Identifying interactions between chemical entities in biomedical text.

PubMed

Lamurias, Andre; Ferreira, João D; Couto, Francisco M

2014-12-01

Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, "Identifying Interactions between Chemical Entities" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to stateof- the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice.

A biological approach to assembling tissue modules through endothelial capillary network formation.

PubMed

Riesberg, Jeremiah J; Shen, Wei

2015-09-01

To create functional tissues having complex structures, bottom-up approaches to assembling small tissue modules into larger constructs have been emerging. Most of these approaches are based on chemical reactions or physical interactions at the interface between tissue modules. Here we report a biological assembly approach to integrate small tissue modules through endothelial capillary network formation. When adjacent tissue modules contain appropriate extracellular matrix materials and cell types that support robust endothelial capillary network formation, capillary tubules form and grow across the interface, resulting in assembly of the modules into a single, larger construct. It was shown that capillary networks formed in modules of dense fibrin gels seeded with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs); adjacent modules were firmly assembled into an integrated construct having a strain to failure of 117 ± 26%, a tensile strength of 2208 ± 83 Pa and a Young's modulus of 2548 ± 574 Pa. Under the same culture conditions, capillary networks were absent in modules of dense fibrin gels seeded with either HUVECs or MSCs alone; adjacent modules disconnected even when handled gently. This biological assembly approach eliminates the need for chemical reactions or physical interactions and their associated limitations. In addition, the integrated constructs are prevascularized, and therefore this bottom-up assembly approach may also help address the issue of vascularization, another key challenge in tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

Interactive design and analysis of future large spacecraft concepts

NASA Technical Reports Server (NTRS)

Garrett, L. B.

1981-01-01

An interactive computer aided design program used to perform systems level design and analysis of large spacecraft concepts is presented. Emphasis is on rapid design, analysis of integrated spacecraft, and automatic spacecraft modeling for lattice structures. Capabilities and performance of multidiscipline applications modules, the executive and data management software, and graphics display features are reviewed. A single user at an interactive terminal create, design, analyze, and conduct parametric studies of Earth orbiting spacecraft with relative ease. Data generated in the design, analysis, and performance evaluation of an Earth-orbiting large diameter antenna satellite are used to illustrate current capabilities. Computer run time statistics for the individual modules quantify the speed at which modeling, analysis, and design evaluation of integrated spacecraft concepts is accomplished in a user interactive computing environment.

An integrative approach to inferring biologically meaningful gene modules

PubMed Central

2011-01-01

Background The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association. Results We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. Conclusions The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level. PMID:21791051

Investigation of direct integrated optics modulators. [applicable to data preprocessors

NASA Technical Reports Server (NTRS)

Batchman, T. E.

1980-01-01

Direct modulation techniques applicable to integrated optics data preprocessors were investigated. Several methods of modulating a coherent optical beam by interaction with an incoherent beam were studied. It was decided to investigate photon induced conductivity changes in thin semiconductor cladding layers on optical waveguides. Preliminary calculations indicate significant changes can be produced in the phase shift in a propagating wave when the conductivity is changed by ten percent or more. Experimental devices to verify these predicted phase changes and experiments designed to prove the concept are described.

Naver: a PC-cluster-based VR system

NASA Astrophysics Data System (ADS)

Park, ChangHoon; Ko, HeeDong; Kim, TaiYun

2003-04-01

In this paper, we present a new framework NAVER for virtual reality application. The NAVER is based on a cluster of low-cost personal computers. The goal of NAVER is to provide flexible, extensible, scalable and re-configurable framework for the virtual environments defined as the integration of 3D virtual space and external modules. External modules are various input or output devices and applications on the remote hosts. From the view of system, personal computers are divided into three servers according to its specific functions: Render Server, Device Server and Control Server. While Device Server contains external modules requiring event-based communication for the integration, Control Server contains external modules requiring synchronous communication every frame. And, the Render Server consists of 5 managers: Scenario Manager, Event Manager, Command Manager, Interaction Manager and Sync Manager. These managers support the declaration and operation of virtual environment and the integration with external modules on remote servers.

FIBER AND INTEGRATED OPTICS: Radio-frequency electrooptic modulation in optical fibers

NASA Astrophysics Data System (ADS)

Bulyuk, A. N.

1992-10-01

The electrooptic interaction in single-mode optical fibers with both linear and circular birefringe is analyzed. In most cases, a large interaction length imposes a limit on the modulation frequency. A circular birefringence in an optical fiber may lead to an effective coupling of polarization normal modes if a phase-matching condition is satisfied. Through an appropriate choice of polarization states of the light at the entrance and exit of the device, one can achieve a polarization modulation or a frequency shift of the light. There are possible applications in rf polarization modulators, devices for shifting the frequency of light, and detectors of electromagnetic fields.

Low-power nanophotonics: material and device technology

NASA Astrophysics Data System (ADS)

Thylén, Lars; Holmstrom, Petter; Wosinski, Lech; Lourdudoss, Sebastian

2013-05-01

Development in photonics for communications and interconnects pose increasing requirements on reduction of footprint, power dissipation and cost, as well as increased bandwidth. Nanophotonics integrated photonics has been viewed as a solution to this, capitalizing on development in nanotechnology and an increased understanding of light matter interaction on the nanoscale. The latter can be exemplified by plasmonics and low dimensional semiconductors such as quantum dots (QDs). In this scenario the development of improved electrooptic materials is of great importance, the electrooptic polymers being an example, since they potentially offer superior properties for optical phase modulators in terms of power and integratability. Phase modulators are essential for e.g. the rapidly developing advanced modulation formats, since phase modulation basically can generate any type of modulation. The electrooptic polymers, in combination with plasmonics nanoparticle array waveguides or nanostructured hybrid plasmonic media can give extremely compact and low power dissipation modulators. Low-dimensional semiconductors, e.g. in the shape of QDs, can be employed for modulation or switching functions, offering possibilities for scaling to 2 or 3 dimensions for advanced switching functions. In both the high field confinement plasmonics and QDs, the nanosizing is due to nearfield interactions, albeit being of different physical origin in the two cases. Epitaxial integration of III-V structures on Si plays an important role in developing high-performance light sources on silicon, eventually integrated with silicon electronics. A brief remark on all-optical vs. electronically controlled optical switching systems is also given.

Modulational instability and higher-order rogue waves with parameters modulation in a coupled integrable AB system via the generalized Darboux transformation.

PubMed

Wen, Xiao-Yong; Yan, Zhenya

2015-12-01

We study higher-order rogue wave (RW) solutions of the coupled integrable dispersive AB system (also called Pedlosky system), which describes the evolution of wave-packets in a marginally stable or unstable baroclinic shear flow in geophysical fluids. We propose its continuous-wave (CW) solutions and existent conditions for their modulation instability to form the rogue waves. A new generalized N-fold Darboux transformation (DT) is proposed in terms of the Taylor series expansion for the spectral parameter in the Darboux matrix and its limit procedure and applied to the CW solutions to generate multi-rogue wave solutions of the coupled AB system, which satisfy the general compatibility condition. The dynamical behaviors of these higher-order rogue wave solutions demonstrate both strong and weak interactions by modulating parameters, in which some weak interactions can generate the abundant triangle, pentagon structures, etc. Particularly, the trajectories of motion of peaks and depressions of profiles of the first-order RWs are explicitly analyzed. The generalized DT method used in this paper can be extended to other nonlinear integrable systems. These results may be useful for understanding the corresponding rogue-wave phenomena in fluid mechanics and related fields.

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

PubMed Central

Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

2013-01-01

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response. PMID:23658624

Design of an Agent-Based Model to Examine Population-Environment Interactions in Nang Rong District, Thailand.

PubMed

Walsh, Stephen J; Malanson, George P; Entwisle, Barbara; Rindfuss, Ronald R; Mucha, Peter J; Heumann, Benjamin W; McDaniel, Philip M; Frizzelle, Brian G; Verdery, Ashton M; Williams, Nathalie; Xiaozheng, Yao; Ding, Deng

2013-05-01

The design of an Agent-Based Model (ABM) is described that integrates Social and Land Use Modules to examine population-environment interactions in a former agricultural frontier in Northeastern Thailand. The ABM is used to assess household income and wealth derived from agricultural production of lowland, rain-fed paddy rice and upland field crops in Nang Rong District as well as remittances returned to the household from family migrants who are engaged in off-farm employment in urban destinations. The ABM is supported by a longitudinal social survey of nearly 10,000 households, a deep satellite image time-series of land use change trajectories, multi-thematic social and ecological data organized within a GIS, and a suite of software modules that integrate data derived from an agricultural cropping system model (DSSAT - Decision Support for Agrotechnology Transfer) and a land suitability model (MAXENT - Maximum Entropy), in addition to multi-dimensional demographic survey data of individuals and households. The primary modules of the ABM are the Initialization Module, Migration Module, Assets Module, Land Suitability Module, Crop Yield Module, Fertilizer Module, and the Land Use Change Decision Module. The architecture of the ABM is described relative to module function and connectivity through uni-directional or bi-directional links. In general, the Social Modules simulate changes in human population and social networks, as well as changes in population migration and household assets, whereas the Land Use Modules simulate changes in land use types, land suitability, and crop yields. We emphasize the description of the Land Use Modules - the algorithms and interactions between the modules are described relative to the project goals of assessing household income and wealth relative to shifts in land use patterns, household demographics, population migration, social networks, and agricultural activities that collectively occur within a marginalized environment that is subjected to a suite of endogenous and exogenous dynamics.

Design of an Agent-Based Model to Examine Population-Environment Interactions in Nang Rong District, Thailand

PubMed Central

Walsh, Stephen J.; Malanson, George P.; Entwisle, Barbara; Rindfuss, Ronald R.; Mucha, Peter J.; Heumann, Benjamin W.; McDaniel, Philip M.; Frizzelle, Brian G.; Verdery, Ashton M.; Williams, Nathalie; Xiaozheng, Yao; Ding, Deng

2013-01-01

The design of an Agent-Based Model (ABM) is described that integrates Social and Land Use Modules to examine population-environment interactions in a former agricultural frontier in Northeastern Thailand. The ABM is used to assess household income and wealth derived from agricultural production of lowland, rain-fed paddy rice and upland field crops in Nang Rong District as well as remittances returned to the household from family migrants who are engaged in off-farm employment in urban destinations. The ABM is supported by a longitudinal social survey of nearly 10,000 households, a deep satellite image time-series of land use change trajectories, multi-thematic social and ecological data organized within a GIS, and a suite of software modules that integrate data derived from an agricultural cropping system model (DSSAT – Decision Support for Agrotechnology Transfer) and a land suitability model (MAXENT – Maximum Entropy), in addition to multi-dimensional demographic survey data of individuals and households. The primary modules of the ABM are the Initialization Module, Migration Module, Assets Module, Land Suitability Module, Crop Yield Module, Fertilizer Module, and the Land Use Change Decision Module. The architecture of the ABM is described relative to module function and connectivity through uni-directional or bi-directional links. In general, the Social Modules simulate changes in human population and social networks, as well as changes in population migration and household assets, whereas the Land Use Modules simulate changes in land use types, land suitability, and crop yields. We emphasize the description of the Land Use Modules – the algorithms and interactions between the modules are described relative to the project goals of assessing household income and wealth relative to shifts in land use patterns, household demographics, population migration, social networks, and agricultural activities that collectively occur within a marginalized environment that is subjected to a suite of endogenous and exogenous dynamics. PMID:24277975

Integrating the Learning of Mathematics and Science Using Interactive Teaching and Learning Strategies

NASA Astrophysics Data System (ADS)

Holmes, Mark H.

2006-10-01

To help students grasp the intimate connections that exist between mathematics and its applications in other disciplines a library of interactive learning modules was developed. This library covers the mathematical areas normally studied by undergraduate students and is used in science courses at all levels. Moreover, the library is designed not just to provide critical connections across disciplines but to also provide longitudinal subject reinforcement as students progress in their studies. In the process of developing the modules a complete editing and publishing system was constructed that is optimized for automated maintenance and upgradeability of materials. The result is a single integrated production system for web-based educational materials. Included in this is a rigorous assessment program, involving both internal and external evaluations of each module. As will be seen, the formative evaluation obtained during the development of the library resulted in the modules successfully bridging multiple disciplines and breaking down the disciplinary barriers commonly found in their math and non-math courses.

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Miscellaneous.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and miscellaneous lessons on drug use prevention for integration into an existing seventh-grade middle school curriculum. The module, based on a type of interactive learning called infusion learning contains seven lessons each providing…

Towards the Integration of Niche and Network Theories.

PubMed

Godoy, Oscar; Bartomeus, Ignasi; Rohr, Rudolf P; Saavedra, Serguei

2018-04-01

The quest for understanding how species interactions modulate diversity has progressed by theoretical and empirical advances following niche and network theories. Yet, niche studies have been limited to describe coexistence within tropic levels despite incorporating information about multi-trophic interactions. Network approaches could address this limitation, but they have ignored the structure of species interactions within trophic levels. Here we call for the integration of niche and network theories to reach new frontiers of knowledge exploring how interactions within and across trophic levels promote species coexistence. This integration is possible due to the strong parallelisms in the historical development, ecological concepts, and associated mathematical tools of both theories. We provide a guideline to integrate this framework with observational and experimental studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor.

PubMed

Hedger, George; Shorthouse, David; Koldsø, Heidi; Sansom, Mark S P

2016-08-25

Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. -40 to -4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins.

Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor

PubMed Central

2016-01-01

Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. −40 to −4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins. PMID:27109430

Spacecraft Orbit Design and Analysis (SODA), version 1.0 user's guide

NASA Technical Reports Server (NTRS)

Stallcup, Scott S.; Davis, John S.

1989-01-01

The Spacecraft Orbit Design and Analysis (SODA) computer program, Version 1.0 is described. SODA is a spaceflight mission planning system which consists of five program modules integrated around a common database and user interface. SODA runs on a VAX/VMS computer with an EVANS & SUTHERLAND PS300 graphics workstation. BOEING RIM-Version 7 relational database management system performs transparent database services. In the current version three program modules produce an interactive three dimensional (3D) animation of one or more satellites in planetary orbit. Satellite visibility and sensor coverage capabilities are also provided. One module produces an interactive 3D animation of the solar system. Another module calculates cumulative satellite sensor coverage and revisit time for one or more satellites. Currently Earth, Moon, and Mars systems are supported for all modules except the solar system module.

Spacecraft Orbit Design and Analysis (SODA). Version 2.0: User's guide

NASA Technical Reports Server (NTRS)

Stallcup, Scott S.; Davis, John S.; Zsoldos, Jeffrey S.

1991-01-01

The Spacecraft Orbit Design and Analysis (SODA) computer program, Version 2.0, is discussed. SODA is a spaceflight mission planning system that consists of six program modules integrated around a common database and user interface. SODA runs on a VAX/VMS computer with an Evans and Sutherland PS300 graphics workstation. In the current version, three program modules produce an interactive three dimensional animation of one or more satellites in planetary orbit. Satellite visibility and sensor coverage capabilities are also provided. Circular and rectangular, off nadir, fixed and scanning sensors are supported. One module produces an interactive three dimensional animation of the solar system. Another module calculates cumulative satellite sensor coverage and revisit time for one or more satellites. Currently, Earth, Moon, and Mars systems are supported for all modules except the solar system module.

Systems and methods for knowledge discovery in spatial data

DOEpatents

Obradovic, Zoran; Fiez, Timothy E.; Vucetic, Slobodan; Lazarevic, Aleksandar; Pokrajac, Dragoljub; Hoskinson, Reed L.

2005-03-08

Systems and methods are provided for knowledge discovery in spatial data as well as to systems and methods for optimizing recipes used in spatial environments such as may be found in precision agriculture. A spatial data analysis and modeling module is provided which allows users to interactively and flexibly analyze and mine spatial data. The spatial data analysis and modeling module applies spatial data mining algorithms through a number of steps. The data loading and generation module obtains or generates spatial data and allows for basic partitioning. The inspection module provides basic statistical analysis. The preprocessing module smoothes and cleans the data and allows for basic manipulation of the data. The partitioning module provides for more advanced data partitioning. The prediction module applies regression and classification algorithms on the spatial data. The integration module enhances prediction methods by combining and integrating models. The recommendation module provides the user with site-specific recommendations as to how to optimize a recipe for a spatial environment such as a fertilizer recipe for an agricultural field.

Integrative Analysis of GWASs, Human Protein Interaction, and Gene Expression Identified Gene Modules Associated With BMDs

PubMed Central

He, Hao; Zhang, Lei; Li, Jian; Wang, Yu-Ping; Zhang, Ji-Gang; Shen, Jie; Guo, Yan-Fang

2014-01-01

Context: To date, few systems genetics studies in the bone field have been performed. We designed our study from a systems-level perspective by integrating genome-wide association studies (GWASs), human protein-protein interaction (PPI) network, and gene expression to identify gene modules contributing to osteoporosis risk. Methods: First we searched for modules significantly enriched with bone mineral density (BMD)-associated genes in human PPI network by using 2 large meta-analysis GWAS datasets through a dense module search algorithm. One included 7 individual GWAS samples (Meta7). The other was from the Genetic Factors for Osteoporosis Consortium (GEFOS2). One was assigned as a discovery dataset and the other as an evaluation dataset, and vice versa. Results: In total, 42 modules and 129 modules were identified significantly in both Meta7 and GEFOS2 datasets for femoral neck and spine BMD, respectively. There were 3340 modules identified for hip BMD only in Meta7. As candidate modules, they were assessed for the biological relevance to BMD by gene set enrichment analysis in 2 expression profiles generated from circulating monocytes in subjects with low versus high BMD values. Interestingly, there were 2 modules significantly enriched in monocytes from the low BMD group in both gene expression datasets (nominal P value <.05). Two modules had 16 nonredundant genes. Functional enrichment analysis revealed that both modules were enriched for genes involved in Wnt receptor signaling and osteoblast differentiation. Conclusion: We highlighted 2 modules and novel genes playing important roles in the regulation of bone mass, providing important clues for therapeutic approaches for osteoporosis. PMID:25119315

Advanced Artificial Intelligence Technology Testbed

NASA Technical Reports Server (NTRS)

Anken, Craig S.

1993-01-01

The Advanced Artificial Intelligence Technology Testbed (AAITT) is a laboratory testbed for the design, analysis, integration, evaluation, and exercising of large-scale, complex, software systems, composed of both knowledge-based and conventional components. The AAITT assists its users in the following ways: configuring various problem-solving application suites; observing and measuring the behavior of these applications and the interactions between their constituent modules; gathering and analyzing statistics about the occurrence of key events; and flexibly and quickly altering the interaction of modules within the applications for further study.

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Mathematics.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven in "Infusion Project", offers information and lessons on drug use prevention for integration into an existing seventh-grade middle school mathematics curriculum. The module, based on a type of interactive learning called infusion learning, contains eight lessons each providing objectives, a list of…

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Health.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven in Infusion Project, offers information and lessons on drug use prevention for integration into an existing seventh grade middle school health curriculum. The module, based on a type of interactive learning called infusion learning, contains 10 lessons each providing objectives, a list of resource materials,…

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Science.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and lessons on drug use prevention for integration into an existing seventh-grade middle school science curriculum. The module, based on a type of interactive learning called infusion learning, contains 12 lessons, each providing objectives, a…

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Geography.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven in the "Infusion Project," offers information and lessons on drug use prevention for integration into an existing seventh-grade middle school geography curriculum. The module, based on a type of interactive learning called infusion learning, contains 13 lessons each providing objectives, a list of…

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Language Arts.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven in Infusion Project, offers information and lessons on drug use prevention for integration into an existing seventh-grade middle school language arts curriculum. The module, based on a type of interactive learning called infusion learning, contains 18 lessons each providing objectives, a list of resource…

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Exceptional Education.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and lessons on drug use prevention for integration into an existing seventh-grade exceptional education middle school curriculum for social skills, mathematics, science and language arts. The module, based on a type of interactive learning called…

SOCRAT Platform Design: A Web Architecture for Interactive Visual Analytics Applications

PubMed Central

Kalinin, Alexandr A.; Palanimalai, Selvam; Dinov, Ivo D.

2018-01-01

The modern web is a successful platform for large scale interactive web applications, including visualizations. However, there are no established design principles for building complex visual analytics (VA) web applications that could efficiently integrate visualizations with data management, computational transformation, hypothesis testing, and knowledge discovery. This imposes a time-consuming design and development process on many researchers and developers. To address these challenges, we consider the design requirements for the development of a module-based VA system architecture, adopting existing practices of large scale web application development. We present the preliminary design and implementation of an open-source platform for Statistics Online Computational Resource Analytical Toolbox (SOCRAT). This platform defines: (1) a specification for an architecture for building VA applications with multi-level modularity, and (2) methods for optimizing module interaction, re-usage, and extension. To demonstrate how this platform can be used to integrate a number of data management, interactive visualization, and analysis tools, we implement an example application for simple VA tasks including raw data input and representation, interactive visualization and analysis. PMID:29630069

SOCRAT Platform Design: A Web Architecture for Interactive Visual Analytics Applications.

PubMed

Kalinin, Alexandr A; Palanimalai, Selvam; Dinov, Ivo D

2017-04-01

The modern web is a successful platform for large scale interactive web applications, including visualizations. However, there are no established design principles for building complex visual analytics (VA) web applications that could efficiently integrate visualizations with data management, computational transformation, hypothesis testing, and knowledge discovery. This imposes a time-consuming design and development process on many researchers and developers. To address these challenges, we consider the design requirements for the development of a module-based VA system architecture, adopting existing practices of large scale web application development. We present the preliminary design and implementation of an open-source platform for Statistics Online Computational Resource Analytical Toolbox (SOCRAT). This platform defines: (1) a specification for an architecture for building VA applications with multi-level modularity, and (2) methods for optimizing module interaction, re-usage, and extension. To demonstrate how this platform can be used to integrate a number of data management, interactive visualization, and analysis tools, we implement an example application for simple VA tasks including raw data input and representation, interactive visualization and analysis.

Titin Based Viscosity in Ventricular Physiology: An Integrative Investigation of PEVK-Actin Interactions

PubMed Central

Chung, Charles S; Methawasin, Methajit; Nelson, O Lynne; Radke, Michael H; Hidalgo, Carlos G; Gotthardt, Michael; Granzier, Henk L

2011-01-01

Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In-vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in-vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in-vivo via an integrative physiological study on a unique PEVK-knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30–40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in-vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in-vivo and shows that PEVK-actin interactions are an important physiological source of viscosity. PMID:21708170

Discovering perturbation of modular structure in HIV progression by integrating multiple data sources through non-negative matrix factorization.

PubMed

Ray, Sumanta; Maulik, Ujjwal

2016-12-20

Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified metamodules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

Effectiveness of a comprehensive integrated module using interactive lectures and workshops in understanding and knowledge retention about infant feeding practice in fifth year medical students: a quasi-experimental study.

PubMed

Sjarif, Damayanti Rusli; Yuliarti, Klara; Wahyuni, Luh Karunia; Wiguna, Tjhin; Prawitasari, Titis; Devaera, Yoga; Triyuniati, Henni Wahyu; Afriansyah, Andika

2016-08-18

Sixty percent of the 10.9 million under-5 deaths every year are related to malnutrition. More than two thirds of malnutrition is caused by inappropriate infant feeding practice. Only 35 % of mothers worldwide provide 4 months of exclusive breast-feeding, while complementary feeding is often untimely, nutritionally inadequate, hygienically poor, and improperly delivered. The existing pediatric nutrition module in our institution does not include proper delivery of food that involves oral-motor skills and feeding behavior. To scale up the knowledge and skill of medical students regarding evidence-based infant feeding practice, we designed a new module composed of comprehensive and integrated lectures with additional multidisciplinary lectures on oral-motor skill development and feeding behavior. A quasi-experimental study was conducted to evaluate the efficacy of the new module compared to the previous module. Fifth year medical students of Universitas Indonesia were divided into intervention and control groups. The control group received lectures and a paper-based workshop. The intervention group received comprehensive and integrated interactive lectures with additional multidisciplinary lectures on oral-motor skill development and behavioral approaches to feeding problems. A hands-on workshop using real cases shown on recorded video and role-play sessions was also presented to the intervention group. A pre-/post-test, 3-month retention test, and Observed Structured Clinical Examination (OSCE) were performed to evaluate understanding, knowledge retention, and counseling skills. A linear mixed effect model with a random intercept analysis for pre-test, post-test, and retention test scores showed significant higher result for intervention group compared to control group (p < 0.001). Comprehensive knowledge and counselling skills were better in the intervention group than in the control group as shown by the OSCE score (68.6 vs 59.3, p < 0.001). Our comprehensive integrated infant feeding practice module, which incorporates multidisciplinary learning processes and an interactive hands-on workshop with a role-play session yields better knowledge understanding and counseling skills compared with the existing module. Comprehensive knowledge and good counseling skills of medical students as future doctors are a pre-requisite to provide effective education to parents to support successful infant feeding practices.

