodrigues, Davi R.; Abanov, Ar.; Sinova, J.; Everschor-Sitte, K.

2018-04-01

The analysis of domain wall dynamics is often simplified to one-dimensional physics. For domain walls in thin films, more realistic approaches require the description as two-dimensional objects. This includes the study of vortices and curvatures along the domain walls as well as the influence of boundary effects. Here we provide a theory in terms of soft modes that allows us to analytically study the physics of extended domain walls and their stability. By considering irregularly shaped skyrmions as closed domain walls, we analyze their plasticity and compare their dynamics with those of circular skyrmions. Our theory directly provides an analytical description of the excitation modes of magnetic skyrmions, previously accessible only through sophisticated micromagnetic numerical calculations and spectral analysis. These analytical expressions provide the scaling behavior of the different physics on parameters that experiments can test.

Separation of non-stationary multi-source sound field based on the interpolated time-domain equivalent source method

NASA Astrophysics Data System (ADS)

Bi, Chuan-Xing; Geng, Lin; Zhang, Xiao-Zheng

2016-05-01

In the sound field with multiple non-stationary sources, the measured pressure is the sum of the pressures generated by all sources, and thus cannot be used directly for studying the vibration and sound radiation characteristics of every source alone. This paper proposes a separation model based on the interpolated time-domain equivalent source method (ITDESM) to separate the pressure field belonging to every source from the non-stationary multi-source sound field. In the proposed method, ITDESM is first extended to establish the relationship between the mixed time-dependent pressure and all the equivalent sources distributed on every source with known location and geometry information, and all the equivalent source strengths at each time step are solved by an iterative solving process; then, the corresponding equivalent source strengths of one interested source are used to calculate the pressure field generated by that source alone. Numerical simulation of two baffled circular pistons demonstrates that the proposed method can be effective in separating the non-stationary pressure generated by every source alone in both time and space domains. An experiment with two speakers in a semi-anechoic chamber further evidences the effectiveness of the proposed method.

A Variational Approach to Simultaneous Image Segmentation and Bias Correction.

PubMed

Zhang, Kaihua; Liu, Qingshan; Song, Huihui; Li, Xuelong

2015-08-01

This paper presents a novel variational approach for simultaneous estimation of bias field and segmentation of images with intensity inhomogeneity. We model intensity of inhomogeneous objects to be Gaussian distributed with different means and variances, and then introduce a sliding window to map the original image intensity onto another domain, where the intensity distribution of each object is still Gaussian but can be better separated. The means of the Gaussian distributions in the transformed domain can be adaptively estimated by multiplying the bias field with a piecewise constant signal within the sliding window. A maximum likelihood energy functional is then defined on each local region, which combines the bias field, the membership function of the object region, and the constant approximating the true signal from its corresponding object. The energy functional is then extended to the whole image domain by the Bayesian learning approach. An efficient iterative algorithm is proposed for energy minimization, via which the image segmentation and bias field correction are simultaneously achieved. Furthermore, the smoothness of the obtained optimal bias field is ensured by the normalized convolutions without extra cost. Experiments on real images demonstrated the superiority of the proposed algorithm to other state-of-the-art representative methods.

Exploring dangerous neighborhoods: Latent Semantic Analysis and computing beyond the bounds of the familiar

PubMed Central

Cohen, Trevor; Blatter, Brett; Patel, Vimla

2005-01-01

Certain applications require computer systems to approximate intended human meaning. This is achievable in constrained domains with a finite number of concepts. Areas such as psychiatry, however, draw on concepts from the world-at-large. A knowledge structure with broad scope is required to comprehend such domains. Latent Semantic Analysis (LSA) is an unsupervised corpus-based statistical method that derives quantitative estimates of the similarity between words and documents from their contextual usage statistics. The aim of this research was to evaluate the ability of LSA to derive meaningful associations between concepts relevant to the assessment of dangerousness in psychiatry. An expert reference model of dangerousness was used to guide the construction of a relevant corpus. Derived associations between words in the corpus were evaluated qualitatively. A similarity-based scoring function was used to assign dangerousness categories to discharge summaries. LSA was shown to derive intuitive relationships between concepts and correlated significantly better than random with human categorization of psychiatric discharge summaries according to dangerousness. The use of LSA to derive a simulated knowledge structure can extend the scope of computer systems beyond the boundaries of constrained conceptual domains. PMID:16779020

Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

PubMed

Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

2014-10-01

The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations. © 2014 Wiley Periodicals, Inc.