All-optical liquid crystal spatial light modulators

NASA Astrophysics Data System (ADS)

Tabiryan, Nelson; Grozhik, Vladimir; Khoo, Iam Choon; Nersisyan, Sarik R.; Serak, Svetlana

2003-12-01

Nonlinear optical processes in liquid crystals (LC) can be used for construction of all-optical spatial light modulators (SLM) where the photosensitivity and phase modulating functions are integrated into a single layer of an LC-material. Such spatial light integrated modulators (SLIMs) cost only a fraction of the conventional LC-SLM and can be used with high power laser radiation due to high transparency of LC materials and absence of light absorbing electrodes on the substrates of the LC-cell constituting the SLIM. Recent development of LC materials the photosensitivity of which is comparable to that of semiconductors has led to using SLIM in schemes of optical anti-jamming, sensor protection, and image processing. All-optical processes add remarkable versatility to the operation of SLIM harnessing the wealth inherent to light-matter interaction phenomena.

Very-low-power and footprint integrated photonic modulators and switches for ICT

NASA Astrophysics Data System (ADS)

Thylén, Lars; Holmström, Petter; Wosinski, Lech

2013-03-01

The current development in photonics for communications and interconnects pose increasing requirements on reduction of footprint, power dissipation and cost, as well as increased bandwidth. Integrated nanophotonics has been viewed as one solution to this, capitalizing on development in nanotechnology as such as well as on increased insights into light matter interaction on the nanoscale. The latter can be exemplified by plasmonics and low-dimensional semiconductors such as quantum dots (QDs). In this scenario the development of better electrooptic materials is also of great importance, the electrooptic polymers being an example, since they potentially offer improved properties for optical phase modulators in terms of power and probably cost and general flexibility. Phase modulators are essential for e.g. the rapidly developing advanced modulation formats for telecom, since phase modulation basically can generate any type of modulation. The electrooptic polymers, e.g. in combination with plasmonics nanoparticle array waveguides or nanostructured hybrid plasmonic media can theoretically give extremely compact and low power dissipation modulators, still to be demonstrated. The low-dimensional semiconductors, e.g. in the shape of QDs, can be employed for modulation or switching functions, offering possibilities in the future for scaling to 2 or 3 dimensions for advanced switching functions. In both the plasmonics and QD cases, nanosizing and low power dissipation are generally due to near-field interactions, albeit being of different physical origin in the two cases. A comparison of all-optical and electronically controlled switching is given.

Refraction of dispersive shock waves

NASA Astrophysics Data System (ADS)

El, G. A.; Khodorovskii, V. V.; Leszczyszyn, A. M.

2012-09-01

We study a dispersive counterpart of the classical gas dynamics problem of the interaction of a shock wave with a counter-propagating simple rarefaction wave, often referred to as the shock wave refraction. The refraction of a one-dimensional dispersive shock wave (DSW) due to its head-on collision with the centred rarefaction wave (RW) is considered in the framework of the defocusing nonlinear Schrödinger (NLS) equation. For the integrable cubic nonlinearity case we present a full asymptotic description of the DSW refraction by constructing appropriate exact solutions of the Whitham modulation equations in Riemann invariants. For the NLS equation with saturable nonlinearity, whose modulation system does not possess Riemann invariants, we take advantage of the recently developed method for the DSW description in non-integrable dispersive systems to obtain main physical parameters of the DSW refraction. The key features of the DSW-RW interaction predicted by our modulation theory analysis are confirmed by direct numerical solutions of the full dispersive problem.

Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

PubMed

Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

2017-10-01

The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

Metastability and Inter-Band Frequency Modulation in Networks of Oscillating Spiking Neuron Populations

PubMed Central

Bhowmik, David; Shanahan, Murray

2013-01-01

Groups of neurons firing synchronously are hypothesized to underlie many cognitive functions such as attention, associative learning, memory, and sensory selection. Recent theories suggest that transient periods of synchronization and desynchronization provide a mechanism for dynamically integrating and forming coalitions of functionally related neural areas, and that at these times conditions are optimal for information transfer. Oscillating neural populations display a great amount of spectral complexity, with several rhythms temporally coexisting in different structures and interacting with each other. This paper explores inter-band frequency modulation between neural oscillators using models of quadratic integrate-and-fire neurons and Hodgkin-Huxley neurons. We vary the structural connectivity in a network of neural oscillators, assess the spectral complexity, and correlate the inter-band frequency modulation. We contrast this correlation against measures of metastable coalition entropy and synchrony. Our results show that oscillations in different neural populations modulate each other so as to change frequency, and that the interaction of these fluctuating frequencies in the network as a whole is able to drive different neural populations towards episodes of synchrony. Further to this, we locate an area in the connectivity space in which the system directs itself in this way so as to explore a large repertoire of synchronous coalitions. We suggest that such dynamics facilitate versatile exploration, integration, and communication between functionally related neural areas, and thereby supports sophisticated cognitive processing in the brain. PMID:23614040

Meteorological Instrumentation and Measurements Open Resource Training Modules for Undergraduate and Graduate Education

NASA Astrophysics Data System (ADS)

Rockwell, A.; Clark, R. D.; Stevermer, A.

2017-12-01

The National Center for Atmospheric Research Earth Observing Laboratory, Millersville University and The COMET Program are collaborating to produce a series of nine online modules on the the topic of meteorological instrumentation and measurements. These interactive, multimedia educational modules can be integrated into undergraduate and graduate meteorology courses on instrumentation, measurement science, and observing systems to supplement traditional pedagogies and enhance blended instruction. These freely available and open-source training tools are designed to supplement traditional pedagogies and enhance blended instruction. Three of the modules are now available and address the theory and application of Instrument Performance Characteristics, Meteorological Temperature Instrumentation and Measurements, and Meteorological Pressure Instrumentation and Measurements. The content of these modules is of the highest caliber as it has been developed by scientists and engineers who are at the forefront of the field of observational science. Communicating the availability of these unique and influential educational resources with the community is of high priority. These modules will have a profound effect on the atmospheric observational sciences community by fulfilling a need for contemporary, interactive, multimedia guided education and training modules integrating the latest instructional design and assessment tools in observational science. Thousands of undergraduate and graduate students will benefit, while course instructors will value a set of high quality modules to use as supplements to their courses. The modules can serve as an alternative to observational research training and fill the void between field projects or assist those schools that lack the resources to stage a field- or laboratory-based instrumentation experience.

Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails.

PubMed

Benleulmi, Mohamed S; Matysiak, Julien; Robert, Xavier; Miskey, Csaba; Mauro, Eric; Lapaillerie, Delphine; Lesbats, Paul; Chaignepain, Stéphane; Henriquez, Daniel R; Calmels, Christina; Oladosu, Oyindamola; Thierry, Eloïse; Leon, Oscar; Lavigne, Marc; Andreola, Marie-Line; Delelis, Olivier; Ivics, Zoltán; Ruff, Marc; Gouet, Patrice; Parissi, Vincent

2017-11-28

Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method.

PubMed

Jiang, T; Jiang, C-Y; Shu, J-H; Xu, Y-J

2017-07-10

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Functional modules by relating protein interaction networks and gene expression.

PubMed

Tornow, Sabine; Mewes, H W

2003-11-01

Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships.

Functional modules by relating protein interaction networks and gene expression

PubMed Central

Tornow, Sabine; Mewes, H. W.

2003-01-01

Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships. PMID:14576317

PIPE: a protein–protein interaction passage extraction module for BioCreative challenge

PubMed Central

Chu, Chun-Han; Su, Yu-Chen; Chen, Chien Chin; Hsu, Wen-Lian

2016-01-01

Identifying the interactions between proteins mentioned in biomedical literatures is one of the frequently discussed topics of text mining in the life science field. In this article, we propose PIPE, an interaction pattern generation module used in the Collaborative Biocurator Assistant Task at BioCreative V (http://www.biocreative.org/) to capture frequent protein-protein interaction (PPI) patterns within text. We also present an interaction pattern tree (IPT) kernel method that integrates the PPI patterns with convolution tree kernel (CTK) to extract PPIs. Methods were evaluated on LLL, IEPA, HPRD50, AIMed and BioInfer corpora using cross-validation, cross-learning and cross-corpus evaluation. Empirical evaluations demonstrate that our method is effective and outperforms several well-known PPI extraction methods. Database URL: PMID:27524807

Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

PubMed

Hage, Steffen R; Nieder, Andreas

2015-05-06

Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

Integration and Evaluation of Substance Abuse Research Education Training (SARET) into a Master of Social Work program.

PubMed

Tuchman, Ellen; Hanley, Kathleen; Naegle, Madeline; More, Frederick; Bereket, Sewit; Gourevitch, Marc N

2017-01-01

The Substance Abuse Research and Education Training (SARET) program is funded by the National Institutes of Drug Abuse in 2006 as a novel approach to spark interest in substance abuse research among medical, dental, nursing, and social work graduate students through a Web-based curriculum and research mentorships. This report presents the initial integration of the intervention in a Master of Social Work (MSW) program, the components of the program, and the mixed-methods evaluation of its effect on students' attitudes towards substance abuse research and treatment. SARET comprises 2 main components: stipend-supported research mentorships and a Web-based module series, consisting of 6 interactive, multimedia modules addressing core SA research topics, delivered via course curricula and in the research mentorships. An initial evaluation was designed to assess SARET's acceptability and short-term impact on participants' interest in SA research. The components of this Web-based curriculum evaluation include focus group feedback on the relevance of the modules to SW students, number of courses into which the modules were integrated with number of module completions, changes in interest in SA research associated with module completion. The full series of Web-based modules has been integrated across several courses in the social work curriculum, and social work students have become integral participants in the summer mentored research experience. One hundred eighteen students completed at least 1 module and 42 students completed all 6 modules. Neurobiology, Screening, and Epidemiology were the most widely viewed modules. Students reported positive impact on their vision of SA-related clinical care, more positive attitudes about conducting research, and in some cases, change in career. The SARET program's modules and summer mentored research increased clinical and research interest related to SUDs, as well as interprofessional attitudes among social work students. Participants have shown some early research success. Longer-term follow-up will enable us to continue to assess the effectiveness of the program.

Protein-protein interaction networks: unraveling the wiring of molecular machines within the cell.

PubMed

De Las Rivas, Javier; Fontanillo, Celia

2012-11-01

Mapping and understanding of the protein interaction networks with their key modules and hubs can provide deeper insights into the molecular machinery underlying complex phenotypes. In this article, we present the basic characteristics and definitions of protein networks, starting with a distinction of the different types of associations between proteins. We focus the review on protein-protein interactions (PPIs), a subset of associations defined as physical contacts between proteins that occur by selective molecular docking in a particular biological context. We present such definition as opposed to other types of protein associations derived from regulatory, genetic, structural or functional relations. To determine PPIs, a variety of binary and co-complex methods exist; however, not all the technologies provide the same information and data quality. A way of increasing confidence in a given protein interaction is to integrate orthogonal experimental evidences. The use of several complementary methods testing each single interaction assesses the accuracy of PPI data and tries to minimize the occurrence of false interactions. Following this approach there have been important efforts to unify primary databases of experimentally proven PPIs into integrated databases. These meta-databases provide a measure of the confidence of interactions based on the number of experimental proofs that report them. As a conclusion, we can state that integrated information allows the building of more reliable interaction networks. Identification of communities, cliques, modules and hubs by analysing the topological parameters and graph properties of the protein networks allows the discovery of central/critical nodes, which are candidates to regulate cellular flux and dynamics.

A web server for analysis, comparison and prediction of protein ligand binding sites.

PubMed

Singh, Harinder; Srivastava, Hemant Kumar; Raghava, Gajendra P S

2016-03-25

One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom .

Posttranslational Modifications and Plant-Environment Interaction.

PubMed

Hashiguchi, A; Komatsu, S

2017-01-01

Posttranslational modifications (PTMs) of proteins such as phosphorylation and ubiquitination are crucial for controlling protein stability, localization, and conformation. Genetic information encoded in DNA is transcribed, translated, and increases its complexity by multiple PTMs. Conformational change introduced by PTMs affects interacting partners of each proteins and their downstream signaling; therefore, PTMs are the major level of modulations of total outcome of living cells. Plants are living in harsh environment that requires unremitting physiological modulation to survive, and the plant response to various environment stresses is regulated by PTMs of proteins. This review deals with the novel knowledge of PTM-focused proteomic studies on various life conditions. PTMs are focused that mediate plant-environment interaction such as stress perception, protein homeostasis, control of energy shift, and defense by immune system. Integration of diverse signals on a protein via multiple PTMs is discussed as well, considering current situation where signal integration became an emerging area approached by systems biology into account. © 2017 Elsevier Inc. All rights reserved.

Social dominance modulates eavesdropping in zebrafish

PubMed Central

Abril-de-Abreu, Rodrigo; Cruz, Ana S.; Oliveira, Rui F.

2015-01-01

Group living animals may eavesdrop on signalling interactions between conspecifics and integrate it with their own past social experience in order to optimize the use of relevant information from others. However, little is known about this interplay between public (eavesdropped) and private social information. To investigate it, we first manipulated the dominance status of bystander zebrafish. Next, we either allowed or prevented bystanders from observing a fight. Finally, we assessed their behaviour towards the winners and losers of the interaction, using a custom-made video-tracking system and directional analysis. We found that only dominant bystanders who had seen the fight revealed a significant increase in directional focus (a measure of attention) towards the losers of the fights. Furthermore, our results indicate that information about the fighters' acquired status was collected from the signalling interaction itself and not from post-interaction status cues, which implies the existence of individual recognition in zebrafish. Thus, we show for the first time that zebrafish, a highly social model organism, eavesdrop on conspecific agonistic interactions and that this process is modulated by the eavesdroppers' dominance status. We suggest that this type of integration of public and private information may be ubiquitous in social learning processes. PMID:26361550

NCC: A Multidisciplinary Design/Analysis Tool for Combustion Systems

NASA Technical Reports Server (NTRS)

Liu, Nan-Suey; Quealy, Angela

1999-01-01

A multi-disciplinary design/analysis tool for combustion systems is critical for optimizing the low-emission, high-performance combustor design process. Based on discussions between NASA Lewis Research Center and the jet engine companies, an industry-government team was formed in early 1995 to develop the National Combustion Code (NCC), which is an integrated system of computer codes for the design and analysis of combustion systems. NCC has advanced features that address the need to meet designer's requirements such as "assured accuracy", "fast turnaround", and "acceptable cost". The NCC development team is comprised of Allison Engine Company (Allison), CFD Research Corporation (CFDRC), GE Aircraft Engines (GEAE), NASA Lewis Research Center (LeRC), and Pratt & Whitney (P&W). This development team operates under the guidance of the NCC steering committee. The "unstructured mesh" capability and "parallel computing" are fundamental features of NCC from its inception. The NCC system is composed of a set of "elements" which includes grid generator, main flow solver, turbulence module, turbulence and chemistry interaction module, chemistry module, spray module, radiation heat transfer module, data visualization module, and a post-processor for evaluating engine performance parameters. Each element may have contributions from several team members. Such a multi-source multi-element system needs to be integrated in a way that facilitates inter-module data communication, flexibility in module selection, and ease of integration.

The Fluids Integrated Rack and Light Microscopy Module Integrated Capabilities

NASA Technical Reports Server (NTRS)

Motil, Susan M.; Gati, Frank; Snead, John H.; Hill, Myron E.; Griffin, DeVon W.

2003-01-01

The Fluids Integrated Rack (FIR), a facility class payload, and the Light Microscopy Module (LMM), a subrack payload, are scheduled to be launched in 2005. The LMM integrated into the FIR will provide a unique platform for conducting fluids and biological experiments on ISS. The FIR is a modular, multi-user scientific research facility that will fly in the U.S. laboratory module, Destiny, of the International Space Station (ISS). The first payload in the FIR will be the Light Microscopy Module (LMM). The LMM is planned as a remotely controllable, automated, on-orbit microscope subrack facility, allowing flexible scheduling and control of fluids and biology experiments within the FIR. Key diagnostic capabilities for meeting science requirements include video microscopy to observe microscopic phenomena and dynamic interactions, interferometry to make thin film measurements with nanometer resolution, laser tweezers for particle manipulation, confocal microscopy to provide enhanced three-dimensional visualization of structures, and spectrophotometry to measure photonic properties of materials. The LMM also provides experiment sample containment for frangibles and fluids. This paper will provide a description of the current FIR and LMM designs, planned capabilities and key features. In addition a brief description of the initial five experiments planned for LMM/FIR will be provided.

An Integrated Simulation Module for Cyber-Physical Automation Systems †

PubMed Central

Ferracuti, Francesco; Freddi, Alessandro; Monteriù, Andrea; Prist, Mariorosario

2016-01-01

The integration of Wireless Sensors Networks (WSNs) into Cyber Physical Systems (CPSs) is an important research problem to solve in order to increase the performances, safety, reliability and usability of wireless automation systems. Due to the complexity of real CPSs, emulators and simulators are often used to replace the real control devices and physical connections during the development stage. The most widespread simulators are free, open source, expandable, flexible and fully integrated into mathematical modeling tools; however, the connection at a physical level and the direct interaction with the real process via the WSN are only marginally tackled; moreover, the simulated wireless sensor motes are not able to generate the analogue output typically required for control purposes. A new simulation module for the control of a wireless cyber-physical system is proposed in this paper. The module integrates the COntiki OS JAva Simulator (COOJA), a cross-level wireless sensor network simulator, and the LabVIEW system design software from National Instruments. The proposed software module has been called “GILOO” (Graphical Integration of Labview and cOOja). It allows one to develop and to debug control strategies over the WSN both using virtual or real hardware modules, such as the National Instruments Real-Time Module platform, the CompactRio, the Supervisory Control And Data Acquisition (SCADA), etc. To test the proposed solution, we decided to integrate it with one of the most popular simulators, i.e., the Contiki OS, and wireless motes, i.e., the Sky mote. As a further contribution, the Contiki Sky DAC driver and a new “Advanced Sky GUI” have been proposed and tested in the COOJA Simulator in order to provide the possibility to develop control over the WSN. To test the performances of the proposed GILOO software module, several experimental tests have been made, and interesting preliminary results are reported. The GILOO module has been applied to a smart home mock-up where a networked control has been developed for the LED lighting system. PMID:27164109

An Integrated Simulation Module for Cyber-Physical Automation Systems.

PubMed

Ferracuti, Francesco; Freddi, Alessandro; Monteriù, Andrea; Prist, Mariorosario

2016-05-05

The integration of Wireless Sensors Networks (WSNs) into Cyber Physical Systems (CPSs) is an important research problem to solve in order to increase the performances, safety, reliability and usability of wireless automation systems. Due to the complexity of real CPSs, emulators and simulators are often used to replace the real control devices and physical connections during the development stage. The most widespread simulators are free, open source, expandable, flexible and fully integrated into mathematical modeling tools; however, the connection at a physical level and the direct interaction with the real process via the WSN are only marginally tackled; moreover, the simulated wireless sensor motes are not able to generate the analogue output typically required for control purposes. A new simulation module for the control of a wireless cyber-physical system is proposed in this paper. The module integrates the COntiki OS JAva Simulator (COOJA), a cross-level wireless sensor network simulator, and the LabVIEW system design software from National Instruments. The proposed software module has been called "GILOO" (Graphical Integration of Labview and cOOja). It allows one to develop and to debug control strategies over the WSN both using virtual or real hardware modules, such as the National Instruments Real-Time Module platform, the CompactRio, the Supervisory Control And Data Acquisition (SCADA), etc. To test the proposed solution, we decided to integrate it with one of the most popular simulators, i.e., the Contiki OS, and wireless motes, i.e., the Sky mote. As a further contribution, the Contiki Sky DAC driver and a new "Advanced Sky GUI" have been proposed and tested in the COOJA Simulator in order to provide the possibility to develop control over the WSN. To test the performances of the proposed GILOO software module, several experimental tests have been made, and interesting preliminary results are reported. The GILOO module has been applied to a smart home mock-up where a networked control has been developed for the LED lighting system.

Dense module enumeration in biological networks

NASA Astrophysics Data System (ADS)

Tsuda, Koji; Georgii, Elisabeth

2009-12-01

Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

Functional Module Analysis for Gene Coexpression Networks with Network Integration.

PubMed

Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

2015-01-01

Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

Building blocks of a fish head: Developmental and variational modularity in a complex system.

PubMed

Lehoux, Caroline; Cloutier, Richard

2015-11-01

Evolution of the vertebrate skull is developmentally constrained by the interactions among its anatomical systems, such as the dermatocranium and the sensory system. The interaction between the dermal bones and lateral line canals has been debated for decades but their morphological integration has never been tested. An ontogenetic series of 97 juvenile and adult Amia calva (Actinopterygii) was used to describe the patterning and modularity of sensory lateral line canals and their integration with supporting cranial bones. Developmental modules were tested for the otic canal and supratemporal commissure by computing correlations in the branching sequence of groups of pores. Landmarks were digitized on 25 specimens to test a priori hypotheses of variational and developmental modularity at the level of canals and dermal bones. Branching sequence suggests a specific patterning supported by significant positive correlations in the sequence of appearance of branches between bilateral sides. Differences in patterning between the otic canal and the supratemporal commissure and tests of modularity with geometric morphometrics suggest that both canals form distinct modules. The integration between bones and canals was insufficient to detect a module. However, both components were not independent. Groups of pores tended to disappear without affecting other groups of pores suggesting that they are quasi-independent units acting as modules. This study provides evidence of a hierarchical organization for the modular sensory system that could explain variation of pattern of canals among species and their association with dermal bones. © 2015 Wiley Periodicals, Inc.

Towards a Comprehensive Computational Simulation System for Turbomachinery

NASA Technical Reports Server (NTRS)

Shih, Ming-Hsin

1994-01-01

The objective of this work is to develop algorithms associated with a comprehensive computational simulation system for turbomachinery flow fields. This development is accomplished in a modular fashion. These modules includes grid generation, visualization, network, simulation, toolbox, and flow modules. An interactive grid generation module is customized to facilitate the grid generation process associated with complicated turbomachinery configurations. With its user-friendly graphical user interface, the user may interactively manipulate the default settings to obtain a quality grid within a fraction of time that is usually required for building a grid about the same geometry with a general-purpose grid generation code. Non-Uniform Rational B-Spline formulations are utilized in the algorithm to maintain geometry fidelity while redistributing grid points on the solid surfaces. Bezier curve formulation is used to allow interactive construction of inner boundaries. It is also utilized to allow interactive point distribution. Cascade surfaces are transformed from three-dimensional surfaces of revolution into two-dimensional parametric planes for easy manipulation. Such a transformation allows these manipulated plane grids to be mapped to surfaces of revolution by any generatrix definition. A sophisticated visualization module is developed to al-low visualization for both grid and flow solution, steady or unsteady. A network module is built to allow data transferring in the heterogeneous environment. A flow module is integrated into this system, using an existing turbomachinery flow code. A simulation module is developed to combine the network, flow, and visualization module to achieve near real-time flow simulation about turbomachinery geometries. A toolbox module is developed to support the overall task. A batch version of the grid generation module is developed to allow portability and has been extended to allow dynamic grid generation for pitch changing turbomachinery configurations. Various applications with different characteristics are presented to demonstrate the success of this system.

Differential Modulation of Functional Dynamics and Allosteric Interactions in the Hsp90-Cochaperone Complexes with p23 and Aha1: A Computational Study

PubMed Central

Blacklock, Kristin; Verkhivker, Gennady M.

2013-01-01

Allosteric interactions of the molecular chaperone Hsp90 with a large cohort of cochaperones and client proteins allow for molecular communication and event coupling in signal transduction networks. The integration of cochaperones into the Hsp90 system is driven by the regulatory mechanisms that modulate the progression of the ATPase cycle and control the recruitment of the Hsp90 clientele. In this work, we report the results of computational modeling of allosteric regulation in the Hsp90 complexes with the cochaperones p23 and Aha1. By integrating protein docking, biophysical simulations, modeling of allosteric communications, protein structure network analysis and the energy landscape theory we have investigated dynamics and stability of the Hsp90-p23 and Hsp90-Aha1 interactions in direct comparison with the extensive body of structural and functional experiments. The results have revealed that functional dynamics and allosteric interactions of Hsp90 can be selectively modulated by these cochaperones via specific targeting of the regulatory hinge regions that could restrict collective motions and stabilize specific chaperone conformations. The protein structure network parameters have quantified the effects of cochaperones on conformational stability of the Hsp90 complexes and identified dynamically stable communities of residues that can contribute to the strengthening of allosteric interactions. According to our results, p23-mediated changes in the Hsp90 interactions may provide “molecular brakes” that could slow down an efficient transmission of the inter-domain allosteric signals, consistent with the functional role of p23 in partially inhibiting the ATPase cycle. Unlike p23, Aha1-mediated acceleration of the Hsp90-ATPase cycle may be achieved via modulation of the equilibrium motions that facilitate allosteric changes favoring a closed dimerized form of Hsp90. The results of our study have shown that Aha1 and p23 can modulate the Hsp90-ATPase activity and direct the chaperone cycle by exerting the precise control over structural stability, global movements and allosteric communications in Hsp90. PMID:23977182

Virtual- and real-world operation of mobile robotic manipulators: integrated simulation, visualization, and control environment

NASA Astrophysics Data System (ADS)

Chen, ChuXin; Trivedi, Mohan M.

1992-03-01

This research is focused on enhancing the overall productivity of an integrated human-robot system. A simulation, animation, visualization, and interactive control (SAVIC) environment has been developed for the design and operation of an integrated robotic manipulator system. This unique system possesses the abilities for multisensor simulation, kinematics and locomotion animation, dynamic motion and manipulation animation, transformation between real and virtual modes within the same graphics system, ease in exchanging software modules and hardware devices between real and virtual world operations, and interfacing with a real robotic system. This paper describes a working system and illustrates the concepts by presenting the simulation, animation, and control methodologies for a unique mobile robot with articulated tracks, a manipulator, and sensory modules.

Multilayered metal-insulator nanocavities: toward tunable multi-resonance nano-devices for integrated optics

NASA Astrophysics Data System (ADS)

Song, Junyeob; Zhou, Wei

2017-02-01

Plasmonic nanocavities can control light flows and enhance light-mater interactions at subwavelength scale, and thus can potentially be used as nanoscale components in integrated optics systems either for passive optical coupling, or for active optical modulation and emission. In this work, we investigated a new type of multilayered metal-insulator optical nanocavities that can support multiple localized plasmon resonances with ultra-small mode volumes. The total number of resonance peaks and their resonance wavelengths can be freely and accurately controlled by simple geometric design rules. Multi-resonance plasmonic nanocavities can serve as a nanoscale wavelength-multiplexed optical components in integrated optics systems, such as optical couplers, light emitters, nanolasers, optical sensors, and optical modulators.

Overview of the NCC

NASA Technical Reports Server (NTRS)

Liu, Nan-Suey

2001-01-01

A multi-disciplinary design/analysis tool for combustion systems is critical for optimizing the low-emission, high-performance combustor design process. Based on discussions between then NASA Lewis Research Center and the jet engine companies, an industry-government team was formed in early 1995 to develop the National Combustion Code (NCC), which is an integrated system of computer codes for the design and analysis of combustion systems. NCC has advanced features that address the need to meet designer's requirements such as "assured accuracy", "fast turnaround", and "acceptable cost". The NCC development team is comprised of Allison Engine Company (Allison), CFD Research Corporation (CFDRC), GE Aircraft Engines (GEAE), NASA Glenn Research Center (LeRC), and Pratt & Whitney (P&W). The "unstructured mesh" capability and "parallel computing" are fundamental features of NCC from its inception. The NCC system is composed of a set of "elements" which includes grid generator, main flow solver, turbulence module, turbulence and chemistry interaction module, chemistry module, spray module, radiation heat transfer module, data visualization module, and a post-processor for evaluating engine performance parameters. Each element may have contributions from several team members. Such a multi-source multi-element system needs to be integrated in a way that facilitates inter-module data communication, flexibility in module selection, and ease of integration. The development of the NCC beta version was essentially completed in June 1998. Technical details of the NCC elements are given in the Reference List. Elements such as the baseline flow solver, turbulence module, and the chemistry module, have been extensively validated; and their parallel performance on large-scale parallel systems has been evaluated and optimized. However the scalar PDF module and the Spray module, as well as their coupling with the baseline flow solver, were developed in a small-scale distributed computing environment. As a result, the validation of the NCC beta version as a whole was quite limited. Current effort has been focused on the validation of the integrated code and the evaluation/optimization of its overall performance on large-scale parallel systems.

NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise

PubMed Central

Wong, Victor C.; Bass, Victor L.; Bullock, M. Elise; Chavali, Arvind K.; Lee, Robin E.C.; Mothes, Walther; Gaudet, Suzanne; Miller-Jensen, Kathryn

2018-01-01

SUMMARY Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation. For a given integration site, live-cell imaging shows that NF-κB activation correlates with viral activation, but across integration sites, NF-κB activation cannot account for differences in transcriptional noise and phenotypes. Instead, differences in transcriptional noise are associated with differences in chromatin state and RNA polymerase II regulation. We conclude that, whereas NF-κB regulates transcript abundance in each cell, the chromatin environment modulates noise in the population to support diverse HIV activation in response to TNF. PMID:29346759

Development of the engineering design integration (EDIN) system: A computer aided design development

NASA Technical Reports Server (NTRS)

Glatt, C. R.; Hirsch, G. N.

1977-01-01

The EDIN (Engineering Design Integration) System which provides a collection of hardware and software, enabling the engineer to perform man-in-the-loop interactive evaluation of aerospace vehicle concepts, was considered. Study efforts were concentrated in the following areas: (1) integration of hardware with the Univac Exec 8 System; (2) development of interactive software for the EDIN System; (3) upgrading of the EDIN technology module library to an interactive status; (4) verification of the soundness of the developing EDIN System; (5) support of NASA in design analysis studies using the EDIN System; (6) provide training and documentation in the use of the EDIN System; and (7) provide an implementation plan for the next phase of development and recommendations for meeting long range objectives.

Meteorological Instrumentation and Measurements Open Resource Training Modules for Undergraduate and Graduate Education

NASA Astrophysics Data System (ADS)

Rockwell, A.; Clark, R. D.; Stevermer, A.

2016-12-01

The study of observational science crosses all other subject areas and requires a new innovative paradigm: a collaboration of experts to create high quality, content-rich learning modules that will elevate the scientific literacy and technical competency of undergraduate and graduate students. This collaborative project will design, develop, and openly distribute a series of interactive, multimedia, online modules that can be effectively integrated into meteorology courses on instrumentation, measurement science, and observing systems to supplement traditional pedagogies and enhance blended instruction. The modules will address topics such as principles of instrumentation and measurement to the theory and practice of measuring a host of meteorological variables. The impact will have a profound effect on the atmospheric observational sciences community by fulfilling a need for contemporary, interactive, multimedia guided education and training modules integrating the latest instructional design and assessment tools in observational science. Thousands of undergraduate and graduate students will benefit, while course instructors will value a set of high quality modules to use as supplements to their courses. The modules can serve as an alternative to observational research training and fill the void between field projects or assist those schools that lack the resources to stage a field- or laboratory-based instrumentation experience. This project brings together the intellectual capital of the scientists and engineers of National Center for Atmospheric Research Earth Observing Laboratory as subject matter experts, the artistic talents and instructional design acumen of the COMET program, and the project leadership, vision, teaching expertise in instruments and observational science at Millersville University.

Plant hormone signaling lightens up: integrators of light and hormones.

PubMed

Lau, On Sun; Deng, Xing Wang

2010-10-01

Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3-LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact. Copyright © 2010 Elsevier Ltd. All rights reserved.

NREL/industry interaction: Amorphous silicon alloy research team formation

NASA Astrophysics Data System (ADS)

Luft, Werner

1994-06-01

The low material cost and proven manufacturability of amorphous silicon (a-Si) alloy photovoltaic technology make it ideally suited for large-scale terrestrial applications. The present efficiency of a-Si alloy modules is, however, much lower than the 15% stable efficiency that would lead to significant penetration of the electric utility bulk-power market. The slow progress in achieving high stabilized a-Si alloy module efficiencies may in part be attributed to the fact that only in the last few years did we emphasize stable efficiencies. A mission-focused integrated effort among the a-Si PV industry, universities, and the National Renewable Energy Laboratory (NREL) would help. To foster research integration, NREL has established four research teams with significant industry participation. In the 11 months since the research team formation, a close interaction among the a-Si PV industry, universities, and NREL has been achieved and has resulted in mission-directed research.

NREL/industry interaction: Amorphous silicon alloy research team formation

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

Luft, W.

1994-06-30

The low material cost and proven manufacturability of amorphous silicon (a-Si) alloy photovoltaic technology make it ideally suited for large-scale terrestrial applications. The present efficiency of a-Si alloy modules is, however, much lower than the 15% stable efficiency that would lead to [ital significant] penetration of the electric utility bulk-power market. The slow progress in achieving high stabilized a-Si alloy module efficiencies may in part be attributed to the fact that only in the last few years did we emphasize stable efficiencies. A mission-focused integrated effort among the a-Si PV industry, universities, and the National Renewable Energy Laboratory (NREL) wouldmore » help. To foster research integration, NREL has established four research teams with significant industry participation. In the 11 months since the research team formation, a close interaction among the a-Si PV industry, universities, and NREL has been achieved and has resulted in mission-directed research.« less

A SPECT system simulator built on the SolidWorks TM 3D-Design package.

PubMed

Li, Xin; Furenlid, Lars R

2014-08-17

We have developed a GPU-accelerated SPECT system simulator that integrates into instrument-design workflow [1]. This simulator includes a gamma-ray tracing module that can rapidly propagate gamma-ray photons through arbitrary apertures modeled by SolidWorks TM -created stereolithography (.STL) representations with a full complement of physics cross sections [2, 3]. This software also contains a scintillation detector simulation module that can model a scintillation detector with arbitrary scintillation crystal shape and light-sensor arrangement. The gamma-ray tracing module enables us to efficiently model aperture and detector crystals in SolidWorks TM and save them as STL file format, then load the STL-format model into this module to generate list-mode results of interacted gamma-ray photon information (interaction positions and energies) inside the detector crystals. The Monte-Carlo scintillation detector simulation module enables us to simulate how scintillation photons get reflected, refracted and absorbed inside a scintillation detector, which contributes to more accurate simulation of a SPECT system.

A SPECT system simulator built on the SolidWorksTM 3D design package

NASA Astrophysics Data System (ADS)

Li, Xin; Furenlid, Lars R.

2014-09-01

We have developed a GPU-accelerated SPECT system simulator that integrates into instrument-design work flow [1]. This simulator includes a gamma-ray tracing module that can rapidly propagate gamma-ray photons through arbitrary apertures modeled by SolidWorksTM-created stereolithography (.STL) representations with a full com- plement of physics cross sections [2, 3]. This software also contains a scintillation detector simulation module that can model a scintillation detector with arbitrary scintillation crystal shape and light-sensor arrangement. The gamma-ray tracing module enables us to efficiently model aperture and detector crystals in SolidWorksTM and save them as STL file format, then load the STL-format model into this module to generate list-mode results of interacted gamma-ray photon information (interaction positions and energies) inside the detector crystals. The Monte-Carlo scintillation detector simulation module enables us to simulate how scintillation photons get reflected, refracted and absorbed inside a scintillation detector, which contributes to more accurate simulation of a SPECT system.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high-speed network capabilities. The BioSIGHT project at is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches toward the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross-disciplinary in nature and requires expertise from many areas including Biology, Computer Science Electrical Engineering, Education, and the Cognitive Sciences. The BioSIGHT team includes a scientific illustrator, educational software designer, computer programmers as well as IMSC graduate and undergraduate students.

A deterministic guide for material and mode dependence of on-chip electro-optic modulator performance

NASA Astrophysics Data System (ADS)

Amin, Rubab; Suer, Can; Ma, Zhizhen; Sarpkaya, Ibrahim; Khurgin, Jacob B.; Agarwal, Ritesh; Sorger, Volker J.

2017-10-01

Electro-optic modulation is a key function in optical data communication and possible future optical computing engines. The performance of modulators intricately depends on the interaction between the actively modulated material and the propagating waveguide mode. While high-performing modulators were demonstrated before, the approaches were taken as ad-hoc. Here we show the first systematic investigation to incorporate a holistic analysis for high-performance and ultra-compact electro-optic modulators on-chip. We show that intricate interplay between active modulation material and optical mode plays a key role in the device operation. Based on physical tradeoffs such as index modulation, loss, optical confinement factors and slow-light effects, we find that bias-material-mode regions exist where high phase modulation and high loss (absorption) modulation is found. This work paves the way for a holistic design rule of electro-optic modulators for on-chip integration.

Support systems of the orbiting quarantine facility

NASA Technical Reports Server (NTRS)

1981-01-01

The physical support systems, the personnel management structure, and the contingency systems necessary to permit the Orbiting Quarantine Facility (OQF) to function as an integrated system are described. The interactions between the subsystems within the preassembled modules are illustrated. The Power Module generates and distributes electrical power throughout each of the four modules, stabilizes the OQF's attitude, and dissipates heat generated throughout the system. The Habitation Module is a multifunctional structure designed to monitor and control all aspects of the system's activities. The Logistics Module stores the supplies needed for 30 days of operation and provides storage for waste materials generated during the mission. The Laboratory Module contains the equipment necessary for executing the protocol, as well as an independent life support system.

Investigation of candidate genes for osteoarthritis based on gene expression profiles.

PubMed

Dong, Shuanghai; Xia, Tian; Wang, Lei; Zhao, Qinghua; Tian, Jiwei

2016-12-01

To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules. In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs were involved in inflammatory response, while down-regulated DEGs were involved in cell cycle. PPI network with 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle. The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for gene therapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle and cytokine-cytokine receptor interaction pathway. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

CFD application to supersonic/hypersonic inlet airframe integration. [computational fluid dynamics (CFD)

NASA Technical Reports Server (NTRS)

Benson, Thomas J.

1988-01-01

Supersonic external compression inlets are introduced, and the computational fluid dynamics (CFD) codes and tests needed to study flow associated with these inlets are outlined. Normal shock wave turbulent boundary layer interaction is discussed. Boundary layer control is considered. Glancing sidewall shock interaction is treated. The CFD validation of hypersonic inlet configurations is explained. Scramjet inlet modules are shown.

Developing and Implementing an Interactive End-of-Life Education Module Using Raptivity and iSpring: Lessons Learned

ERIC Educational Resources Information Center

Lewis-Pierre, LaToya; Aziza, Khitam

2017-01-01

The 21st century nurse is a forward-thinking individual who is expected to deliver holistic nursing care. Multigenerational learners are seeking degrees and the new Net generation learner will reflect the majority of the workforce. Thus, the integration of a multilevel interactive classroom is instrumental in facilitating the student's knowledge…

GLADIATOR: a global approach for elucidating disease modules.

PubMed

Silberberg, Yael; Kupiec, Martin; Sharan, Roded

2017-05-26

Understanding the genetic basis of disease is an important challenge in biology and medicine. The observation that disease-related proteins often interact with one another has motivated numerous network-based approaches for deciphering disease mechanisms. In particular, protein-protein interaction networks were successfully used to illuminate disease modules, i.e., interacting proteins working in concert to drive a disease. The identification of these modules can further our understanding of disease mechanisms. We devised a global method for the prediction of multiple disease modules simultaneously named GLADIATOR (GLobal Approach for DIsease AssociaTed mOdule Reconstruction). GLADIATOR relies on a gold-standard disease phenotypic similarity to obtain a pan-disease view of the underlying modules. To traverse the search space of potential disease modules, we applied a simulated annealing algorithm aimed at maximizing the correlation between module similarity and the gold-standard phenotypic similarity. Importantly, this optimization is employed over hundreds of diseases simultaneously. GLADIATOR's predicted modules highly agree with current knowledge about disease-related proteins. Furthermore, the modules exhibit high coherence with respect to functional annotations and are highly enriched with known curated pathways, outperforming previous methods. Examination of the predicted proteins shared by similar diseases demonstrates the diverse role of these proteins in mediating related processes across similar diseases. Last, we provide a detailed analysis of the suggested molecular mechanism predicted by GLADIATOR for hyperinsulinism, suggesting novel proteins involved in its pathology. GLADIATOR predicts disease modules by integrating knowledge of disease-related proteins and phenotypes across multiple diseases. The predicted modules are functionally coherent and are more in line with current biological knowledge compared to modules obtained using previous disease-centric methods. The source code for GLADIATOR can be downloaded from http://www.cs.tau.ac.il/~roded/GLADIATOR.zip .

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions

PubMed Central

Wagatsuma, Nobuhiko; Sakai, Ko

2017-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision. PMID:28163688

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions.

PubMed

Wagatsuma, Nobuhiko; Sakai, Ko

2016-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision.

Hydropedology: Synergistic integration of soil science and hydrology in the Critical Zone

USGS Publications Warehouse

Lin, H.S.; McDonnell, J.J.; Nimmo, John R.; Pachepsky, Y. A.

2016-01-01

Soil and water are the two critical components of theEarth’s Critical Zone (Figure 1): Soil modulates the connection between bedrock and the atmospheric boundary layer and water is a major driving force and transport agent between these two zones. The interactions between soil and water are so intimate and complex that they cannot be effectively studied in a piecemeal manner; they require a systems approach. In this spirit, hydropedology has emerged in recent years as a synergistic integration of soil science and hydrology that offers a renewed perspective and an integrated approach to understanding interactive pedologic and hydrologic processes and their properties in the Critical Zone.

MINE: Module Identification in Networks

PubMed Central

2011-01-01

Background Graphical models of network associations are useful for both visualizing and integrating multiple types of association data. Identifying modules, or groups of functionally related gene products, is an important challenge in analyzing biological networks. However, existing tools to identify modules are insufficient when applied to dense networks of experimentally derived interaction data. To address this problem, we have developed an agglomerative clustering method that is able to identify highly modular sets of gene products within highly interconnected molecular interaction networks. Results MINE outperforms MCODE, CFinder, NEMO, SPICi, and MCL in identifying non-exclusive, high modularity clusters when applied to the C. elegans protein-protein interaction network. The algorithm generally achieves superior geometric accuracy and modularity for annotated functional categories. In comparison with the most closely related algorithm, MCODE, the top clusters identified by MINE are consistently of higher density and MINE is less likely to designate overlapping modules as a single unit. MINE offers a high level of granularity with a small number of adjustable parameters, enabling users to fine-tune cluster results for input networks with differing topological properties. Conclusions MINE was created in response to the challenge of discovering high quality modules of gene products within highly interconnected biological networks. The algorithm allows a high degree of flexibility and user-customisation of results with few adjustable parameters. MINE outperforms several popular clustering algorithms in identifying modules with high modularity and obtains good overall recall and precision of functional annotations in protein-protein interaction networks from both S. cerevisiae and C. elegans. PMID:21605434

Spectrotemporal Processing in Spectral Tuning Modules of Cat Primary Auditory Cortex

PubMed Central

Atencio, Craig A.; Schreiner, Christoph E.

2012-01-01

Spectral integration properties show topographical order in cat primary auditory cortex (AI). Along the iso-frequency domain, regions with predominantly narrowly tuned (NT) neurons are segregated from regions with more broadly tuned (BT) neurons, forming distinct processing modules. Despite their prominent spatial segregation, spectrotemporal processing has not been compared for these regions. We identified these NT and BT regions with broad-band ripple stimuli and characterized processing differences between them using both spectrotemporal receptive fields (STRFs) and nonlinear stimulus/firing rate transformations. The durations of STRF excitatory and inhibitory subfields were shorter and the best temporal modulation frequencies were higher for BT neurons than for NT neurons. For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched, whereas for BT neurons it was not. Phase locking and feature selectivity were higher for NT neurons. Properties of the nonlinearities showed only slight differences across the bandwidth modules. These results indicate fundamental differences in spectrotemporal preferences - and thus distinct physiological functions - for neurons in BT and NT spectral integration modules. However, some global processing aspects, such as spectrotemporal interactions and nonlinear input/output behavior, appear to be similar for both neuronal subgroups. The findings suggest that spectral integration modules in AI differ in what specific stimulus aspects are processed, but they are similar in the manner in which stimulus information is processed. PMID:22384036

Age-related audiovisual interactions in the superior colliculus of the rat.

PubMed

Costa, M; Piché, M; Lepore, F; Guillemot, J-P

2016-04-21

It is well established that multisensory integration is a functional characteristic of the superior colliculus that disambiguates external stimuli and therefore reduces the reaction times toward simple audiovisual targets in space. However, in a condition where a complex audiovisual stimulus is used, such as the optical flow in the presence of modulated audio signals, little is known about the processing of the multisensory integration in the superior colliculus. Furthermore, since visual and auditory deficits constitute hallmark signs during aging, we sought to gain some insight on whether audiovisual processes in the superior colliculus are altered with age. Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10-12 months) and aged (21-22 months) rats. Looming circular concentric sinusoidal (CCS) gratings were presented alone and in the presence of sinusoidally amplitude modulated white noise. In both groups of rats, two different audiovisual response interactions were encountered in the spatial domain: superadditive, and suppressive. In contrast, additive audiovisual interactions were found only in adult rats. Hence, superior colliculus audiovisual interactions were more numerous in adult rats (38%) than in aged rats (8%). These results suggest that intersensory interactions in the superior colliculus play an essential role in space processing toward audiovisual moving objects during self-motion. Moreover, aging has a deleterious effect on complex audiovisual interactions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Identifying candidate driver genes by integrative ovarian cancer genomics data

NASA Astrophysics Data System (ADS)

Lu, Xinguo; Lu, Jibo

2017-08-01

Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

Development, Implementation, and Assessment of Climate Curricular Materials for Introductory Undergraduates: Lessons Learned from the InTeGrate Project's Climate of Change Module

NASA Astrophysics Data System (ADS)

Walker, B.; Fadem, C. M.; Shellito, L. J.

2014-12-01

Designing climate change curricular materials suitable for wide adoption across institutions and academic disciplines (including those outside of the geosciences) requires collaboration among faculty at different types of institutions and consideration of a variety of student populations, learning styles, and course formats. The Interdisciplinary Teaching of Geoscience for a Sustainable Future (InTeGrate) project, an NSF STEP Center program, provides opportunities for faculty to develop 2-3 week teaching modules to engage students in understanding the intersections between geoscience topics and societal issues. From 2012-2014, a team of 3 faculty from a liberal arts college, comprehensive university, and community college developed, implemented, assessed, and revised a 2-3 week module for introductory undergraduates entitled "Climate of change: interactions and feedbacks between water, air, and ice". The module uses authentic atmosphere, ocean, and cryosphere data from several regions to illustrate how climate impacts human societies and that the climate system has interacting components complicated by feedbacks, uncertainties, and human behavioral decisions. Students also consider past and present human adaptations to climate fluctuations. The module was piloted in introductory geology, meteorology, and oceanography courses during the 2012-2013 academic year, during which time formative and summative assessments were administered and used to modify the curricular materials. We will provide an overview of the module's content, instructional strategies involved in implementing the module, and methods of formative and summative assessment. We will also report on lessons learned during the development, piloting, revision, and publishing process, the importance of fostering partnerships between faculty from different institution types, and design approaches that promote widespread adoption of climate curricular materials.