A compressive sensing based secure watermark detection and privacy preserving storage framework.

PubMed

Qia Wang; Wenjun Zeng; Jun Tian

2014-03-01

Privacy is a critical issue when the data owners outsource data storage or processing to a third party computing service, such as the cloud. In this paper, we identify a cloud computing application scenario that requires simultaneously performing secure watermark detection and privacy preserving multimedia data storage. We then propose a compressive sensing (CS)-based framework using secure multiparty computation (MPC) protocols to address such a requirement. In our framework, the multimedia data and secret watermark pattern are presented to the cloud for secure watermark detection in a CS domain to protect the privacy. During CS transformation, the privacy of the CS matrix and the watermark pattern is protected by the MPC protocols under the semi-honest security model. We derive the expected watermark detection performance in the CS domain, given the target image, watermark pattern, and the size of the CS matrix (but without the CS matrix itself). The correctness of the derived performance has been validated by our experiments. Our theoretical analysis and experimental results show that secure watermark detection in the CS domain is feasible. Our framework can also be extended to other collaborative secure signal processing and data-mining applications in the cloud.

Local dynamics and spatiotemporal chaos. The Kuramoto- Sivashinsky equation: A case study

NASA Astrophysics Data System (ADS)

Wittenberg, Ralf Werner

The nature of spatiotemporal chaos in extended continuous systems is not yet well-understood. In this thesis, a model partial differential equation, the Kuramoto- Sivashinsky (KS) equation ut+uxxxx+uxx+uux =0 on a large one-dimensional periodic domain, is studied analytically, numerically, and through modeling to obtain a more detailed understanding of the observed spatiotemporally complex dynamics. In particular, with the aid of a wavelet decomposition, the relevant dynamical interactions are shown to be localized in space and scale. Motivated by these results, and by the idea that the attractor on a large domain may be understood via attractors on smaller domains, a spatially localized low- dimensional model for a minimal chaotic box is proposed. A (de)stabilized extension of the KS equation has recently attracted increased interest; for this situation, dissipativity and analyticity areproven, and an explicit shock-like solution is constructed which sheds light on the difficulties in obtaining optimal bounds for the KS equation. For the usual KS equation, the spatiotemporally chaotic state is carefully characterized in real, Fourier and wavelet space. The wavelet decomposition provides good scale separation which isolates the three characteristic regions of the dynamics: large scales of slow Gaussian fluctuations, active scales containing localized interactions of coherent structures, and small scales. Space localization is shown through a comparison of various correlation lengths and a numerical experiment in which different modes are uncoupled to estimate a dynamic interaction length. A detailed picture of the contributions of different scales to the spatiotemporally complex dynamics is obtained via a Galerkin projection of the KS equation onto the wavelet basis, and an extensive series of numerical experiments in which different combinations of wavelet levels are eliminated or forced. These results, and a formalism to derive an effective equation for periodized subsystems externally forced from a larger system, motivate various models for spatially localized forced systems. There is convincing evidence that short periodized systems, internally forced at the largest scales, form a minimal model for the observed extensively chaotic dynamics in larger domains.

An adaptable parallel algorithm for the direct numerical simulation of incompressible turbulent flows using a Fourier spectral/hp element method and MPI virtual topologies

NASA Astrophysics Data System (ADS)

Bolis, A.; Cantwell, C. D.; Moxey, D.; Serson, D.; Sherwin, S. J.

2016-09-01

A hybrid parallelisation technique for distributed memory systems is investigated for a coupled Fourier-spectral/hp element discretisation of domains characterised by geometric homogeneity in one or more directions. The performance of the approach is mathematically modelled in terms of operation count and communication costs for identifying the most efficient parameter choices. The model is calibrated to target a specific hardware platform after which it is shown to accurately predict the performance in the hybrid regime. The method is applied to modelling turbulent flow using the incompressible Navier-Stokes equations in an axisymmetric pipe and square channel. The hybrid method extends the practical limitations of the discretisation, allowing greater parallelism and reduced wall times. Performance is shown to continue to scale when both parallelisation strategies are used.

Modelling human problem solving with data from an online game.