The interactions of multisensory integration with endogenous and exogenous attention

PubMed Central

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-01-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

The interactions of multisensory integration with endogenous and exogenous attention.

PubMed

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-02-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

PubMed

Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

2014-11-20

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

The AC photovoltaic module is here!

NASA Astrophysics Data System (ADS)

Strong, Steven J.; Wohlgemuth, John H.; Wills, Robert H.

1997-02-01

This paper describes the design, development, and performance results of a large-area photovoltaic module whose electrical output is ac power suitable for direct connection to the utility grid. The large-area ac PV module features a dedicated, integrally mounted, high-efficiency dc-to-ac power inverter with a nominal output of 250 watts (STC) at 120 Vac, 60 H, that is fully compatible with utility power. The module's output is connected directly to the building's conventional ac distribution system without need for any dc wiring, string combiners, dc ground-fault protection or additional power-conditioning equipment. With its advantages, the ac photovoltaic module promises to become a universal building block for use in all utility-interactive PV systems. This paper discusses AC Module design aspects and utility interface issues (including islanding).

The integration of an online module on student learning.

PubMed

Yehle, Karen S; Chang, Karen

2012-11-01

Heart failure is a prevalent and costly condition. Patients with better self-management are less likely to be rehospitalized. An online interactive heart failure module was developed and integrated into a medical-surgical nursing course to assist students in learning how to care for patients with heart failure. The purpose of this study was to examine whether the integration of an online heart failure module improved baccalaureate nursing students' heart failure self-management knowledge. A pretest/posttest design was used to examine the effects of student knowledge of heart failure self-management following implementation of an online module. Among 235 students, significant improvement of heart failure self-management knowledge was observed (P < .05). The mean posttest scores ranged from 13.82 to 15.93. Students had problems mastering knowledge of weight monitoring, use of nonsteroidal anti-inflammatory drugs, symptoms to report to physicians, and potassium-based salt substitutes. These findings were similar to four studies examining nurses' knowledge of heart failure. Students and nurses have difficulty mastering similar heart failure education concepts. An additional strategy, such as simulated or case scenarios, needs to be developed to help nurses and nursing students master all key concepts of heart failure self-management.

Integrated systems analysis reveals a molecular network underlying autism spectrum disorders

PubMed Central

Li, Jingjing; Shi, Minyi; Ma, Zhihai; Zhao, Shuchun; Euskirchen, Ghia; Ziskin, Jennifer; Urban, Alexander; Hallmayer, Joachim; Snyder, Michael

2014-01-01

Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. PMID:25549968

Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

PubMed Central

Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

2015-01-01

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

Mothers' multimodal information processing is modulated by multimodal interactions with their infants.

PubMed

Tanaka, Yukari; Fukushima, Hirokata; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

2014-10-17

Social learning in infancy is known to be facilitated by multimodal (e.g., visual, tactile, and verbal) cues provided by caregivers. In parallel with infants' development, recent research has revealed that maternal neural activity is altered through interaction with infants, for instance, to be sensitive to infant-directed speech (IDS). The present study investigated the effect of mother- infant multimodal interaction on maternal neural activity. Event-related potentials (ERPs) of mothers were compared to non-mothers during perception of tactile-related words primed by tactile cues. Only mothers showed ERP modulation when tactile cues were incongruent with the subsequent words, and only when the words were delivered with IDS prosody. Furthermore, the frequency of mothers' use of those words was correlated with the magnitude of ERP differentiation between congruent and incongruent stimuli presentations. These results suggest that mother-infant daily interactions enhance multimodal integration of the maternal brain in parenting contexts.

Multisensory effects on somatosensation: a trimodal visuo-vestibular-tactile interaction

PubMed Central

Kaliuzhna, Mariia; Ferrè, Elisa Raffaella; Herbelin, Bruno; Blanke, Olaf; Haggard, Patrick

2016-01-01

Vestibular information about self-motion is combined with other sensory signals. Previous research described both visuo-vestibular and vestibular-tactile bilateral interactions, but the simultaneous interaction between all three sensory modalities has not been explored. Here we exploit a previously reported visuo-vestibular integration to investigate multisensory effects on tactile sensitivity in humans. Tactile sensitivity was measured during passive whole body rotations alone or in conjunction with optic flow, creating either purely vestibular or visuo-vestibular sensations of self-motion. Our results demonstrate that tactile sensitivity is modulated by perceived self-motion, as provided by a combined visuo-vestibular percept, and not by the visual and vestibular cues independently. We propose a hierarchical multisensory interaction that underpins somatosensory modulation: visual and vestibular cues are first combined to produce a multisensory self-motion percept. Somatosensory processing is then enhanced according to the degree of perceived self-motion. PMID:27198907

Mothers' multimodal information processing is modulated by multimodal interactions with their infants

PubMed Central

Tanaka, Yukari; Fukushima, Hirokata; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

2014-01-01

Social learning in infancy is known to be facilitated by multimodal (e.g., visual, tactile, and verbal) cues provided by caregivers. In parallel with infants' development, recent research has revealed that maternal neural activity is altered through interaction with infants, for instance, to be sensitive to infant-directed speech (IDS). The present study investigated the effect of mother- infant multimodal interaction on maternal neural activity. Event-related potentials (ERPs) of mothers were compared to non-mothers during perception of tactile-related words primed by tactile cues. Only mothers showed ERP modulation when tactile cues were incongruent with the subsequent words, and only when the words were delivered with IDS prosody. Furthermore, the frequency of mothers' use of those words was correlated with the magnitude of ERP differentiation between congruent and incongruent stimuli presentations. These results suggest that mother-infant daily interactions enhance multimodal integration of the maternal brain in parenting contexts. PMID:25322936

Passport-PeopleSoft integration for HANDI 2000 business management system

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

Wilson, D.

The integration between the PeopleSoft applications and Passport modules are accomplished with an off the shelf package developed by lNDUS. The product was updated to the PeopleSoft Release 7.O. The Integration product interacts with data from multiple products within Passport and PeopleSoft. For 10/l/98 the Integration will interlace between the following: (1) PassPort Accounts Payable, Contract Management, Inventory Management, Purchasing; and (2) PeopleSoft General Ledger, Project Costing, Human Resources, Payroll. The current supply systems and financial systems interact with each other via multiple custom interfaces. Data integrity and Y2K issues were some of the driving factors in replacement of thesemore » systems. The new systems allow FDH the opportunity to change the current business processes to go to a best business practice that the commercial off the shelf software was adopted.« less

A reconfigurable multicarrier demodulator architecture

NASA Technical Reports Server (NTRS)

Kwatra, S. C.; Jamali, M. M.

1991-01-01

An architecture based on parallel and pipline design approaches has been developed for the Frequency Division Multiple Access/Time Domain Multiplexed (FDMA/TDM) conversion system. The architecture has two main modules namely the transmultiplexer and the demodulator. The transmultiplexer has two pipelined modules. These are the shared multiplexed polyphase filter and the Fast Fourier Transform (FFT). The demodulator consists of carrier, clock, and data recovery modules which are interactive. Progress on the design of the MultiCarrier Demodulator (MCD) using commercially available chips and Application Specific Integrated Circuits (ASIC) and simulation studies using Viewlogic software will be presented at the conference.

Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans.

PubMed

Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

2012-02-01

Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α(2)-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gα(o). In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of 'inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α(2)-adrenoreceptors on afferent nociceptors and stimulatory α(1)-receptors on inhibitory peptidergic interneurons.

Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans

PubMed Central

Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

2012-01-01

Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α2-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gαo. In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of ‘inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α2-adrenoreceptors on afferent nociceptors and stimulatory α1-receptors on inhibitory peptidergic interneurons. PMID:22124329

A clinical database management system for improved integration of the Veterans Affairs Hospital Information System.

PubMed

Andrews, R D; Beauchamp, C

1989-12-01

The Department of Veterans Affairs (VA) Decentralized Hospital Computer Program (DHCP) contains data modules derived from separate ancillary services (e.g., Lab, Pharmacy and Radiology). It is currently difficult to integrate information between the modules. A prototype is being developed aimed at integrating ancillary data by storing clinical data oriented to the patient so that there is easy interaction of data from multiple services. A set of program utilities provides for user-defined functions of decision support, queries, and reports. Information can be used to monitor quality of care by providing feedback in the form of reports, and reminders. Initial testing has indicated the prototype's design and implementation are feasible (in terms of space requirements, speed, and ease of use) in outpatient and inpatient settings. The design, development, and clinical use of this prototype are described.

The condition-dependent transcriptional network in Escherichia coli.

PubMed

Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; Monsieurs, Pieter; De Moor, Bart; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen

2009-03-01

Thanks to the availability of high-throughput omics data, bioinformatics approaches are able to hypothesize thus-far undocumented genetic interactions. However, due to the amount of noise in these data, inferences based on a single data source are often unreliable. A popular approach to overcome this problem is to integrate different data sources. In this study, we describe DISTILLER, a novel framework for data integration that simultaneously analyzes microarray and motif information to find modules that consist of genes that are co-expressed in a subset of conditions, and their corresponding regulators. By applying our method on publicly available data, we evaluated the condition-specific transcriptional network of Escherichia coli. DISTILLER confirmed 62% of 736 interactions described in RegulonDB, and 278 novel interactions were predicted.

Towards integration of clinical decision support in commercial hospital information systems using distributed, reusable software and knowledge components.

PubMed

Müller, M L; Ganslandt, T; Eich, H P; Lang, K; Ohmann, C; Prokosch, H U

2001-12-01

Clinicians' acceptance of clinical decision support depends on its workflow-oriented, context-sensitive accessibility and availability at the point of care, integrated into the Electronic Patient Record (EPR). Commercially available Hospital Information Systems (HIS) often focus on administrative tasks and mostly do not provide additional knowledge based functionality. Their traditionally monolithic and closed software architecture encumbers integration of and interaction with external software modules. Our aim was to develop methods and interfaces to integrate knowledge sources into two different commercial hospital information systems to provide the best decision support possible within the context of available patient data. An existing, proven standalone scoring system for acute abdominal pain was supplemented by a communication interface. In both HIS we defined data entry forms and developed individual and reusable mechanisms for data exchange with external software modules. We designed an additional knowledge support frontend which controls data exchange between HIS and the knowledge modules. Finally, we added guidelines and algorithms to the knowledge library. Despite some major drawbacks which resulted mainly from the HIS' closed software architectures we showed exemplary, how external knowledge support can be integrated almost seamlessly into different commercial HIS. This paper describes the prototypical design and current implementation and discusses our experiences.

A model for the use of blended learning in large group teaching sessions.

PubMed

Herbert, Cristan; Velan, Gary M; Pryor, Wendy M; Kumar, Rakesh K

2017-11-09

Although blended learning has the potential to enhance the student experience, both in terms of engagement and flexibility, it can be difficult to effectively restructure existing courses. To achieve these goals for an introductory Pathology course, offered to more than 250 undergraduate students at UNSW Sydney, we devised a novel approach. For each topic presented over 2-3 weeks, a single face-to-face overview lecture was retained. The remaining content that had previously been delivered as conventional lectures was converted into short (12-18 min) online modules. These were based on lecture slides with added animations/highlights, plus narration using edited excerpts of previous lecture recordings. The modules also incorporated interactive questions and review quizzes with feedback which used various question types. Modules were developed in PowerPoint and iSpring and uploaded to Moodle as SCORM packages. Each topic concluded with an interactive large-group session focussing on integration of the content, with in-class questions to which students could respond via the Echo360 Active Learning Platform (ALP). Overall, more than 50% of face-to-face lecture time was replaced by online modules and interactive large-group sessions. Quantitative evaluation data included usage statistics from 264 students and feedback via online survey responses from 41 students. Qualitative evaluation data consisted of reflective commentaries from 160 student ePortfolios, which were analysed to identify factors affecting learning benefits and user acceptability. All of the modules were completed by 74% of students and on average, 83.1% of students eventually passed the optional review quizzes. Notably, 88.4% of students responded to in-class questions during the integration and feedback sessions via the ALP. Student reflections emphasised that the modules promoted understanding, which was reinforced through active learning. The modules were described as enjoyable, motivating and were appreciated for their flexibility, which enabled students to work at their own pace. In transforming this introductory Pathology course, we have demonstrated a model for the use of blended learning in large group teaching sessions, which achieved high levels of completion, satisfaction and value for learning.

Integrating Multimedia Techniques into CS Pedagogy.

ERIC Educational Resources Information Center

Adams, Sandra Honda; Jou, Richard; Nasri, Ahmad; Radimsky, Anne-Louise; Sy, Bon K.

Through its grants, the National Science Foundation sponsors workshops that inform faculty of current topics in computer science. Such a workshop, entitled, "Developing Multimedia-based Interactive Laboratory Modules for Computer Science," was given July 27-August 6, 1998, at Illinois State University at Normal. Each participant was…

Interaction Between Spatial and Feature Attention in Posterior Parietal Cortex

PubMed Central

Ibos, Guilhem; Freedman, David J.

2016-01-01

Summary Lateral intraparietal (LIP) neurons encode a vast array of sensory and cognitive variables. Recently, we proposed that the flexibility of feature representations in LIP reflect the bottom-up integration of sensory signals, modulated by feature-based attention (FBA), from upstream feature-selective cortical neurons. Moreover, LIP activity is also strongly modulated by the position of space-based attention (SBA). However, the mechanisms by which SBA and FBA interact to facilitate the representation of task-relevant spatial and non-spatial features in LIP remain unclear. We recorded from LIP neurons during performance of a task which required monkeys to detect specific conjunctions of color, motion-direction, and stimulus position. Here we show that FBA and SBA potentiate each other’s effect in a manner consistent with attention gating the flow of visual information along the cortical visual pathway. Our results suggest that linear bottom-up integrative mechanisms allow LIP neurons to emphasize task-relevant spatial and non-spatial features. PMID:27499082

Interaction between Spatial and Feature Attention in Posterior Parietal Cortex.

PubMed

Ibos, Guilhem; Freedman, David J

2016-08-17

Lateral intraparietal (LIP) neurons encode a vast array of sensory and cognitive variables. Recently, we proposed that the flexibility of feature representations in LIP reflect the bottom-up integration of sensory signals, modulated by feature-based attention (FBA), from upstream feature-selective cortical neurons. Moreover, LIP activity is also strongly modulated by the position of space-based attention (SBA). However, the mechanisms by which SBA and FBA interact to facilitate the representation of task-relevant spatial and non-spatial features in LIP remain unclear. We recorded from LIP neurons during performance of a task that required monkeys to detect specific conjunctions of color, motion direction, and stimulus position. Here we show that FBA and SBA potentiate each other's effect in a manner consistent with attention gating the flow of visual information along the cortical visual pathway. Our results suggest that linear bottom-up integrative mechanisms allow LIP neurons to emphasize task-relevant spatial and non-spatial features. Copyright © 2016 Elsevier Inc. All rights reserved.

Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution

NASA Astrophysics Data System (ADS)

Pani, R.; Gonzalez, A. J.; Bettiol, M.; Fabbri, A.; Cinti, M. N.; Preziosi, E.; Borrazzo, C.; Conde, P.; Pellegrini, R.; Di Castro, E.; Majewski, S.

2015-06-01

The proposal of Mindview European Project concerns with the development of a very high resolution and high efficiency brain dedicated PET scanner simultaneously working with a Magnetic Resonance scanner, that expects to visualize neurotransmitter pathways and their disruptions in the quest to better diagnose schizophrenia. On behalf of this project, we propose a low cost PET module for the first prototype, based on monolithic crystals, suitable to be integrated with a head Radio Frequency (RF) coil. The aim of the suggested module is to achieve high performances in terms of efficiency, planar spatial resolution (expected about 1 mm) and discrimination of gamma Depth Of Interaction (DOI) in order to reduce the parallax error. Our preliminary results are very promising: a DOI resolution of about 3 mm, a spatial resolution ranging from about 1 to 1.5 mm and a good position linearity.

Bayesian module identification from multiple noisy networks.

PubMed

Zamani Dadaneh, Siamak; Qian, Xiaoning

2016-12-01

Module identification has been studied extensively in order to gain deeper understanding of complex systems, such as social networks as well as biological networks. Modules are often defined as groups of vertices in these networks that are topologically cohesive with similar interaction patterns with the rest of the vertices. Most of the existing module identification algorithms assume that the given networks are faithfully measured without errors. However, in many real-world applications, for example, when analyzing protein-protein interaction networks from high-throughput profiling techniques, there is significant noise with both false positive and missing links between vertices. In this paper, we propose a new model for more robust module identification by taking advantage of multiple observed networks with significant noise so that signals in multiple networks can be strengthened and help improve the solution quality by combining information from various sources. We adopt a hierarchical Bayesian model to integrate multiple noisy snapshots that capture the underlying modular structure of the networks under study. By introducing a latent root assignment matrix and its relations to instantaneous module assignments in all the observed networks to capture the underlying modular structure and combine information across multiple networks, an efficient variational Bayes algorithm can be derived to accurately and robustly identify the underlying modules from multiple noisy networks. Experiments on synthetic and protein-protein interaction data sets show that our proposed model enhances both the accuracy and resolution in detecting cohesive modules, and it is less vulnerable to noise in the observed data. In addition, it shows higher power in predicting missing edges compared to individual-network methods.

A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

PubMed Central

Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

Theta-Modulated Gamma-Band Synchronization Among Activated Regions During a Verb Generation Task

PubMed Central

Doesburg, Sam M.; Vinette, Sarah A.; Cheung, Michael J.; Pang, Elizabeth W.

2012-01-01

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4–8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing. PMID:22707946

Functional Module Search in Protein Networks based on Semantic Similarity Improves the Analysis of Proteomics Data*

PubMed Central

Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W.; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

2014-01-01

The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

PubMed Central

Hedger, George; Sansom, Mark S. P.

2017-01-01

Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterisation of these sites is of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. PMID:26946244

Effects of light touch on postural sway and visual search accuracy: A test of functional integration and resource competition hypotheses.

PubMed

Chen, Fu-Chen; Chen, Hsin-Lin; Tu, Jui-Hung; Tsai, Chia-Liang

2015-09-01

People often multi-task in their daily life. However, the mechanisms for the interaction between simultaneous postural and non-postural tasks have been controversial over the years. The present study investigated the effects of light digital touch on both postural sway and visual search accuracy for the purpose of assessing two hypotheses (functional integration and resource competition), which may explain the interaction between postural sway and the performance of a non-postural task. Participants (n=42, 20 male and 22 female) were asked to inspect a blank sheet of paper or visually search for target letters in a text block while a fingertip was in light contact with a stable surface (light touch, LT), or with both arms hanging at the sides of the body (no touch, NT). The results showed significant main effects of LT on reducing the magnitude of postural sway as well as enhancing visual search accuracy compared with the NT condition. The findings support the hypothesis of function integration, demonstrating that the modulation of postural sway can be modulated to improve the performance of a visual search task. Copyright © 2015 Elsevier B.V. All rights reserved.

Astrophysics-independent bounds on the annual modulation of dark matter signals.

PubMed

Herrero-Garcia, Juan; Schwetz, Thomas; Zupan, Jure

2012-10-05

We show how constraints on the time integrated event rate from a given dark matter (DM) direct detection experiment can be used to bound the amplitude of the annual modulation signal in another experiment. The method requires only mild assumptions about the properties of the local DM distribution: that it is temporally stable on the scale of months and spatially homogeneous on the ecliptic. We apply the method to the annual modulation signal in DAMA/LIBRA, which we compare to the bounds derived from XENON10, XENON100, cryogenic DM search, and SIMPLE data. Assuming a DM mass of 10 GeV, we show that under the above assumptions about the DM halo, a DM interpretation of the DAMA/LIBRA signal is excluded for several classes of models: at 6.3σ (4.6σ) for elastic isospin conserving (violating) spin-independent interactions, and at 4.9σ for elastic spin-dependent interactions on protons.

Design of Instrument Control Software for Solar Vector Magnetograph at Udaipur Solar Observatory

NASA Astrophysics Data System (ADS)

Gosain, Sanjay; Venkatakrishnan, P.; Venugopalan, K.

2004-04-01

A magnetograph is an instrument which makes measurement of solar magnetic field by measuring Zeeman induced polarization in solar spectral lines. In a typical filter based magnetograph there are three main modules namely, polarimeter, narrow-band spectrometer (filter), and imager(CCD camera). For a successful operation of magnetograph it is essential that these modules work in synchronization with each other. Here, we describe the design of instrument control system implemented for the Solar Vector Magnetograph under development at Udaipur Solar Observatory. The control software is written in Visual Basic and exploits the Component Object Model (COM) components for a fast and flexible application development. The user can interact with the instrument modules through a Graphical User Interface (GUI) and can program the sequence of magnetograph operations. The integration of Interactive Data Language (IDL) ActiveX components in the interface provides a powerful tool for online visualization, analysis and processing of images.

Biomass and fire dynamics in a temperate forest-grassland mosaic: Integrating multi-species herbivory, climate, and fire with the FireBGCv2/GrazeBGC system

Treesearch

Robert A. Riggs; Robert E. Keane; Norm Cimon; Rachel Cook; Lisa Holsinger; John Cook; Timothy DelCurto; L.Scott Baggett; Donald Justice; David Powell; Martin Vavra; Bridgett Naylor

2015-01-01

Landscape fire succession models (LFSMs) predict spatially-explicit interactions between vegetation succession and disturbance, but these models have yet to fully integrate ungulate herbivory as a driver of their processes. We modified a complex LFSM, FireBGCv2, to include a multi-species herbivory module, GrazeBGC. The system is novel in that it explicitly...

How bodies and voices interact in early emotion perception.

PubMed

Jessen, Sarah; Obleser, Jonas; Kotz, Sonja A

2012-01-01

Successful social communication draws strongly on the correct interpretation of others' body and vocal expressions. Both can provide emotional information and often occur simultaneously. Yet their interplay has hardly been studied. Using electroencephalography, we investigated the temporal development underlying their neural interaction in auditory and visual perception. In particular, we tested whether this interaction qualifies as true integration following multisensory integration principles such as inverse effectiveness. Emotional vocalizations were embedded in either low or high levels of noise and presented with or without video clips of matching emotional body expressions. In both, high and low noise conditions, a reduction in auditory N100 amplitude was observed for audiovisual stimuli. However, only under high noise, the N100 peaked earlier in the audiovisual than the auditory condition, suggesting facilitatory effects as predicted by the inverse effectiveness principle. Similarly, we observed earlier N100 peaks in response to emotional compared to neutral audiovisual stimuli. This was not the case in the unimodal auditory condition. Furthermore, suppression of beta-band oscillations (15-25 Hz) primarily reflecting biological motion perception was modulated 200-400 ms after the vocalization. While larger differences in suppression between audiovisual and audio stimuli in high compared to low noise levels were found for emotional stimuli, no such difference was observed for neutral stimuli. This observation is in accordance with the inverse effectiveness principle and suggests a modulation of integration by emotional content. Overall, results show that ecologically valid, complex stimuli such as joined body and vocal expressions are effectively integrated very early in processing.

Target-object integration, attention distribution, and object orientation interactively modulate object-based selection.

PubMed

Al-Janabi, Shahd; Greenberg, Adam S

2016-10-01

The representational basis of attentional selection can be object-based. Various studies have suggested, however, that object-based selection is less robust than spatial selection across experimental paradigms. We sought to examine the manner by which the following factors might explain this variation: Target-Object Integration (targets 'on' vs. part 'of' an object), Attention Distribution (narrow vs. wide), and Object Orientation (horizontal vs. vertical). In Experiment 1, participants discriminated between two targets presented 'on' an object in one session, or presented as a change 'of' an object in another session. There was no spatial cue-thus, attention was initially focused widely-and the objects were horizontal or vertical. We found evidence of object-based selection only when targets constituted a change 'of' an object. Additionally, object orientation modulated the sign of object-based selection: We observed a same-object advantage for horizontal objects, but a same-object cost for vertical objects. In Experiment 2, an informative cue preceded a single target presented 'on' an object or as a change 'of' an object (thus, attention was initially focused narrowly). Unlike in Experiment 1, we found evidence of object-based selection independent of target-object integration. We again found that the sign of selection was modulated by the objects' orientation. This result may reflect a meridian effect, which emerged due to anisotropies in the cortical representations when attention is oriented endogenously. Experiment 3 revealed that object orientation did not modulate object-based selection when attention was oriented exogenously. Our findings suggest that target-object integration, attention distribution, and object orientation modulate object-based selection, but only in combination.