PubMed

Rach, Tim; Kirsch, Alexandra

2016-11-01

Since the beginning of cognitive science, researchers have tried to understand human strategies in order to develop efficient and adequate computational methods. In the domain of problem solving, the travelling salesperson problem has been used for the investigation and modelling of human solutions. We propose to extend this effort with an online game, in which instances of the travelling salesperson problem have to be solved in the context of a game experience. We report on our effort to design and run such a game, present the data contained in the resulting openly available data set and provide an outlook on the use of games in general for cognitive science research. In addition, we present three geometrical models mapping the starting point preferences in the problems presented in the game as the result of an evaluation of the data set.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Chunhua; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108; Lv, Dashuai

Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regionsmore » between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.« less

eVITAL: A Preliminary Taxonomy and Electronic Toolkit of Health-Related Habits and Lifestyle

PubMed Central

Salvador-Carulla, Luis; Olson Walsh, Carolyn; Alonso, Federico; Gómez, Rafael; de Teresa, Carlos; Cabo-Soler, José Ricardo; Cano, Antonio; Ruiz, Mencía

2012-01-01

Objectives. To create a preliminary taxonomy and related toolkit of health-related habits (HrH) following a person-centered approach with a focus on primary care. Methods. From 2003–2009, a working group (n = 6 physicians) defined the knowledge base, created a framing document, and selected evaluation tools using an iterative process. Multidisciplinary focus groups (n = 29 health professionals) revised the document and evaluation protocol and participated in a feasibility study and review of the model based on a demonstration study with 11 adult volunteers in Antequera, Spain. Results. The preliminary taxonomy contains 6 domains of HrH and 1 domain of additional health descriptors, 3 subdomains, 43 dimensions, and 141 subdimensions. The evaluation tool was completed by the 11 volunteers. The eVITAL toolkit contains history and examination items for 4 levels of engagement: self-assessment, basic primary care, extended primary care, and specialty care. There was positive feedback from the volunteers and experts, but concern about the length of the evaluation. Conclusions. We present the first taxonomy of HrH, which may aid the development of the new models of care such as the personal contextual factors of the International Classification of Functioning (ICF) and the positive and negative components of the multilevel person-centered integrative diagnosis model. PMID:22545016

Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity.

PubMed

Ahlberg, Ernst; Amberg, Alexander; Beilke, Lisa D; Bower, David; Cross, Kevin P; Custer, Laura; Ford, Kevin A; Van Gompel, Jacky; Harvey, James; Honma, Masamitsu; Jolly, Robert; Joossens, Elisabeth; Kemper, Raymond A; Kenyon, Michelle; Kruhlak, Naomi; Kuhnke, Lara; Leavitt, Penny; Naven, Russell; Neilan, Claire; Quigley, Donald P; Shuey, Dana; Spirkl, Hans-Peter; Stavitskaya, Lidiya; Teasdale, Andrew; White, Angela; Wichard, Joerg; Zwickl, Craig; Myatt, Glenn J

2016-06-01

Statistical-based and expert rule-based models built using public domain mutagenicity knowledge and data are routinely used for computational (Q)SAR assessments of pharmaceutical impurities in line with the approach recommended in the ICH M7 guideline. Knowledge from proprietary corporate mutagenicity databases could be used to increase the predictive performance for selected chemical classes as well as expand the applicability domain of these (Q)SAR models. This paper outlines a mechanism for sharing knowledge without the release of proprietary data. Primary aromatic amine mutagenicity was selected as a case study because this chemical class is often encountered in pharmaceutical impurity analysis and mutagenicity of aromatic amines is currently difficult to predict. As part of this analysis, a series of aromatic amine substructures were defined and the number of mutagenic and non-mutagenic examples for each chemical substructure calculated across a series of public and proprietary mutagenicity databases. This information was pooled across all sources to identify structural classes that activate or deactivate aromatic amine mutagenicity. This structure activity knowledge, in combination with newly released primary aromatic amine data, was incorporated into Leadscope's expert rule-based and statistical-based (Q)SAR models where increased predictive performance was demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagramming Transactive Building Business Cases: Using Principles of e3 Value to Document Valuation Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammerstrom, Donald J.; Makhmalbaf, Atefe; Marinovici, Maria C.

Energy management in buildings is becoming more transactive. Pacific Northwest National Laboratory and the U.S. Department of Energy Building Technologies Office recently defined innovative use cases wherein market-like mechanisms are used to manage energy within buildings, between buildings, and between buildings and third-party entities, such as power utilities. A next step toward defining a set of transactive use cases in the buildings domain is to carefully diagram the corresponding business cases to capture details of transactions among all stakeholders and their economic value propositions. The principles of e3-value diagramming are applied in this report toward creating business value diagrams. Thesemore » principles are extended to be consistent with Universal Modeling Language use-case diagrams. Example diagrams are presented for a subset of buildings-domain use cases that were introduced in an earlier Pacific Northwest National Laboratory report. The diagrams are intended to clearly represent an understanding of the transactions through which individual entities accumulate value in their respective use cases, and the diagrams should therefore support economic valuation studies. The report reviews some of the foundational principles of e3 value and includes authors’ insights concerning the formulation of these diagrams using Universal Modeling Language as a more systematic modeling approach.« less

Genome3D: a UK collaborative project to annotate genomic sequences with predicted 3D structures based on SCOP and CATH domains.

PubMed

Lewis, Tony E; Sillitoe, Ian; Andreeva, Antonina; Blundell, Tom L; Buchan, Daniel W A; Chothia, Cyrus; Cuff, Alison; Dana, Jose M; Filippis, Ioannis; Gough, Julian; Hunter, Sarah; Jones, David T; Kelley, Lawrence A; Kleywegt, Gerard J; Minneci, Federico; Mitchell, Alex; Murzin, Alexey G; Ochoa-Montaño, Bernardo; Rackham, Owen J L; Smith, James; Sternberg, Michael J E; Velankar, Sameer; Yeats, Corin; Orengo, Christine

2013-01-01

Genome3D, available at http://www.genome3d.eu, is a new collaborative project that integrates UK-based structural resources to provide a unique perspective on sequence-structure-function relationships. Leading structure prediction resources (DomSerf, FUGUE, Gene3D, pDomTHREADER, Phyre and SUPERFAMILY) provide annotations for UniProt sequences to indicate the locations of structural domains (structural annotations) and their 3D structures (structural models). Structural annotations and 3D model predictions are currently available for three model genomes (Homo sapiens, E. coli and baker's yeast), and the project will extend to other genomes in the near future. As these resources exploit different strategies for predicting structures, the main aim of Genome3D is to enable comparisons between all the resources so that biologists can see where predictions agree and are therefore more trusted. Furthermore, as these methods differ in whether they build their predictions using CATH or SCOP, Genome3D also contains the first official mapping between these two databases. This has identified pairs of similar superfamilies from the two resources at various degrees of consensus (532 bronze pairs, 527 silver pairs and 370 gold pairs).

Phosphorylation and calcium antagonistically tune myosin-binding protein C’s structure and function

PubMed Central

Previs, Michael J.; Mun, Ji Young; Michalek, Arthur J.; Previs, Samantha Beck; Gulick, James; Robbins, Jeffrey; Warshaw, David M.; Craig, Roger

2016-01-01

During each heartbeat, cardiac contractility results from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filaments to shorten cellular length. Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filament that appears to tune these mechanochemical interactions by its N-terminal domains transiently interacting with actin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding velocity. Both functional mechanisms are potentially further tunable by phosphorylation of an intrinsically disordered, extensible region of cMyBP-C’s N terminus, the M-domain. Using atomic force spectroscopy, electron microscopy, and mutant protein expression, we demonstrate that phosphorylation reduced the M-domain’s extensibility and shifted the conformation of the N-terminal domain from an extended structure to a compact configuration. In combination with motility assay data, these structural effects of M-domain phosphorylation suggest a mechanism for diminishing the functional potency of individual cMyBP-C molecules. Interestingly, we found that calcium levels necessary to maximally activate the thin filament mitigated the structural effects of phosphorylation by increasing M-domain extensibility and shifting the phosphorylated N-terminal fragments back to the extended state, as if unphosphorylated. Functionally, the addition of calcium to the motility assays ablated the impact of phosphorylation on maximal sliding velocities, fully restoring cMyBP-C’s inhibitory capacity. We conclude that M-domain phosphorylation may have its greatest effect on tuning cMyBP-C’s calcium-sensitization of thin filaments at the low calcium levels between contractions. Importantly, calcium levels at the peak of contraction would allow cMyBP-C to remain a potent contractile modulator, regardless of cMyBP-C’s phosphorylation state. PMID:26908872

Identifying appropriate reference data models for comparative effectiveness research (CER) studies based on data from clinical information systems.