Optical solitons and modulation instability analysis of an integrable model of (2+1)-Dimensional Heisenberg ferromagnetic spin chain equation

NASA Astrophysics Data System (ADS)

Inc, Mustafa; Aliyu, Aliyu Isa; Yusuf, Abdullahi; Baleanu, Dumitru

2017-12-01

This paper addresses the nonlinear Schrödinger type equation (NLSE) in (2+1)-dimensions which describes the nonlinear spin dynamics of Heisenberg ferromagnetic spin chains (HFSC) with anisotropic and bilinear interactions in the semiclassical limit. Two integration schemes are employed to study the equation. These are the complex envelope function ansatz and the generalized tanh methods. Dark, dark-bright or combined optical and singular soliton solutions of the equation are derived. Furthermore, the modulational instability (MI) is studied based on the standard linear-stability analysis and the MI gain is got. Numerical simulation of the obtained results are analyzed with interesting figures showing the physical meaning of the solutions.

Integrated regulatory network reveals novel candidate regulators in the development of negative energy balance in cattle.

PubMed

Mozduri, Z; Bakhtiarizadeh, M R; Salehi, A

2018-06-01

Negative energy balance (NEB) is an altered metabolic state in modern high-yielding dairy cows. This metabolic state occurs in the early postpartum period when energy demands for milk production and maintenance exceed that of energy intake. Negative energy balance or poor adaptation to this metabolic state has important effects on the liver and can lead to metabolic disorders and reduced fertility. The roles of regulatory factors, including transcription factors (TFs) and micro RNAs (miRNAs) have often been separately studied for evaluating of NEB. However, adaptive response to NEB is controlled by complex gene networks and still not fully understood. In this study, we aimed to discover the integrated gene regulatory networks involved in NEB development in liver tissue. We downloaded data sets including mRNA and miRNA expression profiles related to three and four cows with severe and moderate NEB, respectively. Our method integrated two independent types of information: module inference network by TFs, miRNAs and mRNA expression profiles (RNA-seq data) and computational target predictions. In total, 176 modules were predicted by using gene expression data and 64 miRNAs and 63 TFs were assigned to these modules. By using our integrated computational approach, we identified 13 TF-module and 19 miRNA-module interactions. Most of these modules were associated with liver metabolic processes as well as immune and stress responses, which might play crucial roles in NEB development. Literature survey results also showed that several regulators and gene targets have already been characterized as important factors in liver metabolic processes. These results provided novel insights into regulatory mechanisms at the TF and miRNA levels during NEB. In addition, the method described in this study seems to be applicable to construct integrated regulatory networks for different diseases or disorders.

BioInt: an integrative biological object-oriented application framework and interpreter.

PubMed

Desai, Sanket; Burra, Prasad

2015-01-01

BioInt, a biological programming application framework and interpreter, is an attempt to equip the researchers with seamless integration, efficient extraction and effortless analysis of the data from various biological databases and algorithms. Based on the type of biological data, algorithms and related functionalities, a biology-specific framework was developed which has nine modules. The modules are a compilation of numerous reusable BioADTs. This software ecosystem containing more than 450 biological objects underneath the interpreter makes it flexible, integrative and comprehensive. Similar to Python, BioInt eliminates the compilation and linking steps cutting the time significantly. The researcher can write the scripts using available BioADTs (following C++ syntax) and execute them interactively or use as a command line application. It has features that enable automation, extension of the framework with new/external BioADTs/libraries and deployment of complex work flows.

Top-down modulation: the crossroads of perception, attention and memory

NASA Astrophysics Data System (ADS)

Gazzaley, Adam

2010-02-01

Research in our laboratory focuses on understanding the neural mechanisms that serve at the crossroads of perception, memory and attention, specifically exploring how brain region interactions underlie these abilities. To accomplish this, we study top-down modulation, the process by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information, thus establishing a neural basis for all higher-order cognitive operations. We also study alterations in top-down modulation that occur with normal aging. Our experiments are performed on human participants, using a multimodal approach that integrates functional MRI (fMRI), transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

Modular neuron-based body estimation: maintaining consistency over different limbs, modalities, and frames of reference

PubMed Central

Ehrenfeld, Stephan; Herbort, Oliver; Butz, Martin V.

2013-01-01

This paper addresses the question of how the brain maintains a probabilistic body state estimate over time from a modeling perspective. The neural Modular Modality Frame (nMMF) model simulates such a body state estimation process by continuously integrating redundant, multimodal body state information sources. The body state estimate itself is distributed over separate, but bidirectionally interacting modules. nMMF compares the incoming sensory and present body state information across the interacting modules and fuses the information sources accordingly. At the same time, nMMF enforces body state estimation consistency across the modules. nMMF is able to detect conflicting sensory information and to consequently decrease the influence of implausible sensor sources on the fly. In contrast to the previously published Modular Modality Frame (MMF) model, nMMF offers a biologically plausible neural implementation based on distributed, probabilistic population codes. Besides its neural plausibility, the neural encoding has the advantage of enabling (a) additional probabilistic information flow across the separate body state estimation modules and (b) the representation of arbitrary probability distributions of a body state. The results show that the neural estimates can detect and decrease the impact of false sensory information, can propagate conflicting information across modules, and can improve overall estimation accuracy due to additional module interactions. Even bodily illusions, such as the rubber hand illusion, can be simulated with nMMF. We conclude with an outlook on the potential of modeling human data and of invoking goal-directed behavioral control. PMID:24191151

Miniaturized sensor module for a mechatronic bearing

NASA Astrophysics Data System (ADS)

Gao, Robert X.; Sahay, Priyaranjan

1998-12-01

To assess the working condition of a rolling element bearing, the condition monitoring system should be located as close as possible to the bearing to take advantage of shorter signal transmission path, increased signal-to-noise ratio, and reduced complexity of the signal processing electronics. The advantages of integrated sensing are presented in this paper, with a focus on the design and analysis of a miniaturized sensor module. Mechatronic principles have been applied to treat the various subjects in a synergistic way. To complement analytical studies, experiments have been conducted on a scaled-up version of the sensor module to analyze the system dynamic response. The result obtained provided insight into the electromechanical interaction within the module as well as input for the system implementation using miniaturization technologies.

A Module on Death and Dying to Develop Empathy in Student Pharmacists

PubMed Central

Olin, Jacqueline L.; Thornton, Phillip L.; Dolder, Christian R.; Hanrahan, Conor

2011-01-01

Objective To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists’ empathy. Design Students participated in a 5-week death and dying module that included presentation of the film Wit, an interactive lecture on hospice, and a lecture on the ethics of pain management. Assessment Fifty-six students completed the 30-item Balanced Emotional Empathy Scale (BEES) before and after completing the module and wrote a reflective essay. Students demonstrated an appreciation of patient-specific values in their essay. Quantitative data collected via BEES scores demonstrated significant improvement in measured empathy. Conclusion A 5-week instructional model on death and dying significantly increased student empathy. PMID:21769147

Functional cortical network in alpha band correlates with social bargaining.

PubMed

Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals' alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts.

Functional Cortical Network in Alpha Band Correlates with Social Bargaining

PubMed Central

Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals’ alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts. PMID:25286240

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Pgltools: a genomic arithmetic tool suite for manipulation of Hi-C peak and other chromatin interaction data.

PubMed

Greenwald, William W; Li, He; Smith, Erin N; Benaglio, Paola; Nariai, Naoki; Frazer, Kelly A

2017-04-07

Genomic interaction studies use next-generation sequencing (NGS) to examine the interactions between two loci on the genome, with subsequent bioinformatics analyses typically including annotation, intersection, and merging of data from multiple experiments. While many file types and analysis tools exist for storing and manipulating single locus NGS data, there is currently no file standard or analysis tool suite for manipulating and storing paired-genomic-loci: the data type resulting from "genomic interaction" studies. As genomic interaction sequencing data are becoming prevalent, a standard file format and tools for working with these data conveniently and efficiently are needed. This article details a file standard and novel software tool suite for working with paired-genomic-loci data. We present the paired-genomic-loci (PGL) file standard for genomic-interactions data, and the accompanying analysis tool suite "pgltools": a cross platform, pypy compatible python package available both as an easy-to-use UNIX package, and as a python module, for integration into pipelines of paired-genomic-loci analyses. Pgltools is a freely available, open source tool suite for manipulating paired-genomic-loci data. Source code, an in-depth manual, and a tutorial are available publicly at www.github.com/billgreenwald/pgltools , and a python module of the operations can be installed from PyPI via the PyGLtools module.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

PubMed

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas ( e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang ). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

PubMed Central

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses. PMID:29403392

How music alters a kiss: superior temporal gyrus controls fusiform-amygdalar effective connectivity.

PubMed

Pehrs, Corinna; Deserno, Lorenz; Bakels, Jan-Hendrik; Schlochtermeier, Lorna H; Kappelhoff, Hermann; Jacobs, Arthur M; Fritz, Thomas Hans; Koelsch, Stefan; Kuchinke, Lars

2014-11-01

While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform-amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

How music alters a kiss: superior temporal gyrus controls fusiform–amygdalar effective connectivity

PubMed Central

Deserno, Lorenz; Bakels, Jan-Hendrik; Schlochtermeier, Lorna H.; Kappelhoff, Hermann; Jacobs, Arthur M.; Fritz, Thomas Hans; Koelsch, Stefan; Kuchinke, Lars

2014-01-01

While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform–amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala. PMID:24298171

Integration of biological networks and gene expression data using Cytoscape

PubMed Central

Cline, Melissa S; Smoot, Michael; Cerami, Ethan; Kuchinsky, Allan; Landys, Nerius; Workman, Chris; Christmas, Rowan; Avila-Campilo, Iliana; Creech, Michael; Gross, Benjamin; Hanspers, Kristina; Isserlin, Ruth; Kelley, Ryan; Killcoyne, Sarah; Lotia, Samad; Maere, Steven; Morris, John; Ono, Keiichiro; Pavlovic, Vuk; Pico, Alexander R; Vailaya, Aditya; Wang, Peng-Liang; Adler, Annette; Conklin, Bruce R; Hood, Leroy; Kuiper, Martin; Sander, Chris; Schmulevich, Ilya; Schwikowski, Benno; Warner, Guy J; Ideker, Trey; Bader, Gary D

2013-01-01

Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape. PMID:17947979

Toward a community ecology of landscapes: predicting multiple predator-prey interactions across geographic space.

PubMed

Schmitz, Oswald J; Miller, Jennifer R B; Trainor, Anne M; Abrahms, Briana

2017-09-01

Community ecology was traditionally an integrative science devoted to studying interactions between species and their abiotic environments in order to predict species' geographic distributions and abundances. Yet for philosophical and methodological reasons, it has become divided into two enterprises: one devoted to local experimentation on species interactions to predict community dynamics; the other devoted to statistical analyses of abiotic and biotic information to describe geographic distribution. Our goal here is to instigate thinking about ways to reconnect the two enterprises and thereby return to a tradition to do integrative science. We focus specifically on the community ecology of predators and prey, which is ripe for integration. This is because there is active, simultaneous interest in experimentally resolving the nature and strength of predator-prey interactions as well as explaining patterns across landscapes and seascapes. We begin by describing a conceptual theory rooted in classical analyses of non-spatial food web modules used to predict species interactions. We show how such modules can be extended to consideration of spatial context using the concept of habitat domain. Habitat domain describes the spatial extent of habitat space that predators and prey use while foraging, which differs from home range, the spatial extent used by an animal to meet all of its daily needs. This conceptual theory can be used to predict how different spatial relations of predators and prey could lead to different emergent multiple predator-prey interactions such as whether predator consumptive or non-consumptive effects should dominate, and whether intraguild predation, predator interference or predator complementarity are expected. We then review the literature on studies of large predator-prey interactions that make conclusions about the nature of multiple predator-prey interactions. This analysis reveals that while many studies provide sufficient information about predator or prey spatial locations, and thus meet necessary conditions of the habitat domain conceptual theory for drawing conclusions about the nature of the predator-prey interactions, several studies do not. We therefore elaborate how modern technology and statistical approaches for animal movement analysis could be used to test the conceptual theory, using experimental or quasi-experimental analyses at landscape scales. © 2017 by the Ecological Society of America.

Integrated regulation of motor-driven organelle transport by scaffolding proteins.

PubMed

Fu, Meng-meng; Holzbaur, Erika L F

2014-10-01

Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-binding protein), JIP1, JIP3 (JNK-interacting proteins), huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins, including kinases and GTPases, to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

PubMed Central

Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N.; Jones, Byron C.; Lu, Lu; Wang, Xusheng

2018-01-01

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses. PMID:29674951

Blended Learning in a Teacher Training Course: Integrated Interactive E-Learning and Contact Learning

ERIC Educational Resources Information Center

Kupetz, Rita; Ziegenmeyer, Brigit

2005-01-01

The paper discusses a blended learning concept for a university teacher training course for prospective teachers of English. The concept aims at purposeful learning using different methods and activities, various traditional and electronic media, learning spaces covering contact and distance learning, and task-based learning modules that begin…

The interaction and integration of auxin signaling components.

PubMed

Hayashi, Ken-ichiro

2012-06-01

IAA, a naturally occurring auxin, is a simple signaling molecule that regulates many diverse steps of plant development. Auxin essentially coordinates plant development through transcriptional regulation. Auxin binds to TIR1/AFB nuclear receptors, which are F-box subunits of the SCF ubiquitin ligase complex. The auxin signal is then modulated by the quantitative and qualitative responses of the Aux/IAA repressors and the auxin response factor (ARF) transcription factors. The specificity of the auxin-regulated gene expression profile is defined by several factors, such as the expression of these regulatory proteins, their post-transcriptional regulation, their stability and the affinity between these regulatory proteins. Auxin-binding protein 1 (ABP1) is a candidate protein for an auxin receptor that is implicated in non-transcriptional auxin signaling. ABP1 also affects TIR1/AFB-mediated auxin-responsive gene expression, implying that both the ABP1 and TIR1/AFB signaling machineries coordinately control auxin-mediated physiological events. Systematic approaches using the comprehensive mapping of the expression and interaction of signaling modules and computational modeling would be valuable for integrating our knowledge of auxin signals and responses.

Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model

PubMed Central

Martin, Francois-Pierre J; Wang, Yulan; Sprenger, Norbert; Yap, Ivan K S; Rezzi, Serge; Ramadan, Ziad; Peré-Trepat, Emma; Rochat, Florence; Cherbut, Christine; van Bladeren, Peter; Fay, Laurent B; Kochhar, Sunil; Lindon, John C; Holmes, Elaine; Nicholson, Jeremy K

2008-01-01

Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ-free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co-administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino-acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis. PMID:18628745

Wound healing process and mediators: Implications for modulations for hernia repair and mesh integration.

PubMed

Sadava, Emmanuel E; Krpata, David M; Gao, Yue; Rosen, Michael J; Novitsky, Yuri W

2014-01-01

In recent years, major advances have been accomplished in abdominal wall reconstruction. Introduction of newer prostheses have improved outcomes, but elimination of mesh-related morbidity is still an elusive issue. It is believed that host foreign body reaction to prosthesis plays an important role in the biology of these complications, so understanding of the molecular mechanisms behind mesh-tissue interactions may be a key for upcoming therapies. It appears that increasing biocompatibility of both synthetic prosthesis and biologic scaffolds might be the main avenues to achieve better outcomes. This manuscript provides an overview of major effectors of wound healing with particular emphasis on how their modulation might improve outcomes in tissue remodeling and mesh integration. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Technology-Enhanced Learning in Science (TELS)

NASA Astrophysics Data System (ADS)

Linn, Marcia

2006-12-01

The overall research question addressed by the NSF-funded echnologyEnhanced Learning in Science (TELS) Center is whether interactive scientific visualizations embedded in high quality instructional units can be used to increase pre-college student learning in science. The research draws on the knowledge integration framework to guide the design of instructional modules, professional development activities, and assessment activities. This talk reports on results from the first year where 50 teachers taught one of the 12 TELS modules in over 200 classes in 16 diverse schools. Assessments scored with the knowledge integration rubric showed that students made progress in learning complex physics topics such as electricity, mechanics, and thermodynamics. Teachers encountered primarily technological obstacles that the research team was able to address prior to implementation. Powerful scientific visualizations required extensive instructional supports to communicate to students. Currently, TELS is refining the modules, professional development, and assessments based on evidence from the first year. Preliminary design principles intended to help research teams build on the findings will be presented for audience feedback and discussion.

40-Gb/s directly-modulated photonic crystal lasers under optical injection-locking

NASA Astrophysics Data System (ADS)

Chen, Chin-Hui; Takeda, Koji; Shinya, Akihiko; Nozaki, Kengo; Sato, Tomonari; Kawaguchi, Yoshihiro; Notomi, Masaya; Matsuo, Shinji

2011-08-01

CMOS integrated circuits (IC) usually requires high data bandwidth for off-chip input/output (I/O) data transport with sufficiently low power consumption in order to overcome pin-count limitation. In order to meet future requirements of photonic network interconnect, we propose an optical output device based on an optical injection-locked photonic crystal (PhC) laser to realize low-power and high-speed off-chip interconnects. This device enables ultralow-power operation and is suitable for highly integrated photonic circuits because of its strong light-matter interaction in the PhC nanocavity and ultra-compact size. High-speed operation is achieved by using the optical injection-locking (OIL) technique, which has been shown as an effective means to enhance modulation bandwidth beyond the relaxation resonance frequency limit. In this paper, we report experimental results of the OIL-PhC laser under various injection conditions and also demonstrate 40-Gb/s large-signal direct modulation with an ultralow energy consumption of 6.6 fJ/bit.

Hemodynamic (fNIRS) and EEG (N200) correlates of emotional inter-species interactions modulated by visual and auditory stimulation

PubMed Central

Balconi, Michela; Vanutelli, Maria Elide

2016-01-01

The brain activity, considered in its hemodynamic (optical imaging: functional Near-Infrared Spectroscopy, fNIRS) and electrophysiological components (event-related potentials, ERPs, N200) was monitored when subjects observed (visual stimulation, V) or observed and heard (visual + auditory stimulation, VU) situations which represented inter-species (human-animal) interactions, with an emotional positive (cooperative) or negative (uncooperative) content. In addition, the cortical lateralization effect (more left or right dorsolateral prefrontal cortex, DLPFC) was explored. Both ERP and fNIRS showed significant effects due to emotional interactions which were discussed at light of cross-modal integration effects. The significance of inter-species effect for the emotional behavior was considered. In addition, hemodynamic and EEG consonant results and their value as integrated measures were discussed at light of valence effect. PMID:26976052

The WEBD project: a research of new methodologies for a distant-learning 3D system prototype.

PubMed

Cemenasco, A F; Bianchi, C C; Tornincasa, S; Bianchi, S D

2004-11-01

To create and to spread a new interactive multimedia instrument, based upon virtual reality technologies, that allows both the running simulation of machines and equipment and the reproduction via Web of complex three-dimensional (3D) anatomical models such as the skull. There were two main aspects of the project, one of design engineering and the other biomedical engineering, for the creation of "artificial" and anatomical objects. The former were made with 3D Studio Max R4 by Autodesk, San Rafael, CA, while the latter were created starting from real bones scanned with a CT system or a surface scanner and elaborated with different programs (3D Studio Max R4, Scenebuilder by Viewpoint, New York, NY and Spinfire by Actify, San Francisco, CA). The 3D models were to be integrated into web modules and had to respect file limits while preserving a sufficient definition. Two systems of evaluation were used, a questionnaire on a selected sample and an external evaluation by a different university. The Viewpoint format offers the best interactivity and size reduction (up to 96% from the original 3D model). The created modules included production of radiological images, rapid prototyping, and anatomy. The complete "3D Distant Learning Prototype" is available at www.webd.etsii.upm.es. The software currently available permits the construction of interactive modules. The verification on the selected sample and the evaluation by the University of Naples show that the structure is well organized and that the integration of the 3D models meets the requirements.

Cardiorespiratory interactions in neural circulatory control in humans.

PubMed

Shamsuzzaman, A S; Somers, V K

2001-06-01

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

ePlant and the 3D data display initiative: integrative systems biology on the world wide web.

PubMed

Fucile, Geoffrey; Di Biase, David; Nahal, Hardeep; La, Garon; Khodabandeh, Shokoufeh; Chen, Yani; Easley, Kante; Christendat, Dinesh; Kelley, Lawrence; Provart, Nicholas J

2011-01-10

Visualization tools for biological data are often limited in their ability to interactively integrate data at multiple scales. These computational tools are also typically limited by two-dimensional displays and programmatic implementations that require separate configurations for each of the user's computing devices and recompilation for functional expansion. Towards overcoming these limitations we have developed "ePlant" (http://bar.utoronto.ca/eplant) - a suite of open-source world wide web-based tools for the visualization of large-scale data sets from the model organism Arabidopsis thaliana. These tools display data spanning multiple biological scales on interactive three-dimensional models. Currently, ePlant consists of the following modules: a sequence conservation explorer that includes homology relationships and single nucleotide polymorphism data, a protein structure model explorer, a molecular interaction network explorer, a gene product subcellular localization explorer, and a gene expression pattern explorer. The ePlant's protein structure explorer module represents experimentally determined and theoretical structures covering >70% of the Arabidopsis proteome. The ePlant framework is accessed entirely through a web browser, and is therefore platform-independent. It can be applied to any model organism. To facilitate the development of three-dimensional displays of biological data on the world wide web we have established the "3D Data Display Initiative" (http://3ddi.org).

Abiotic Stress Responses and Microbe-Mediated Mitigation in Plants: The Omics Strategies

PubMed Central

Meena, Kamlesh K.; Sorty, Ajay M.; Bitla, Utkarsh M.; Choudhary, Khushboo; Gupta, Priyanka; Pareek, Ashwani; Singh, Dhananjaya P.; Prabha, Ratna; Sahu, Pramod K.; Gupta, Vijai K.; Singh, Harikesh B.; Krishanani, Kishor K.; Minhas, Paramjit S.

2017-01-01

Abiotic stresses are the foremost limiting factors for agricultural productivity. Crop plants need to cope up adverse external pressure created by environmental and edaphic conditions with their intrinsic biological mechanisms, failing which their growth, development, and productivity suffer. Microorganisms, the most natural inhabitants of diverse environments exhibit enormous metabolic capabilities to mitigate abiotic stresses. Since microbial interactions with plants are an integral part of the living ecosystem, they are believed to be the natural partners that modulate local and systemic mechanisms in plants to offer defense under adverse external conditions. Plant-microbe interactions comprise complex mechanisms within the plant cellular system. Biochemical, molecular and physiological studies are paving the way in understanding the complex but integrated cellular processes. Under the continuous pressure of increasing climatic alterations, it now becomes more imperative to define and interpret plant-microbe relationships in terms of protection against abiotic stresses. At the same time, it also becomes essential to generate deeper insights into the stress-mitigating mechanisms in crop plants for their translation in higher productivity. Multi-omics approaches comprising genomics, transcriptomics, proteomics, metabolomics and phenomics integrate studies on the interaction of plants with microbes and their external environment and generate multi-layered information that can answer what is happening in real-time within the cells. Integration, analysis and decipherization of the big-data can lead to a massive outcome that has significant chance for implementation in the fields. This review summarizes abiotic stresses responses in plants in-terms of biochemical and molecular mechanisms followed by the microbe-mediated stress mitigation phenomenon. We describe the role of multi-omics approaches in generating multi-pronged information to provide a better understanding of plant–microbe interactions that modulate cellular mechanisms in plants under extreme external conditions and help to optimize abiotic stresses. Vigilant amalgamation of these high-throughput approaches supports a higher level of knowledge generation about root-level mechanisms involved in the alleviation of abiotic stresses in organisms. PMID:28232845

Abiotic Stress Responses and Microbe-Mediated Mitigation in Plants: The Omics Strategies.

PubMed

Meena, Kamlesh K; Sorty, Ajay M; Bitla, Utkarsh M; Choudhary, Khushboo; Gupta, Priyanka; Pareek, Ashwani; Singh, Dhananjaya P; Prabha, Ratna; Sahu, Pramod K; Gupta, Vijai K; Singh, Harikesh B; Krishanani, Kishor K; Minhas, Paramjit S

2017-01-01

Abiotic stresses are the foremost limiting factors for agricultural productivity. Crop plants need to cope up adverse external pressure created by environmental and edaphic conditions with their intrinsic biological mechanisms, failing which their growth, development, and productivity suffer. Microorganisms, the most natural inhabitants of diverse environments exhibit enormous metabolic capabilities to mitigate abiotic stresses. Since microbial interactions with plants are an integral part of the living ecosystem, they are believed to be the natural partners that modulate local and systemic mechanisms in plants to offer defense under adverse external conditions. Plant-microbe interactions comprise complex mechanisms within the plant cellular system. Biochemical, molecular and physiological studies are paving the way in understanding the complex but integrated cellular processes. Under the continuous pressure of increasing climatic alterations, it now becomes more imperative to define and interpret plant-microbe relationships in terms of protection against abiotic stresses. At the same time, it also becomes essential to generate deeper insights into the stress-mitigating mechanisms in crop plants for their translation in higher productivity. Multi-omics approaches comprising genomics, transcriptomics, proteomics, metabolomics and phenomics integrate studies on the interaction of plants with microbes and their external environment and generate multi-layered information that can answer what is happening in real-time within the cells. Integration, analysis and decipherization of the big-data can lead to a massive outcome that has significant chance for implementation in the fields. This review summarizes abiotic stresses responses in plants in-terms of biochemical and molecular mechanisms followed by the microbe-mediated stress mitigation phenomenon. We describe the role of multi-omics approaches in generating multi-pronged information to provide a better understanding of plant-microbe interactions that modulate cellular mechanisms in plants under extreme external conditions and help to optimize abiotic stresses. Vigilant amalgamation of these high-throughput approaches supports a higher level of knowledge generation about root-level mechanisms involved in the alleviation of abiotic stresses in organisms.

Impact of Interactive e-Learning Modules on Appropriateness of Imaging Referrals: A Multicenter, Randomized, Crossover Study.

PubMed

Velan, Gary M; Goergen, Stacy K; Grimm, Jane; Shulruf, Boaz

2015-11-01

Health care expenditure on diagnostic imaging investigations is increasing, and many tests are ordered inappropriately. Validated clinical decision rules (CDRs) for certain conditions are available to aid in assessing the need for imaging. However, awareness and utilization of CDRs are lacking. This study compared the efficacy and perceived impact of interactive e-learning modules versus static versions of CDRs, for learning about appropriate imaging referrals. A multicenter, randomized, crossover trial was performed; participants were volunteer medical students and recent graduates. In week 1, group 1 received an e-learning module on appropriate imaging referrals for pulmonary embolism; group 2 received PDF versions of relevant CDRs, and an online quiz with feedback. In week 2, the groups crossed over, focusing on imaging referrals for cervical spine trauma in adults. Online assessments were administered to both groups at the end of each week, and participants completed an online questionnaire at the end of the trial. Group 1 (e-learning module) performed significantly better on the pulmonary embolism knowledge assessment. After the crossover, participants in group 2 (e-learning module) were significantly more likely to improve their scores in the assessment of cervical spine trauma knowledge. Both groups gave positive evaluations of the e-learning modules. Interactive e-learning was significantly more effective for learning in this cohort, compared with static CDRs. We believe that the authentic clinical scenarios, feedback, and integration provided by the e-learning modules contributed to their impact. This study has implications for implementation of e-learning tools to facilitate appropriate referrals for imaging investigations in clinical practice. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.

PubMed

Lautz, Jonathan D; Brown, Emily A; VanSchoiack, Alison A Williams; Smith, Stephen E P

2018-05-27

Cells utilize dynamic, network level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co-immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co-association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co-immunoprecipitation to define the activity dependent dynamics of an 18-member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity dependent changes in two known protein-protein interactions (Homer1-mGluR5 and PSD-95-SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP-containing complexes followed by increased associations among glutamate receptors and PSD-95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co-associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of preexisting multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Integrated all-optical infrared switchable plasmonic quantum cascade laser.

PubMed

Kohoutek, John; Bonakdar, Alireza; Gelfand, Ryan; Dey, Dibyendu; Nia, Iman Hassani; Fathipour, Vala; Memis, Omer Gokalp; Mohseni, Hooman

2012-05-09

We report a type of infrared switchable plasmonic quantum cascade laser, in which far field light in the midwave infrared (MWIR, 6.1 μm) is modulated by a near field interaction of light in the telecommunications wavelength (1.55 μm). To achieve this all-optical switch, we used cross-polarized bowtie antennas and a centrally located germanium nanoslab. The bowtie antenna squeezes the short wavelength light into the gap region, where the germanium is placed. The perturbation of refractive index of the germanium due to the free carrier absorption produced by short wavelength light changes the optical response of the antenna and the entire laser intensity at 6.1 μm significantly. This device shows a viable method to modulate the far field of a laser through a near field interaction.

A physico-genetic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN)

NASA Astrophysics Data System (ADS)

Hernández-Hernández, Valeria; Barrio, Rafael A.; Benítez, Mariana; Nakayama, Naomi; Romero-Arias, José Roberto; Villarreal, Carlos

2018-05-01

Intracellular polarisation of auxin efflux carriers is crucial for understanding how auxin gradients form in plants. The polarisation dynamics of auxin efflux carriers PIN-FORMED (PIN) depends on both biomechanical forces as well as chemical, molecular and genetic factors. Biomechanical forces have shown to affect the localisation of PIN transporters to the plasma membrane. We propose a physico-genetic module of PIN polarisation that integrates biomechanical, molecular, and cellular processes as well as their non-linear interactions. The module was implemented as a discrete Boolean model and then approximated to a continuous dynamic system, in order to explore the relative contribution of the factors mediating PIN polarisation at the scale of single cell. Our models recovered qualitative behaviours that have been experimentally observed and enable us to predict that, in the context of PIN polarisation, the effects of the mechanical forces can predominate over the activity of molecular factors such as the GTPase ROP6 and the ROP-INTERACTIVE CRIB MOTIF-CONTAINING PROTEIN RIC1.

Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo.

PubMed

Jeronimo, Célia; Langelier, Marie-France; Bataille, Alain R; Pascal, John M; Pugh, B Franklin; Robert, François

2016-11-03

Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM. Interestingly, our data show that CKM regulates Mediator-UAS interaction rather than Mediator-promoter association. In addition, although Tail is required for Mediator recruitment to UAS, Tailless Mediator nevertheless interacts with core promoters. Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles. Copyright © 2016 Elsevier Inc. All rights reserved.

Scale interaction and arrangement in a turbulent boundary layer perturbed by a wall-mounted cylindrical element

NASA Astrophysics Data System (ADS)

Tang, Zhanqi; Jiang, Nan

2018-05-01

This study reports the modifications of scale interaction and arrangement in a turbulent boundary layer perturbed by a wall-mounted circular cylinder. Hot-wire measurements were executed at multiple streamwise and wall-normal wise locations downstream of the cylindrical element. The streamwise fluctuating signals were decomposed into large-, small-, and dissipative-scale signatures by corresponding cutoff filters. The scale interaction under the cylindrical perturbation was elaborated by comparing the small- and dissipative-scale amplitude/frequency modulation effects downstream of the cylinder element with the results observed in the unperturbed case. It was obtained that the large-scale fluctuations perform a stronger amplitude modulation on both the small and dissipative scales in the near-wall region. At the wall-normal positions of the cylinder height, the small-scale amplitude modulation coefficients are redistributed by the cylinder wake. The similar observation was noted in small-scale frequency modulation; however, the dissipative-scale frequency modulation seems to be independent of the cylindrical perturbation. The phase-relationship observation indicated that the cylindrical perturbation shortens the time shifts between both the small- and dissipative-scale variations (amplitude and frequency) and large-scale fluctuations. Then, the integral time scale dependence of the phase-relationship between the small/dissipative scales and large scales was also discussed. Furthermore, the discrepancy of small- and dissipative-scale time shifts relative to the large-scale motions was examined, which indicates that the small-scale amplitude/frequency leads the dissipative scales.

The impact of blended learning on student performance in a cardiovascular pharmacotherapy course.

PubMed

McLaughlin, Jacqueline E; Gharkholonarehe, Nastaran; Khanova, Julia; Deyo, Zach M; Rodgers, Jo E

2015-03-25

To examine student engagement with, perception of, and performance resulting from blended learning for venous thromboembolism in a required cardiovascular pharmacotherapy course for second-year students. In 2013, key foundational content was packaged into an interactive online module for students to access prior to coming to class; class time was dedicated to active-learning exercises. Students who accessed all online module segments participated in more in class clicker questions (p=0.043) and performed better on the examination (p=0.023). There was no difference in clicker participation or examination performance based on time of module access (prior to or after class). The majority of participants agreed or strongly agreed that foundational content learned prior to class, applied activities during class, and content-related questions in the online module greatly enhanced learning. This study highlights the importance of integrating online modules with classroom learning and the role of blended learning in improving academic performance.

Prior knowledge guided active modules identification: an integrated multi-objective approach.

PubMed

Chen, Weiqi; Liu, Jing; He, Shan

2017-03-14

Active module, defined as an area in biological network that shows striking changes in molecular activity or phenotypic signatures, is important to reveal dynamic and process-specific information that is correlated with cellular or disease states. A prior information guided active module identification approach is proposed to detect modules that are both active and enriched by prior knowledge. We formulate the active module identification problem as a multi-objective optimisation problem, which consists two conflicting objective functions of maximising the coverage of known biological pathways and the activity of the active module simultaneously. Network is constructed from protein-protein interaction database. A beta-uniform-mixture model is used to estimate the distribution of p-values and generate scores for activity measurement from microarray data. A multi-objective evolutionary algorithm is used to search for Pareto optimal solutions. We also incorporate a novel constraints based on algebraic connectivity to ensure the connectedness of the identified active modules. Application of proposed algorithm on a small yeast molecular network shows that it can identify modules with high activities and with more cross-talk nodes between related functional groups. The Pareto solutions generated by the algorithm provides solutions with different trade-off between prior knowledge and novel information from data. The approach is then applied on microarray data from diclofenac-treated yeast cells to build network and identify modules to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Gene ontology analysis is applied to the identified modules for biological interpretation. Integrating knowledge of functional groups into the identification of active module is an effective method and provides a flexible control of balance between pure data-driven method and prior information guidance.

FIBER AND INTEGRATED OPTICS: Magnetooptic interaction in fiber waveguides

NASA Astrophysics Data System (ADS)

Antonov, S. N.; Bulyuk, A. N.; Gulyaev, Yurii V.

1989-11-01

Theoretical and experimental studies were made of the effects of a distributed magnetooptic interaction in fiber waveguides. Analytic solutions were obtained for relating light modulation at the exit of a waveguide to the parameters of its winding in the form of a coil and to an external magnetic field under conditions ensuring the exact spatial phase matching. It was confirmed experimentally that the interaction length of the order of several tens of meters was quite acceptable and could ensure a sensitivity of at least 10 - 4 Oe in the case of a quartz fiber waveguide.

Morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (Macaca fascicularis).

PubMed

Conaway, Mark A; Schroeder, Lauren; von Cramon-Taubadel, Noreen

2018-03-22

Integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. Here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. The 3D morphometric data collected for eight limb and girdle bones for 60 macaques were collated into anatomical, developmental, and functional modules. A resampling technique was used to create random samples of integration values for each module for statistical comparison. Our results found that not all a priori defined modules were more strongly integrated than random samples of postcranial traits and that specific types of modules did not present consistent patterns of integration. Rather, girdle and joint modules were consistently less integrated than limb modules, and forelimb elements were less integrated than hindlimbs. The results suggest that morphometrically complex modules tend to be less integrated than simple limb bones, irrespective of the number of available traits. However, differences in integration of the fore- and hindlimb more likely reflects the multitude of locomotory, feeding, and social functions involved. It remains to be tested whether patterns of integration identified here are primate universals, and to what extent they vary depending on phylogenetic or functional factors. © 2018 Wiley Periodicals, Inc.

Development of an e-Learning Research Module Using Multimedia Instruction Approach.

PubMed

Kowitlawakul, Yanika; Chan, Moon Fai; Tan, Sharon Swee Lin; Soong, Alan Swee Kit; Chan, Sally Wai Chi

2017-03-01

Students nowadays feel more comfortable with new technologies, which increase their motivation and, as a result, improve their academic performance. In the last two decades, the use of information communication technology has been increasing in many disciplines in higher education. Online learning or e-learning has been used and integrated into the curriculum around the world. A team of nursing faculty and educational technology specialists have developed an e-learning research module and integrate it into the nursing curriculum. The aim was to assist master of nursing and postgraduate nursing students in developing their research knowledge before and throughout their enrollment in the research course. This e-learning module includes interactive multimedia such as audiovisual presentation, graphical theme, animation, case-based learning, and pretest and posttest for each topic area. The module focuses on three main topic areas: (1) basic research principles (for review), (2) quantitative method, and (3) qualitative method. The e-learning module is an innovative use of the information and communication technology to enhance student engagement and learning outcomes in a local context. This article discusses the development journey, piloting process, including the variety of evaluation perspectives, and the ways in which the results influenced the e-learning resource before its wider distribution.

The Integrated Safety-Critical Advanced Avionics Communication and Control (ISAACC) System Concept: Infrastructure for ISHM

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; Briscoe, Jeri M.

2005-01-01

Integrated System Health Management (ISHM) architectures for spacecraft will include hard real-time, critical subsystems and soft real-time monitoring subsystems. Interaction between these subsystems will be necessary and an architecture supporting multiple criticality levels will be required. Demonstration hardware for the Integrated Safety-Critical Advanced Avionics Communication & Control (ISAACC) system has been developed at NASA Marshall Space Flight Center. It is a modular system using a commercially available time-triggered protocol, ?Tp/C, that supports hard real-time distributed control systems independent of the data transmission medium. The protocol is implemented in hardware and provides guaranteed low-latency messaging with inherent fault-tolerance and fault-containment. Interoperability between modules and systems of modules using the TTP/C is guaranteed through definition of messages and the precise message schedule implemented by the master-less Time Division Multiple Access (TDMA) communications protocol. "Plug-and-play" capability for sensors and actuators provides automatically configurable modules supporting sensor recalibration and control algorithm re-tuning without software modification. Modular components of controlled physical system(s) critical to control algorithm tuning, such as pumps or valve components in an engine, can be replaced or upgraded as "plug and play" components without modification to the ISAACC module hardware or software. ISAACC modules can communicate with other vehicle subsystems through time-triggered protocols or other communications protocols implemented over Ethernet, MIL-STD- 1553 and RS-485/422. Other communication bus physical layers and protocols can be included as required. In this way, the ISAACC modules can be part of a system-of-systems in a vehicle with multi-tier subsystems of varying criticality. The goal of the ISAACC architecture development is control and monitoring of safety critical systems of a manned spacecraft. These systems include spacecraft navigation and attitude control, propulsion, automated docking, vehicle health management and life support. ISAACC can integrate local critical subsystem health management with subsystems performing long term health monitoring. The ISAACC system and its relationship to ISHM will be presented.

Chalcogenide glass-on-graphene photonics

NASA Astrophysics Data System (ADS)

Lin, Hongtao; Song, Yi; Huang, Yizhong; Kita, Derek; Deckoff-Jones, Skylar; Wang, Kaiqi; Li, Lan; Li, Junying; Zheng, Hanyu; Luo, Zhengqian; Wang, Haozhe; Novak, Spencer; Yadav, Anupama; Huang, Chung-Che; Shiue, Ren-Jye; Englund, Dirk; Gu, Tian; Hewak, Daniel; Richardson, Kathleen; Kong, Jing; Hu, Juejun

2017-12-01

Two-dimensional (2D) materials are of tremendous interest to integrated photonics, given their singular optical characteristics spanning light emission, modulation, saturable absorption and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. Here, we present a new route for 2D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material that can be directly deposited and patterned on a wide variety of 2D materials and can simultaneously function as the light-guiding medium, a gate dielectric and a passivation layer for 2D materials. Besides achieving improved fabrication yield and throughput compared with the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared waveguide-integrated photodetectors and modulators.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high- speed network capabilities. The BioSIGHT project at IMSC is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches towards the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross-disciplinary in nature and requires expertise from many areas including Biology, Computer Science, Electrical Engineering, Education, and the Cognitive Sciences. The BioSIGHT team includes a scientific illustrator, educational software designer, computer programmers as well as IMSC graduate and undergraduate students. Our collaborators include TERC, a research and education organization with extensive k-12 math and science curricula development from Cambridge, MA.; SRI International of Menlo Park, CA.; teachers and students from local area high schools (Newbury Park High School, USC's Family of Five schools, Chadwick School, and Pasadena Polytechnic High School).

Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response.

PubMed

Barrionuevo, Pablo A; Cao, Dingcai

2016-09-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.

MONGKIE: an integrated tool for network analysis and visualization for multi-omics data.

PubMed

Jang, Yeongjun; Yu, Namhee; Seo, Jihae; Kim, Sun; Lee, Sanghyuk

2016-03-18

Network-based integrative analysis is a powerful technique for extracting biological insights from multilayered omics data such as somatic mutations, copy number variations, and gene expression data. However, integrated analysis of multi-omics data is quite complicated and can hardly be done in an automated way. Thus, a powerful interactive visual mining tool supporting diverse analysis algorithms for identification of driver genes and regulatory modules is much needed. Here, we present a software platform that integrates network visualization with omics data analysis tools seamlessly. The visualization unit supports various options for displaying multi-omics data as well as unique network models for describing sophisticated biological networks such as complex biomolecular reactions. In addition, we implemented diverse in-house algorithms for network analysis including network clustering and over-representation analysis. Novel functions include facile definition and optimized visualization of subgroups, comparison of a series of data sets in an identical network by data-to-visual mapping and subsequent overlaying function, and management of custom interaction networks. Utility of MONGKIE for network-based visual data mining of multi-omics data was demonstrated by analysis of the TCGA glioblastoma data. MONGKIE was developed in Java based on the NetBeans plugin architecture, thus being OS-independent with intrinsic support of module extension by third-party developers. We believe that MONGKIE would be a valuable addition to network analysis software by supporting many unique features and visualization options, especially for analysing multi-omics data sets in cancer and other diseases. .

Network-Assisted Investigation of Combined Causal Signals from Genome-Wide Association Studies in Schizophrenia

PubMed Central

Jia, Peilin; Wang, Lily; Fanous, Ayman H.; Pato, Carlos N.; Edwards, Todd L.; Zhao, Zhongming

2012-01-01

With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each single GWAS dataset and then implemented a discovery-evaluation strategy to identify module genes with consistent association signals. We validated the module genes in an independent dataset, and also examined them through meta-analysis of the related SNPs using multiple GWAS datasets. As a result, we identified 205 module genes with a joint effect significantly associated with schizophrenia; these module genes included a number of well-studied candidate genes such as DISC1, GNA12, GNA13, GNAI1, GPR17, and GRIN2B. Further functional analysis suggested these genes are involved in neuronal related processes. Additionally, meta-analysis found that 18 SNPs in 9 module genes had P meta<1×10−4, including the gene HLA-DQA1 located in the MHC region on chromosome 6, which was reported in previous studies using the largest cohort of schizophrenia patients to date. These results demonstrated our bi-directional network-based strategy is efficient for identifying disease-associated genes with modest signals in GWAS datasets. This approach can be applied to any other complex diseases/traits where multiple GWAS datasets are available. PMID:22792057

Integrating cues of social interest and voice pitch in men's preferences for women's voices.

PubMed

Jones, Benedict C; Feinberg, David R; Debruine, Lisa M; Little, Anthony C; Vukovic, Jovana

2008-04-23

Most previous studies of vocal attractiveness have focused on preferences for physical characteristics of voices such as pitch. Here we examine the content of vocalizations in interaction with such physical traits, finding that vocal cues of social interest modulate the strength of men's preferences for raised pitch in women's voices. Men showed stronger preferences for raised pitch when judging the voices of women who appeared interested in the listener than when judging the voices of women who appeared relatively disinterested in the listener. These findings show that voice preferences are not determined solely by physical properties of voices and that men integrate information about voice pitch and the degree of social interest expressed by women when forming voice preferences. Women's preferences for raised pitch in women's voices were not modulated by cues of social interest, suggesting that the integration of cues of social interest and voice pitch when men judge the attractiveness of women's voices may reflect adaptations that promote efficient allocation of men's mating effort.

Systems and methods for selective detection and imaging in coherent Raman microscopy by spectral excitation shaping

DOEpatents

Xie, Xiaoliang Sunney; Freudiger, Christian; Min, Wei

2016-03-15

A microscopy imaging system is disclosed that includes a light source system, a spectral shaper, a modulator system, an optics system, an optical detector and a processor. The light source system is for providing a first train of pulses and a second train of pulses. The spectral shaper is for spectrally modifying an optical property of at least some frequency components of the broadband range of frequency components such that the broadband range of frequency components is shaped producing a shaped first train of pulses to specifically probe a spectral feature of interest from a sample, and to reduce information from features that are not of interest from the sample. The modulator system is for modulating a property of at least one of the shaped first train of pulses and the second train of pulses at a modulation frequency. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of a train of pulses of interest transmitted or reflected through the common focal volume. The processor is for detecting a modulation at the modulation frequency of the integrated intensity of substantially all of the optical frequency components of the train of pulses of interest due to the non-linear interaction of the shaped first train of pulses with the second train of pulses as modulated in the common focal volume, and for providing an output signal for a pixel of an image for the microscopy imaging system.

D3GB: An Interactive Genome Browser for R, Python, and WordPress.

PubMed

Barrios, David; Prieto, Carlos

2017-05-01

Genome browsers are useful not only for showing final results but also for improving analysis protocols, testing data quality, and generating result drafts. Its integration in analysis pipelines allows the optimization of parameters, which leads to better results. New developments that facilitate the creation and utilization of genome browsers could contribute to improving analysis results and supporting the quick visualization of genomic data. D3 Genome Browser is an interactive genome browser that can be easily integrated in analysis protocols and shared on the Web. It is distributed as an R package, a Python module, and a WordPress plugin to facilitate its integration in pipelines and the utilization of platform capabilities. It is compatible with popular data formats such as GenBank, GFF, BED, FASTA, and VCF, and enables the exploration of genomic data with a Web browser.

Dual Coordination of Post Translational Modifications in Human Protein Networks

PubMed Central

Woodsmith, Jonathan; Kamburov, Atanas; Stelzl, Ulrich

2013-01-01

Post-translational modifications (PTMs) regulate protein activity, stability and interaction profiles and are critical for cellular functioning. Further regulation is gained through PTM interplay whereby modifications modulate the occurrence of other PTMs or act in combination. Integration of global acetylation, ubiquitination and tyrosine or serine/threonine phosphorylation datasets with protein interaction data identified hundreds of protein complexes that selectively accumulate each PTM, indicating coordinated targeting of specific molecular functions. A second layer of PTM coordination exists in these complexes, mediated by PTM integration (PTMi) spots. PTMi spots represent very dense modification patterns in disordered protein regions and showed an equally high mutation rate as functional protein domains in cancer, inferring equivocal importance for cellular functioning. Systematic PTMi spot identification highlighted more than 300 candidate proteins for combinatorial PTM regulation. This study reveals two global PTM coordination mechanisms and emphasizes dataset integration as requisite in proteomic PTM studies to better predict modification impact on cellular signaling. PMID:23505349

New Educational Modules Using a Cyber-Distribution System Testbed

DOE PAGES

Xie, Jing; Bedoya, Juan Carlos; Liu, Chen-Ching; ...