PubMed

Ogunyemi, Omolola I; Meeker, Daniella; Kim, Hyeon-Eui; Ashish, Naveen; Farzaneh, Seena; Boxwala, Aziz

2013-08-01

The need for a common format for electronic exchange of clinical data prompted federal endorsement of applicable standards. However, despite obvious similarities, a consensus standard has not yet been selected in the comparative effectiveness research (CER) community. Using qualitative metrics for data retrieval and information loss across a variety of CER topic areas, we compare several existing models from a representative sample of organizations associated with clinical research: the Observational Medical Outcomes Partnership (OMOP), Biomedical Research Integrated Domain Group, the Clinical Data Interchange Standards Consortium, and the US Food and Drug Administration. While the models examined captured a majority of the data elements that are useful for CER studies, data elements related to insurance benefit design and plans were most detailed in OMOP's CDM version 4.0. Standardized vocabularies that facilitate semantic interoperability were included in the OMOP and US Food and Drug Administration Mini-Sentinel data models, but are left to the discretion of the end-user in Biomedical Research Integrated Domain Group and Analysis Data Model, limiting reuse opportunities. Among the challenges we encountered was the need to model data specific to a local setting. This was handled by extending the standard data models. We found that the Common Data Model from the OMOP met the broadest complement of CER objectives. Minimal information loss occurred in mapping data from institution-specific data warehouses onto the data models from the standards we assessed. However, to support certain scenarios, we found a need to enhance existing data dictionaries with local, institution-specific information.

Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

PubMed

Lingenhöhl, K; Finch, D M

1991-01-01

We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would support divergent propagation of their activity.

Immersed Boundary Methods for High-Resolution Simulation of Atmospheric Boundary-Layer Flow Over Complex Terrain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundquist, K A

Mesoscale models, such as the Weather Research and Forecasting (WRF) model, are increasingly used for high resolution simulations, particularly in complex terrain, but errors associated with terrain-following coordinates degrade the accuracy of the solution. Use of an alternative Cartesian gridding technique, known as an immersed boundary method (IBM), alleviates coordinate transformation errors and eliminates restrictions on terrain slope which currently limit mesoscale models to slowly varying terrain. In this dissertation, an immersed boundary method is developed for use in numerical weather prediction. Use of the method facilitates explicit resolution of complex terrain, even urban terrain, in the WRF mesoscale model.more » First, the errors that arise in the WRF model when complex terrain is present are presented. This is accomplished using a scalar advection test case, and comparing the numerical solution to the analytical solution. Results are presented for different orders of advection schemes, grid resolutions and aspect ratios, as well as various degrees of terrain slope. For comparison, results from the same simulation are presented using the IBM. Both two-dimensional and three-dimensional immersed boundary methods are then described, along with details that are specific to the implementation of IBM in the WRF code. Our IBM is capable of imposing both Dirichlet and Neumann boundary conditions. Additionally, a method for coupling atmospheric physics parameterizations at the immersed boundary is presented, making IB methods much more functional in the context of numerical weather prediction models. The two-dimensional IB method is verified through comparisons of solutions for gentle terrain slopes when using IBM and terrain-following grids. The canonical case of flow over a Witch of Agnesi hill provides validation of the basic no-slip and zero gradient boundary conditions. Specified diurnal heating in a valley, producing anabatic winds, is used to validate the use of flux (non-zero) boundary conditions. This anabatic flow set-up is further coupled to atmospheric physics parameterizations, which calculate surface fluxes, demonstrating that the IBM can be coupled to various land-surface parameterizations in atmospheric models. Additionally, the IB method is extended to three dimensions, using both trilinear and inverse distance weighted interpolations. Results are presented for geostrophic flow over a three-dimensional hill. It is found that while the IB method using trilinear interpolation works well for simple three-dimensional geometries, a more flexible and robust method is needed for extremely complex geometries, as found in three-dimensional urban environments. A second, more flexible, immersed boundary method is devised using inverse distance weighting, and results are compared to the first IBM approach. Additionally, the functionality to nest a domain with resolved complex geometry inside of a parent domain without resolved complex geometry is described. The new IBM approach is used to model urban terrain from Oklahoma City in a one-way nested configuration, where lateral boundary conditions are provided by the parent domain. Finally, the IB method is extended to include wall model parameterizations for rough surfaces. Two possible implementations are presented, one which uses the log law to reconstruct velocities exterior to the solid domain, and one which reconstructs shear stress at the immersed boundary, rather than velocity. These methods are tested on the three-dimensional canonical case of neutral atmospheric boundary layer flow over flat terrain.« less