2018-03-30

At Washington State University (WSU), a modern cyber-physical system testbed has been implemented based on an industry grade distribution management system (DMS) that is integrated with remote terminal units (RTUs), smart meters, and a solar photovoltaic (PV). In addition, the real model from the Avista Utilities distribution system in Pullman, WA, is modeled in DMS. The proposed testbed environment allows students and instructors to utilize these facilities for innovations in learning and teaching. For power engineering education, this testbed helps students understand the interaction between a cyber system and a physical distribution system through industrial level visualization. The testbed providesmore » a distribution system monitoring and control environment for students. Compared with a simulation based approach, the testbed brings the students' learning environment a step closer to the real world. The educational modules allow students to learn the concepts of a cyber-physical system and an electricity market through an integrated testbed. Furthermore, the testbed provides a platform in the study mode for students to practice working on a real distribution system model. Here, this paper describes the new educational modules based on the testbed environment. Three modules are described together with the underlying educational principles and associated projects.« less

New Educational Modules Using a Cyber-Distribution System Testbed

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

Xie, Jing; Bedoya, Juan Carlos; Liu, Chen-Ching

At Washington State University (WSU), a modern cyber-physical system testbed has been implemented based on an industry grade distribution management system (DMS) that is integrated with remote terminal units (RTUs), smart meters, and a solar photovoltaic (PV). In addition, the real model from the Avista Utilities distribution system in Pullman, WA, is modeled in DMS. The proposed testbed environment allows students and instructors to utilize these facilities for innovations in learning and teaching. For power engineering education, this testbed helps students understand the interaction between a cyber system and a physical distribution system through industrial level visualization. The testbed providesmore » a distribution system monitoring and control environment for students. Compared with a simulation based approach, the testbed brings the students' learning environment a step closer to the real world. The educational modules allow students to learn the concepts of a cyber-physical system and an electricity market through an integrated testbed. Furthermore, the testbed provides a platform in the study mode for students to practice working on a real distribution system model. Here, this paper describes the new educational modules based on the testbed environment. Three modules are described together with the underlying educational principles and associated projects.« less

Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

PubMed Central

Chowdhury, Debashish

2013-01-01

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

Design and implementation of a 3D ocean virtual reality and visualization engine

NASA Astrophysics Data System (ADS)

Chen, Ge; Li, Bo; Tian, Fenglin; Ji, Pengbo; Li, Wenqing

2012-12-01

In this study, a 3D virtual reality and visualization engine for rendering the ocean, named VV-Ocean, is designed for marine applications. The design goals of VV-Ocean aim at high fidelity simulation of ocean environment, visualization of massive and multidimensional marine data, and imitation of marine lives. VV-Ocean is composed of five modules, i.e. memory management module, resources management module, scene management module, rendering process management module and interaction management module. There are three core functions in VV-Ocean: reconstructing vivid virtual ocean scenes, visualizing real data dynamically in real time, imitating and simulating marine lives intuitively. Based on VV-Ocean, we establish a sea-land integration platform which can reproduce drifting and diffusion processes of oil spilling from sea bottom to surface. Environment factors such as ocean current and wind field have been considered in this simulation. On this platform oil spilling process can be abstracted as movements of abundant oil particles. The result shows that oil particles blend with water well and the platform meets the requirement for real-time and interactive rendering. VV-Ocean can be widely used in ocean applications such as demonstrating marine operations, facilitating maritime communications, developing ocean games, reducing marine hazards, forecasting the weather over oceans, serving marine tourism, and so on. Finally, further technological improvements of VV-Ocean are discussed.

Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System.

PubMed

Chojnacka, Magdalena; Gornicka, Agnieszka; Oeljeklaus, Silke; Warscheid, Bettina; Chacinska, Agnieszka

2015-06-12

The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity. This interaction does not involve Sco1, a partner of Cox17 in transferring copper ions to cytochrome c oxidase. However, the Cox17-MICOS interaction is regulated by copper ions. We propose that Cox17 is a newly identified factor involved in maintaining the architecture of the MICOS complex. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Evanescent-field-modulated two-qubit entanglement in an emitters-plasmon coupled system.

PubMed

Zhang, Fan; Ren, Juanjuan; Duan, Xueke; Zhao, Chen; Gong, Qihuang; Gu, Ying

2018-06-13

Scalable integrated quantum information networks calls for controllable entanglement modulation at subwavelength scale. To reduce laser disturbance among adjacent nanostructures, here we theoretically demonstrate two-qubit entanglement modulated by an evanescent field of a dielectric nanowire in an emitter-AgNP coupled system. This coupled system is considered as a nano-cavity system embedded in an evanescent vacuum. Through varying the amplitude of evanescent field, the concurrence of steady-state entanglement can be modified from 0 to 0.75. Because the interaction between emitters and the nanowire is much weaker than that inside the coupled system, the range of modulation for two-qubit entanglement is insensitive to their distance. The evanescent field controlled entangled state engineering provides the possibility to avoid optical crosstalk for on-chip steady-state entanglement. © 2018 IOP Publishing Ltd.

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy.

PubMed

de Souza, Heitor S P; Fiocchi, Claudio; Iliopoulos, Dimitrios

2017-12-01

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant -omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual -omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple -omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

Interprofessional communication training: benefits to practicing pharmacists.

PubMed

Luetsch, Karen; Rowett, Debra

2015-10-01

Interprofessional communication skills are important for pharmacists to build collaborative relationships with other health professionals, integrate into healthcare teams, maximise their effectiveness in patient care in addressing complex care needs and meet the demands of health care reforms. This qualitative study explores clinical pharmacists' experiences and reflections after completing a learning and practice module which introduced them to a framework for successful interprofessional communication. The postgraduate clinical pharmacy program at The University of Queensland and the clinical pharmacy practice environments of forty-eight hospital and seven community based pharmacists. A learning and practice module outlining a framework for successful interprofessional communication was designed and integrated into a postgraduate clinical pharmacy program. Enrolled pharmacists applied newly learnt communication skills in pro-actively initiated, clinical discussions with a health professional in their practice environment. They provided written reflections on their experiences which were analysed using thematic analysis. Pharmacists' perceptions of the impact of applying the communication framework during their interaction with a health professional in their practice setting. Themes which emerged from reflections described pharmacists' confidence and capabilities to successfully conduct a clinical discussion with a health professional after initial apprehension and nervousness about the scheduled interaction. The application of the communication framework enhanced their perception of their professional identity, credibility and ability to build a collaborative working relationship with other health professionals. Pharmacists perceived that a learning and practice module for successful interprofessional practice integrated into a postgraduate clinical pharmacy program enhanced their interprofessional communication skills. The development of pro-active, interprofessional communication skills has the potential to increase interprofessional collaboration and pharmacists' personal role satisfaction. Pharmacists also observed it added value to their professional contribution in health care teams when addressing the demands of increasingly complex health care needs and reforms.

Development of a frequency-modulated ultrasonic sensor inspired by bat echolocation

NASA Astrophysics Data System (ADS)

Kepa, Krzysztof; Abaid, Nicole

2015-03-01

Bats have evolved to sense using ultrasonic signals with a variety of different frequency signatures which interact with their environment. Among these signals, those with time-varying frequencies may enable the animals to gather more complex information for obstacle avoidance and target tracking. Taking inspiration from this system, we present the development of a sonar sensor capable of generating frequency-modulated ultrasonic signals. The device is based on a miniature mobile computer, with on board data capture and processing capabilities, which is designed for eventual autonomous operation in a robotic swarm. The hardware and software components of the sensor are detailed, as well their integration. Preliminary results for target detection using both frequency-modulated and constant frequency signals are discussed.

The Modular Organization of Protein Interactions in Escherichia coli

PubMed Central

Peregrín-Alvarez, José M.; Xiong, Xuejian; Su, Chong; Parkinson, John

2009-01-01

Escherichia coli serves as an excellent model for the study of fundamental cellular processes such as metabolism, signalling and gene expression. Understanding the function and organization of proteins within these processes is an important step towards a ‘systems’ view of E. coli. Integrating experimental and computational interaction data, we present a reliable network of 3,989 functional interactions between 1,941 E. coli proteins (∼45% of its proteome). These were combined with a recently generated set of 3,888 high-quality physical interactions between 918 proteins and clustered to reveal 316 discrete modules. In addition to known protein complexes (e.g., RNA and DNA polymerases), we identified modules that represent biochemical pathways (e.g., nitrate regulation and cell wall biosynthesis) as well as batteries of functionally and evolutionarily related processes. To aid the interpretation of modular relationships, several case examples are presented, including both well characterized and novel biochemical systems. Together these data provide a global view of the modular organization of the E. coli proteome and yield unique insights into structural and evolutionary relationships in bacterial networks. PMID:19798435

3D Slicer as a tool for interactive brain tumor segmentation.

PubMed

Kikinis, Ron; Pieper, Steve

2011-01-01

User interaction is required for reliable segmentation of brain tumors in clinical practice and in clinical research. By incorporating current research tools, 3D Slicer provides a set of interactive, easy to use tools that can be efficiently used for this purpose. One of the modules of 3D Slicer is an interactive editor tool, which contains a variety of interactive segmentation effects. Use of these effects for fast and reproducible segmentation of a single glioblastoma from magnetic resonance imaging data is demonstrated. The innovation in this work lies not in the algorithm, but in the accessibility of the algorithm because of its integration into a software platform that is practical for research in a clinical setting.

SIRE: A Simple Interactive Rule Editor for NICBES

NASA Technical Reports Server (NTRS)

Bykat, Alex

1988-01-01

To support evolution of domain expertise, and its representation in an expert system knowledge base, a user-friendly rule base editor is mandatory. The Nickel Cadmium Battery Expert System (NICBES), a prototype of an expert system for the Hubble Space Telescope power storage management system, does not provide such an editor. In the following, a description of a Simple Interactive Rule Base Editor (SIRE) for NICBES is described. The SIRE provides a consistent internal representation of the NICBES knowledge base. It supports knowledge presentation and provides a user-friendly and code language independent medium for rule addition and modification. The SIRE is integrated with NICBES via an interface module. This module provides translation of the internal representation to Prolog-type rules (Horn clauses), latter rule assertion, and a simple mechanism for rule selection for its Prolog inference engine.

Cellular and molecular specificity of pituitary gland physiology.

PubMed

Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

2012-01-01

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

Integrating Ultrasound Teaching into Preclinical Problem-based Learning

PubMed Central

Tshibwabwa, Eli Tumba; Cannon, Jenifer; Rice, James; Kawooya, Michael G; Sanii, Reza; Mallin, Robert

2016-01-01

Objectives: The aim is to provide students in the preclinical with ultrasound image interpretation skills. Research question: Are students in smaller groups with access to a combination of lectures and hands-on patient contact most likely to have better ultrasound image interpretation skills, than students in larger groups with only interactive didactic lectures? Methodology: First-year students at the preclinical Program of the College of Medicine, participated in two 2-h introductory interactive ultrasound sessions. The study comprised two cohorts: 2012/2013 students, who were offered large group teaching (LGT) sessions (control group), and 2013/2014 students, who received the intervention in small group learning problem-based learning (PBL) sessions (experimental group). The overall learning objectives were identical for both groups. The success of the module was evaluated using pre- and post-tests as well as students’ feedback. Results: The students in the experimental group showed significantly higher scores in interpretations of images than those in the control group. The experimental group showed achievement of learning outcomes along with higher levels of satisfaction with the module compared to the latter. Conclusion: Posttest knowledge of the basics of ultrasound improved significantly over the pretest in the experimental group. In addition, students’ overall satisfaction of the ultrasound module was shown to be higher for the PBL compared to the LGT groups. Small groups in an interactive and PBL setting along with opportunities for hands-on practice and simultaneous visualization of findings on a high definition screen should enhance preclinical student learning of the basics of ultrasound. Despite the potential of ultrasound as a clinical, teaching and learning tool for students in the preclinical years, standardized recommendations have yet to be created regarding its integration into the curricula within academic institutions and clinical medicine. The interactive and PBL is here to stay at the college of medicine. Further research would be carried out to see if this trend persists in the upcoming vertical system-based curriculum of the college of medicine. PMID:27833780

Communicative Interactions in Everyday and College-Assessed Digital Literacy Practices: Transcribing and Analysing Multimodal Texts

ERIC Educational Resources Information Center

Creer, Adele

2017-01-01

This paper explores integrating a range of digital media into classroom practice to establish the effectiveness of the media and its encompassing modes as a pedagogical tool with a focus on assessment. Directing attention on a communication skills module, research indicated that bringing a range of digital media into the classroom motivated and…

A Blended-Learning Pedagogical Model for Teaching and Learning EFL Successfully through an Online Interactive Multimedia Environment

ERIC Educational Resources Information Center

Banados, Emerita

2006-01-01

Faced with the need to teach English to a large number of students, the "Universidad de Concepcion," Chile, has created an innovative Communicative English Program using ICT, which is made up of four modules covered in four academic terms. The English program aims to develop integrated linguistic skills with a focus on learning for…

PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3.

PubMed

Remy, Ingrid; Montmarquette, Annie; Michnick, Stephen W

2004-04-01

Transforming growth factor beta (TGF-beta) has a major role in cell proliferation, differentiation and apoptosis in many cell types. Integration of the TGF-beta pathway with other signalling cascades that control the same cellular processes may modulate TGF-beta responses. Here we report the discovery of a new functional link between TGF-beta and growth factor signalling pathways, mediated by a physical interaction between the serine-threonine kinase PKB (protein kinase B)/Akt and the transcriptional activator Smad3. Formation of the complex is induced by insulin, but inhibited by TGF-beta stimulation, placing PKB-Smad3 at a point of convergence between these two pathways. PKB inhibits Smad3 by preventing its phosphorylation, binding to Smad4 and nuclear translocation. In contrast, Smad3 does not inhibit PKB. Inhibition of Smad3 by PKB occurs through a kinase-activity-independent mechanism, resulting in a decrease in Smad3-mediated transcription and protection of cells against TGF-beta-induced apoptosis. Consistently, knockdown of the endogenous PKB gene with small-interfering RNA (siRNA) has the opposite effect. Our results suggest a very simple mechanism for the integration of signals arising from growth-factor- and TGF-beta-mediated pathways.

HCI∧2 framework: a software framework for multimodal human-computer interaction systems.

PubMed

Shen, Jie; Pantic, Maja

2013-12-01

This paper presents a novel software framework for the development and research in the area of multimodal human-computer interface (MHCI) systems. The proposed software framework, which is called the HCI∧2 Framework, is built upon publish/subscribe (P/S) architecture. It implements a shared-memory-based data transport protocol for message delivery and a TCP-based system management protocol. The latter ensures that the integrity of system structure is maintained at runtime. With the inclusion of bridging modules, the HCI∧2 Framework is interoperable with other software frameworks including Psyclone and ActiveMQ. In addition to the core communication middleware, we also present the integrated development environment (IDE) of the HCI∧2 Framework. It provides a complete graphical environment to support every step in a typical MHCI system development process, including module development, debugging, packaging, and management, as well as the whole system management and testing. The quantitative evaluation indicates that our framework outperforms other similar tools in terms of average message latency and maximum data throughput under a typical single PC scenario. To demonstrate HCI∧2 Framework's capabilities in integrating heterogeneous modules, we present several example modules working with a variety of hardware and software. We also present an example of a full system developed using the proposed HCI∧2 Framework, which is called the CamGame system and represents a computer game based on hand-held marker(s) and low-cost camera(s).

RF to millimeter wave integration and module technologies

NASA Astrophysics Data System (ADS)

Vähä-Heikkilä, T.

2015-04-01

Radio Frequency (RF) consumer applications have boosted silicon integrated circuits (IC) and corresponding technologies. More and more functions are integrated to ICs and their performance is also increasing. However, RF front-end modules with filters and switches as well as antennas still need other way of integration. This paper focuses to RF front-end module and antenna developments as well as to the integration of millimeter wave radios. VTT Technical Research Centre of Finland has developed both Low Temperature Co-fired Ceramics (LTCC) and Integrated Passive Devices (IPD) integration platforms for RF and millimeter wave integrated modules. In addition to in-house technologies, VTT is using module and component technologies from other commercial sources.

Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network

PubMed Central

Sun, Shuguo; Irvine, Kenneth D.

2016-01-01

The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated, and to define their respective contributions in vivo. PMID:27268910

Pediatric trainees' engagement in the online nutrition curriculum: preliminary results.

PubMed

Lewis, Kadriye O; Frank, Graeme R; Nagel, Rollin; Turner, Teri L; Ferrell, Cynthia L; Sangvai, Shilpa G; Donthi, Rajesh; Mahan, John D

2014-09-16

The Pediatric Nutrition Series (PNS) consists of ten online, interactive modules and supplementary educational materials that have utilized web-based multimedia technologies to offer nutrition education for pediatric trainees and practicing physicians. The purpose of the study was to evaluate pediatric trainees' engagement, knowledge acquisition, and satisfaction with nutrition modules delivered online in interactive and non-interactive formats. From December 2010 through August 2011, pediatric trainees from seventy-three (73) different U.S. programs completed online nutrition modules designed to develop residents' knowledge of counseling around and management of nutritional issues in children. Data were analyzed using SPSS version 19. Both descriptive and inferential statistics were used in comparing interactive versus non-interactive modules. Pretest/posttest and module evaluations measured knowledge acquisition and satisfaction. Three hundred and twenty-two (322) pediatric trainees completed one or more of six modules for a total of four hundred and forty-two (442) accessions. All trainees who completed at least one module were included in the study. Two-way analyses of variance (ANOVA) with repeated measures (pre/posttest by interactive/non-interactive format) indicated significant knowledge gains from pretest to posttest (p < 0.002 for all six modules). Comparisons between interactive and non-interactive formats for Module 1 (N = 85 interactive, N = 95 non-interactive) and Module 5 (N = 5 interactive, N = 16 non-interactive) indicated a parallel improvement from the pretest to posttest, with the interactive format significantly higher than the non-interactive modules (p < .05). Both qualitative and quantitative data from module evaluations demonstrated that satisfaction with modules was high. However, there were lower ratings for whether learning objectives were met with Module 6 (p < 0.03) and lecturer rating (p < 0.004) compared to Module 1. Qualitative data also showed that completion of the interactive modules resulted in higher resident satisfaction. This initial assessment of the PNS modules shows that technology-mediated delivery of a nutrition curriculum in residency programs has great potential for providing rich learning environments for trainees while maintaining a high level of participant satisfaction.

An Integrated Decision Support System for Water Quality Management of Songhua River Basin

NASA Astrophysics Data System (ADS)

Zhang, Haiping; Yin, Qiuxiao; Chen, Ling

2010-11-01

In the Songhua River Basin of China, many water resource and water environment conflicts interact. A Decision Support System (DSS) for the water quality management has been established for the Basin. The System is featured by the incorporation of a numerical water quality model system into a conventional water quality management system which usually consists of geographic information system (GIS), WebGIS technology, database system and network technology. The model system is built based on DHI MIKE software comprising of a basin rainfall-runoff module, a basin pollution load evaluation module, a river hydrodynamic module and a river water quality module. The DSS provides a friendly graphical user interface that enables the rapid and transparent calculation of various water quality management scenarios, and also enables the convenient access and interpretation of the modeling results to assist the decision-making.

The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

PubMed

Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Flemington, Erik K; Zhang, Kun

2016-08-01

Ovarian carcinoma is the fifth-leading cause of cancer death among women in the United States. Major reasons for this persistent mortality include the poor understanding of the underlying biology and a lack of reliable biomarkers. Previous studies have shown that aberrantly expressed MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by post-transcriptionally regulating gene expression. However, the interference of miRNAs in tumorigenesis is quite complicated and far from being fully understood. In this work, by an integrative analysis of mRNA expression, miRNA expression and clinical data published by The Cancer Genome Atlas (TCGA), we studied the modularity and dynamicity of miRNA-mRNA interactions and the prognostic implications in high-grade serous ovarian carcinomas. With the top transcriptional correlations (Bonferroni-adjusted p-value<0.01) as inputs, we identified five miRNA-mRNA module pairs (MPs), each of which included one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs in each module varied from 3 to 7 or from 2 to 873. Among the four major negative-connection modules, three fit well with the widely accepted miRNA-mediated post-transcriptional regulation theory. These modules were enriched with the genes relevant to cell cycle and immune response. Moreover, we proposed two novel algorithms to reveal the group or sample specific dynamic regulations between these two RNA classes. The obtained miRNA-mRNA dynamic network contains 3350 interactions captured across different cancer progression stages or tumor grades. We found that those dynamic interactions tended to concentrate on a few miRNAs (e.g. miRNA-936), and were more likely present on the miRNA-mRNA pairs outside the discovered modules. In addition, we also pinpointed a robust prognostic signature consisting of 56 modular protein-coding genes, whose co-expression patterns were predictive for the survival time of ovarian cancer patients in multiple independent cohorts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Individual differences in action co-representation: not personal distress or subclinical psychotic experiences but sex composition modulates joint action performance.

PubMed

van der Weiden, Anouk; Aarts, Henk; Prikken, Merel; van Haren, Neeltje E M

2016-02-01

Successful social interaction requires the ability to integrate as well as distinguish own and others' actions. Normally, the integration and distinction of self and other are a well-balanced process, occurring without much effort or conscious attention. However, not everyone is blessed with the ability to balance self-other distinction and integration, resulting in personal distress in reaction to other people's emotions or even a loss of self [e.g., in (subclinical) psychosis]. Previous research has demonstrated that the integration and distinction of others' actions cause interference with one's own action performance (commonly assessed with a social Simon task). The present study had two goals. First, as previous studies on the social Simon effect employed relatively small samples (N < 50 per test), we aimed for a sample size that allowed us to test the robustness of the action interference effect. Second, we tested to what extent action interference reflects individual differences in traits related to self-other distinction (i.e., personal distress in reaction to other people's emotions and subclinical psychotic symptoms). Based on a questionnaire study among a large sample (N = 745), we selected a subsample (N = 130) of participants scoring low, average, or high on subclinical psychotic symptoms, or on personal distress. The selected participants performed a social Simon task. Results showed a robust social Simon effect, regardless of individual differences in personal distress or subclinical psychotic symptoms. However, exploratory analyses revealed that the sex composition of interaction pairs modulated social Simon effects. Possible explanations for these findings are discussed.

Biotic Interactions in Microbial Communities as Modulators of Biogeochemical Processes: Methanotrophy as a Model System

PubMed Central

Ho, Adrian; Angel, Roey; Veraart, Annelies J.; Daebeler, Anne; Jia, Zhongjun; Kim, Sang Yoon; Kerckhof, Frederiek-Maarten; Boon, Nico; Bodelier, Paul L. E.

2016-01-01

Microbial interaction is an integral component of microbial ecology studies, yet the role, extent, and relevance of microbial interaction in community functioning remains unclear, particularly in the context of global biogeochemical cycles. While many studies have shed light on the physico-chemical cues affecting specific processes, (micro)biotic controls and interactions potentially steering microbial communities leading to altered functioning are less known. Yet, recent accumulating evidence suggests that the concerted actions of a community can be significantly different from the combined effects of individual microorganisms, giving rise to emergent properties. Here, we exemplify the importance of microbial interaction for ecosystem processes by analysis of a reasonably well-understood microbial guild, namely, aerobic methane-oxidizing bacteria (MOB). We reviewed the literature which provided compelling evidence for the relevance of microbial interaction in modulating methane oxidation. Support for microbial associations within methane-fed communities is sought by a re-analysis of literature data derived from stable isotope probing studies of various complex environmental settings. Putative positive interactions between active MOB and other microbes were assessed by a correlation network-based analysis with datasets covering diverse environments where closely interacting members of a consortium can potentially alter the methane oxidation activity. Although, methanotrophy is used as a model system, the fundamentals of our postulations may be applicable to other microbial guilds mediating other biogeochemical processes. PMID:27602021

The Impact of Blended Learning on Student Performance in a Cardiovascular Pharmacotherapy Course

PubMed Central

McLaughlin, Jacqueline E.; Gharkholonarehe, Nastaran; Khanova, Julia; Deyo, Zach M.