Application of CRAFT (complete reduction to amplitude frequency table) in nonuniformly sampled (NUS) 2D NMR data processing.

PubMed

Krishnamurthy, Krish; Hari, Natarajan

2017-09-15

The recently published CRAFT (complete reduction to amplitude frequency table) technique converts the raw FID data (i.e., time domain data) into a table of frequencies, amplitudes, decay rate constants, and phases. It offers an alternate approach to decimate time-domain data, with minimal preprocessing step. It has been shown that application of CRAFT technique to process the t 1 dimension of the 2D data significantly improved the detectable resolution by its ability to analyze without the use of ubiquitous apodization of extensively zero-filled data. It was noted earlier that CRAFT did not resolve sinusoids that were not already resolvable in time-domain (i.e., t 1 max dependent resolution). We present a combined NUS-IST-CRAFT approach wherein the NUS acquisition technique (sparse sampling technique) increases the intrinsic resolution in time-domain (by increasing t 1 max), IST fills the gap in the sparse sampling, and CRAFT processing extracts the information without loss due to any severe apodization. NUS and CRAFT are thus complementary techniques to improve intrinsic and usable resolution. We show that significant improvement can be achieved with this combination over conventional NUS-IST processing. With reasonable sensitivity, the models can be extended to significantly higher t 1 max to generate an indirect-DEPT spectrum that rivals the direct observe counterpart. Copyright © 2017 John Wiley & Sons, Ltd.

Prion-specific Hsp40 function: The role of the auxilin homolog Swa2

PubMed Central

Oliver, Emily E.; Troisi, Elizabeth M.; Hines, Justin K.

2017-01-01

ABSTRACT Yeast prions are protein-based genetic elements that propagate through cell populations via cytosolic transfer from mother to daughter cell. Molecular chaperone proteins including Hsp70, the Hsp40/J-protein Sis1, and Hsp104 are required for continued prion propagation, however the specific requirements of chaperone proteins differ for various prions. We recently reported that Swa2, the yeast homolog of the mammalian protein auxilin, is specifically required for the propagation of the prion [URE3].1 [URE3] propagation requires both a functional J-domain and the tetratricopeptide repeat (TPR) domain of Swa2, but does not require Swa2 clathrin binding. We concluded that the TPR domain determines the specificity of the genetic interaction between Swa2 and [URE3], and that this domain likely interacts with one or more proteins with a C-terminal EEVD motif. Here we extend that analysis to incorporate additional data that supports this hypothesis. We also present new data eliminating Hsp104 as the relevant Swa2 binding partner and discuss our findings in the context of other recent work involving Hsp90. Based on these findings, we propose a new model for Swa2's involvement in [URE3] propagation in which Swa2 and Hsp90 mediate the formation of a multi-protein complex that increases the number of sites available for Hsp104 disaggregation. PMID:28574745

Kernel Manifold Alignment for Domain Adaptation.

PubMed

Tuia, Devis; Camps-Valls, Gustau

2016-01-01

The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain-specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across-domains and data synthesis. To authors' knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational efficiency, and discuss the generalization performance of KEMA under Rademacher principles of stability. Aligning multimodal data with KEMA reports outstanding benefits when used as a data pre-conditioner step in the standard data analysis processing chain. KEMA exhibits very good performance over competing methods in synthetic controlled examples, visual object recognition and recognition of facial expressions tasks. KEMA is especially well-suited to deal with high-dimensional problems, such as images and videos, and under complicated distortions, twists and warpings of the data manifolds. A fully functional toolbox is available at https://github.com/dtuia/KEMA.git.

Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

NASA Astrophysics Data System (ADS)

Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

2016-07-01

Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sensoy, Ozge; Weinstein, Harel

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of themore » membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Altogether, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling.« less