2015-01-01

Objective. To examine student engagement with, perception of, and performance resulting from blended learning for venous thromboembolism in a required cardiovascular pharmacotherapy course for second-year students. Design. In 2013, key foundational content was packaged into an interactive online module for students to access prior to coming to class; class time was dedicated to active-learning exercises. Assessment. Students who accessed all online module segments participated in more in class clicker questions (p=0.043) and performed better on the examination (p=0.023). There was no difference in clicker participation or examination performance based on time of module access (prior to or after class). The majority of participants agreed or strongly agreed that foundational content learned prior to class, applied activities during class, and content-related questions in the online module greatly enhanced learning. Conclusion. This study highlights the importance of integrating online modules with classroom learning and the role of blended learning in improving academic performance. PMID:25861105

Multisensory integration and attention in autism spectrum disorder: evidence from event-related potentials.

PubMed

Magnée, Maurice J C M; de Gelder, Beatrice; van Engeland, Herman; Kemner, Chantal

2011-01-01

Successful integration of various simultaneously perceived perceptual signals is crucial for social behavior. Recent findings indicate that this multisensory integration (MSI) can be modulated by attention. Theories of Autism Spectrum Disorders (ASDs) suggest that MSI is affected in this population while it remains unclear to what extent this is related to impairments in attentional capacity. In the present study Event-related potentials (ERPs) following emotionally congruent and incongruent face-voice pairs were measured in 23 high-functioning, adult ASD individuals and 24 age- and IQ-matched controls. MSI was studied while the attention of the participants was manipulated. ERPs were measured at typical auditory and visual processing peaks, namely, P2 and N170. While controls showed MSI during divided attention and easy selective attention tasks, individuals with ASD showed MSI during easy selective attention tasks only. It was concluded that individuals with ASD are able to process multisensory emotional stimuli, but this is differently modulated by attention mechanisms in these participants, especially those associated with divided attention. This atypical interaction between attention and MSI is also relevant to treatment strategies, with training of multisensory attentional control possibly being more beneficial than conventional sensory integration therapy.

Coupling control based on Adiabatic elimination for densely integrated nano-photonics

NASA Astrophysics Data System (ADS)

Mrejen, Michael; Suchowski, Haim; Hatakeyama, Taiki; Wu, Chihhui; Feng, Liang; O'Brien, Kevin; Wang, Yuan; Zhang, Xiang

2015-03-01

The ever growing need for energy-efficient and fast communications is driving the development of highly integrated photonic circuits where controlling light at the nanoscale becomes the most critical aspect of information transfer. Here we develop a unique scheme of adiabatic elimination (AE) modulation to actively control the coupling among waveguides for densely integrated photonics. Analogous to atomic systems, AE is achieved by applying a decomposition on a three waveguide coupler, where the two outer waveguides serve as an effective two-mode system with an effective coupling of Veff = [(V*13 + V*23V*12/Δβ12) (V13-V23V12/Δβ23) ]1/2,and the middle waveguide is the equivalent to the intermediate level `dark state'. We experimentally demonstrate the first all optical AE modulation and its ability to control the coupling between the two waveguides by manipulating the mode index of the decoupled middle one. In addition, we show that the strong modes interactions allowed at the nano-scale offer a unique configuration of zero-coupling between all the waveguides, a phenomena that paves the way for ultra-high density photonic integrated circuits where small footprint is of crucial importance.

Fully-Integrated Simulation of Conjunctive Use from Field to Basin Scales: Development of a Surface Water Operations Module for MODFLOW-OWHM

NASA Astrophysics Data System (ADS)

Ferguson, I. M.; Boyce, S. E.; Hanson, R. T.; Llewellyn, D.

2014-12-01

It is well established that groundwater pumping affects surface-water availability by intercepting groundwater that would otherwise discharge to streams and/or by increasing seepage from surface-water channels. Conversely, surface-water management operations effect groundwater availability by altering the timing, location, and quantity of groundwater recharge and demand. Successful conjunctive use may require analysis with an integrated approach that accounts for the many interactions and feedbacks between surface-water and groundwater availability and their joint management. In order to improve simulation and analysis of conjunctive use, Bureau of Reclamation and USGS are collaborating to develop a surface-water operations module within MODFLOW One Water Hydrologic Flow Model (MF-OWHM), a new version of the USGS Modular Groundwater Flow Model (MODFLOW). Here we describe the development and application of the surface-water operations module. We provide an overview of the conceptual approach used to simulate surface-water operations—including surface-water storage, allocation, release, diversion, and delivery on monthly to seasonal time frames—in a fully-integrated manner. We then present results from a recent case study analysis of the Rio Grande Project, a large-scale irrigation project located in New Mexico and Texas, under varying surface-water operations criteria and climate conditions. Case study results demonstrate the importance of integrated hydrologic simulation of surface water and groundwater operations in analysis and management of conjunctive-use systems.

IAC-1.5 - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Vos, R. G.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and a database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a database, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automating data transfer among analysis programs. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation modules are supplied for building and viewing models. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files, object code, etc. The user can define groups of data and relations between them. A full data manipulation and query system operates with the database. The current interface modules comprise five groups: 1) Structural analysis - IAC contains a NASTRAN interface for standalone analysis or certain structural/control/thermal combinations. IAC provides enhanced structural capabilities for normal modes and static deformation analysis via special DMAP sequences. 2) Thermal analysis - IAC supports finite element and finite difference techniques for steady state or transient analysis. There are interfaces for the NASTRAN thermal analyzer, SINDA/SINFLO, and TRASYS II. 3) System dynamics - A DISCOS interface allows full use of this simulation program for either nonlinear time domain analysis or linear frequency domain analysis. 4) Control analysis - Interfaces for the ORACLS, SAMSAN, NBOD2, and INCA programs allow a wide range of control system analyses and synthesis techniques. 5) Graphics - The graphics packages PLOT and MOSAIC are included in IAC. PLOT generates vector displays of tabular data in the form of curves, charts, correlation tables, etc., while MOSAIC generates color raster displays of either tabular of array type data. Either DI3000 or PLOT-10 graphics software is required for full graphics capability. IAC is available by license for a period of 10 years to approved licensees. The licensed program product includes one complete set of supporting documentation. Additional copies of the documentation may be purchased separately. IAC is written in FORTRAN 77 and has been implemented on a DEC VAX series computer operating under VMS. IAC can be executed by multiple concurrent users in batch or interactive mode. The basic central memory requirement is approximately 750KB. IAC includes the executive system, graphics modules, a database, general utilities, and the interfaces to all analysis and controls programs described above. Source code is provided for the control programs ORACLS, SAMSAN, NBOD2, and DISCOS. The following programs are also available from COSMIC a

IAC-1.5 - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Vos, R. G.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and a database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a database, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automating data transfer among analysis programs. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation modules are supplied for building and viewing models. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files, object code, etc. The user can define groups of data and relations between them. A full data manipulation and query system operates with the database. The current interface modules comprise five groups: 1) Structural analysis - IAC contains a NASTRAN interface for standalone analysis or certain structural/control/thermal combinations. IAC provides enhanced structural capabilities for normal modes and static deformation analysis via special DMAP sequences. 2) Thermal analysis - IAC supports finite element and finite difference techniques for steady state or transient analysis. There are interfaces for the NASTRAN thermal analyzer, SINDA/SINFLO, and TRASYS II. 3) System dynamics - A DISCOS interface allows full use of this simulation program for either nonlinear time domain analysis or linear frequency domain analysis. 4) Control analysis - Interfaces for the ORACLS, SAMSAN, NBOD2, and INCA programs allow a wide range of control system analyses and synthesis techniques. 5) Graphics - The graphics packages PLOT and MOSAIC are included in IAC. PLOT generates vector displays of tabular data in the form of curves, charts, correlation tables, etc., while MOSAIC generates color raster displays of either tabular of array type data. Either DI3000 or PLOT-10 graphics software is required for full graphics capability. IAC is available by license for a period of 10 years to approved licensees. The licensed program product includes one complete set of supporting documentation. Additional copies of the documentation may be purchased separately. IAC is written in FORTRAN 77 and has been implemented on a DEC VAX series computer operating under VMS. IAC can be executed by multiple concurrent users in batch or interactive mode. The basic central memory requirement is approximately 750KB. IAC includes the executive system, graphics modules, a database, general utilities, and the interfaces to all analysis and controls programs described above. Source code is provided for the control programs ORACLS, SAMSAN, NBOD2, and DISCOS. The following programs are also available from COSMIC as separate packages: NASTRAN, SINDA/SINFLO, TRASYS II, DISCOS, ORACLS, SAMSAN, NBOD2, and INCA. IAC was developed in 1985.

Modelling surface water-groundwater interaction with a conceptual approach: model development and application in New Zealand

NASA Astrophysics Data System (ADS)

Yang, J.; Zammit, C.; McMillan, H. K.

2016-12-01

As in most countries worldwide, water management in lowland areas is a big concern for New Zealand due to its economic importance for water related human activities. As a result, the estimation of available water resources in these areas (e.g., for irrigation and water supply purpose) is crucial and often requires an understanding of complex hydrological processes, which are often characterized by strong interactions between surface water and groundwater (usually expressed as losing and gaining rivers). These processes are often represented and simulated using integrated physically based hydrological models. However models with physically based groundwater modules typically require large amount of non-readily available geologic and aquifer information and are computationally intensive. Instead, this paper presents a conceptual groundwater model that is fully integrated into New Zealand's national hydrological model TopNet based on TopModel concepts (Beven, 1992). Within this conceptual framework, the integrated model can simulate not only surface processes, but also groundwater processes and surface water-groundwater interaction processes (including groundwater flow, river-groundwater interaction, and groundwater interaction with external watersheds). The developed model was applied to two New Zealand catchments with different hydro-geological and climate characteristics (Pareora catchment in the Canterbury Plains and Grey catchment on the West Coast). Previous studies have documented strong interactions between the river and groundwater, based on the analysis of a large number of concurrent flow measurements and associated information along the river main stem. Application of the integrated hydrological model indicates flow simulation (compared to the original hydrological model conceptualisation) during low flow conditions are significantly improved and further insights on local river dynamics are gained. Due to its conceptual characteristics and low level of data requirement, the integrated model could be used at local and national scales to improve the simulation of hydrological processes in non-topographically driven areas (where groundwater processes are important), and to assess impact of climate change on the integrated hydrological cycle in these areas.

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease.

PubMed

Novati, Arianna; Hentrich, Thomas; Wassouf, Zinah; Weber, Jonasz J; Yu-Taeger, Libo; Déglon, Nicole; Nguyen, Huu Phuc; Schulze-Hentrich, Julia M

2018-04-11

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene which results in progressive neurodegeneration in the striatum, cortex, and eventually most brain areas. Despite being a monogenic disorder, environmental factors influence HD characteristics. Both human and mouse studies suggest that mutant HTT (mHTT) leads to gene expression changes that harbor potential to be modulated by the environment. Yet, the underlying mechanisms integrating environmental cues into the gene regulatory program have remained largely unclear. To better understand gene-environment interactions in the context of mHTT, we employed RNA-seq to examine effects of maternal separation (MS) and environmental enrichment (EE) on striatal gene expression during development of BACHD rats. We integrated our results with striatal consensus modules defined on HTT-CAG length and age-dependent co-expression gene networks to relate the environmental factors with disease progression. While mHTT was the main determinant of expression changes, both MS and EE were capable of modulating these disturbances, resulting in distinctive and in several cases opposing effects of MS and EE on consensus modules. This bivalent response to maternal separation and environmental enrichment may aid in explaining their distinct effects observed on disease phenotypes in animal models of HD and related neurodegenerative disorders.

Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

PubMed

Chowdhury, Debashish

2013-06-04

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Control-structure interaction study for the Space Station solar dynamic power module

NASA Technical Reports Server (NTRS)

Cheng, J.; Ianculescu, G.; Ly, J.; Kim, M.

1991-01-01

The authors investigate the feasibility of using a conventional PID (proportional plus integral plus derivative) controller design to perform the pointing and tracking functions for the Space Station Freedom solar dynamic power module. Using this simple controller design, the control/structure interaction effects were also studied without assuming frequency bandwidth separation. From the results, the feasibility of a simple solar dynamic control solution with a reduced-order model, which satisfies the basic system pointing and stability requirements, is suggested. However, the conventional control design approach is shown to be very much influenced by the order of reduction of the plant model, i.e., the number of the retained elastic modes from the full-order model. This suggests that, for complex large space structures, such as the Space Station Freedom solar dynamic, the conventional control system design methods may not be adequate.

imDEV: a graphical user interface to R multivariate analysis tools in Microsoft Excel.

PubMed

Grapov, Dmitry; Newman, John W

2012-09-01

Interactive modules for Data Exploration and Visualization (imDEV) is a Microsoft Excel spreadsheet embedded application providing an integrated environment for the analysis of omics data through a user-friendly interface. Individual modules enables interactive and dynamic analyses of large data by interfacing R's multivariate statistics and highly customizable visualizations with the spreadsheet environment, aiding robust inferences and generating information-rich data visualizations. This tool provides access to multiple comparisons with false discovery correction, hierarchical clustering, principal and independent component analyses, partial least squares regression and discriminant analysis, through an intuitive interface for creating high-quality two- and a three-dimensional visualizations including scatter plot matrices, distribution plots, dendrograms, heat maps, biplots, trellis biplots and correlation networks. Freely available for download at http://sourceforge.net/projects/imdev/. Implemented in R and VBA and supported by Microsoft Excel (2003, 2007 and 2010).

Reward acts on the pFC to enhance distractor resistance of working memory representations.

PubMed

Fallon, Sean James; Cools, Roshan

2014-12-01

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

Lasing from active optomechanical resonators

PubMed Central

Czerniuk, T.; Brüggemann, C.; Tepper, J.; Brodbeck, S.; Schneider, C.; Kamp, M.; Höfling, S.; Glavin, B. A.; Yakovlev, D. R.; Akimov, A. V.; Bayer, M.

2014-01-01

Planar microcavities with distributed Bragg reflectors (DBRs) host, besides confined optical modes, also mechanical resonances due to stop bands in the phonon dispersion relation of the DBRs. These resonances have frequencies in the 10- to 100-GHz range, depending on the resonator’s optical wavelength, with quality factors exceeding 1,000. The interaction of photons and phonons in such optomechanical systems can be drastically enhanced, opening a new route towards the manipulation of light. Here we implemented active semiconducting layers into the microcavity to obtain a vertical-cavity surface-emitting laser (VCSEL). Thereby, three resonant excitations—photons, phonons and electrons—can interact strongly with each other providing modulation of the VCSEL laser emission: a picosecond strain pulse injected into the VCSEL excites long-living mechanical resonances therein. As a result, modulation of the lasing intensity at frequencies up to 40 GHz is observed. From these findings, prospective applications of active optomechanical resonators integrated into nanophotonic circuits may emerge. PMID:25008784

GASP- GENERAL AVIATION SYNTHESIS PROGRAM

NASA Technical Reports Server (NTRS)

Galloway, T. L.

1994-01-01

The General Aviation Synthesis Program, GASP, was developed to perform tasks generally associated with the preliminary phase of aircraft design. GASP gives the analyst the capability of performing parametric studies in a rapid manner during preliminary design efforts. During the development of GASP, emphasis was placed on small fixed-wing aircraft employing propulsion systems varying from a single piston engine with a fixed pitch propeller through twin turboprop/turbofan systems as employed in business or transport type aircraft. The program is comprised of modules representing the various technical disciplines of design, integrated into a computational flow which ensures that the interacting effects of design variables are continuously accounted for in the aircraft sizing procedures. GASP provides a useful tool for comparing configurations, assessing aircraft performance and economics, and performing tradeoff and sensitivity studies. By utilizing GASP, the impact of various aircraft requirements and design factors may be studied in a systematic manner, with benefits being measured in terms of overall aircraft performance and economics. The GASP program consists of a control module and six "technology" submodules which perform the various independent studies required in the design of general aviation or small transport type aircraft. The six technology modules include geometry, aerodynamics, propulsion, weight and balance, mission analysis, and economics. The geometry module calculates the dimensions of the synthesized aircraft components based on such input parameters as number of passengers, aspect ratio, taper ratio, sweep angles, and thickness of wing and tail surfaces. The aerodynamics module calculates the various lift and drag coefficients of the synthesized aircraft based on inputs concerning configuration geometry, flight conditions, and type of high lift device. The propulsion module determines the engine size and performance for the synthesized aircraft. Both cruise and take-off requirements for the aircraft may be specified. This module can currently simulate turbojet, turbofan, turboprop, and reciprocating or rotating combustion engines. The weight and balance module accepts as input gross weight, payload, aircraft geometry, and weight trend coefficients for use in calculating the size of tip tanks and wing location required such that the synthesized aircraft is in balance for center of gravity travel. In the mission analysis module, the taxi, take-off, climb, cruise, and landing segments of a specified mission are analyzed to compute the total range, and the aircraft size required to provide this range is determined. In the economic module both the flyaway and operating costs are determined from estimated resources and services cost. The six technology modules are integrated into a single synthesis system by the control module. This integrated approach ensures that the results from each module contain the effect of design interactions among all the modules. Starting from a set of simple input quantities concerning aircraft type, size, and performance, the synthesis is extended to the point where all of the important aircraft characteristics have been analyzed quantitatively. Together, the synthesis model and procedure develops aircraft configurations in a manner useful in parametric analysis and provides a useful step toward more detailed analytical and experimental studies. The GASP program is written in FORTRAN IV for batch execution and has been implemented on a CDC CYBER 170 series computer with a central memory requirement of approximately 200K(octal) of 60 bit words. The GASP program was developed in 1978.

Interactive Learning Program (ILP)- a concept for life long learning and Capacity Building of Stakeholders in Integrated Flood Management (IFM)

NASA Astrophysics Data System (ADS)

Pasche, E.; Manojlovic, N.; Basener, S.; Behzadnia, N.

2009-04-01

In the paradigm shift in flood management from traditional to more integrated approach the key to initialising this transition stage is capacity building of stakeholders. It supports the effective participation of stakeholders within their role by giving the individuals/professionals and institutions required knowledge and skills. Such a process of empowering targeted stakeholder groups should be based on the interactive learning rather than mere delivering of flood related information. It can be achieved by initiating the learning process and developing life-long learning programs in form of blended learning that combines both, supervised online and face-to-face approaches. The learning concept based on the didactic principle of Kolb/Fry, has been used as a basis for development of the Interactive Learning Program (ILP) presented in this paper. Kolb/Fry define learning as a cyclic process dividing it into four steps: concrete experience, reflection & observation, forming abstract concepts, testing of acquainted knowledge in new situations. As the knowledge to understand the complexity of IFM is extensive and required level usually cannot be achieved within the face-to-face phase, additional autodidactic learning module tailored to the individual skills should be included in the learning program. ILP combines both, the face-to-face sessions following the Kolb?s learning cycle including theoretical and practical aspects and autodidactic phase by means of the e-learning platform based on the web dissemination strategy for IFM- Kalypso Inform (Pasche/Kraus/Manojlovic). According to this strategy, the access to the flood related information is enabled through three different modules Tutorial, Knowledge Base and Virtual Trainer enabling interaction with the system. This ILP is generic and can be tailored to requirements of different stakeholder groups depending on their role and level of integration in IFM. The first results, obtained for both public and private stakeholders, are encouraging indicating that such concepts should become a substantial part of the IFM.

New Materials for the Undergraduate Classroom to Build Pre-Service Teachers' NGSS Skills and Knowledge

NASA Astrophysics Data System (ADS)

Egger, A. E.; Awad, A. A.; Baldwin, K. A.; Birnbaum, S. J.; Bruckner, M. Z.; DeBari, S. M.; Dechaine, J.; Ebert, J. R.; Gray, K. R.; Hauge, R.; Linneman, S. R.; Monet, J.; Thomas, J.; Varrella, G.

2014-12-01

As part of InTeGrate, teams of 3 instructors at 3 different institutions developed modules that help prepare pre-service teachers to teach Earth science aligned with the NGSS. Modules were evaluated against a rubric, which addresses InTeGrate's five guiding principles, learning objectives and outcomes, assessment and measurement, resources and materials, instructional strategies and alignment. As all modules must address one or more Earth-related grand challenge facing society, develop student ability to address interdisciplinary problems, improve student understanding of the methods of geoscience, use authentic geoscience data, and incorporate systems thinking, they align well with the NGSS. Once modules passed the rubric, they were tested by the authors in their classrooms. Testing included pre- and post-assessment of geoscience literacy and assessment of student learning towards the module goal; materials were revised based on the results of testing. In "Exploring Geoscience Methods with Secondary Education Students," pre-service science teachers compare geoscientific thinking with the classic (experimental) scientific method, investigate global climate change and its impacts on human systems, and prepare an interdisciplinary lesson plan that addresses geoscience methods in context of a socioscientific issue. In "Soils and Society," pre-service elementary teachers explore societal issues where soil is important, develop skills to describe and test soil properties, and create a standards-based Soils and Society Kit that consists of lessons and supporting materials to teach K-8 students about a soil-and-society issue. In "Interactions between Water, Earth's Surface, and Human Activity," students explore the effects of running water on shaping Earth's surface both over geologic time and through short-term flooding events, and produce a brochure to inform citizens of the impact of living near a river. The modules are freely available at http://serc.carleton.edu/integrate/teaching_materials/modules_courses.html and include Instructor Stories, where each author describes how they adapted the module to their teaching environment. The goal of showing different implementations of the materialst is to facilitate adoption and adaption beyond the team of authors.

Phase precession through acceleration of local theta rhythm: a biophysical model for the interaction between place cells and local inhibitory neurons.

PubMed

Castro, Luísa; Aguiar, Paulo

2012-08-01

Phase precession is one of the most well known examples within the temporal coding hypothesis. Here we present a biophysical spiking model for phase precession in hippocampal CA1 which focuses on the interaction between place cells and local inhibitory interneurons. The model's functional block is composed of a place cell (PC) connected with a local inhibitory cell (IC) which is modulated by the population theta rhythm. Both cells receive excitatory inputs from the entorhinal cortex (EC). These inputs are both theta modulated and space modulated. The dynamics of the two neuron types are described by integrate-and-fire models with conductance synapses, and the EC inputs are described using non-homogeneous Poisson processes. Phase precession in our model is caused by increased drive to specific PC/IC pairs when the animal is in their place field. The excitation increases the IC's firing rate, and this modulates the PC's firing rate such that both cells precess relative to theta. Our model implies that phase coding in place cells may not be independent from rate coding. The absence of restrictive connectivity constraints in this model predicts the generation of phase precession in any network with similar architecture and subject to a clocking rhythm, independently of the involvement in spatial tasks.

Evaluation of an Interactive Undergraduate Cosmology Curriculum

NASA Astrophysics Data System (ADS)

White, Aaron; Coble, Kimberly A.; Martin, Dominique; Hayes, Patrycia; Targett, Tom; Cominsky, Lynn R.

2018-06-01

The Big Ideas in Cosmology is an immersive set of web-based learning modules that integrates text, figures, and visualizations with short and long interactive tasks as well as labs that allow students to manipulate and analyze real cosmological data. This enables the transformation of general education astronomy and cosmology classes from primarily lecture and book-based courses to a format that builds important STEM skills, while engaging those outside the field with modern discoveries and a more realistic sense of practices and tools used by professional astronomers. Over two semesters, we field-tested the curriculum in general education cosmology classes at a state university in California [N ~ 80]. We administered pre- and post-instruction multiple-choice and open-ended content surveys as well as the CLASS, to gauge the effectiveness of the course and modules. Questions addressed included the structure, composition, and evolution of the universe, including students’ reasoning and “how we know.”Module development and evaluation was supported by NASA ROSES E/PO Grant #NNXl0AC89G, the Illinois Space Grant Consortium, the Fermi E/PO program, Sonoma State University’s Space Science Education and Public Outreach Group, and San Francisco State University. The modules are published by Great River Learning/Kendall-Hunt.

Integration of Multifidelity Multidisciplinary Computer Codes for Design and Analysis of Supersonic Aircraft

NASA Technical Reports Server (NTRS)

Geiselhart, Karl A.; Ozoroski, Lori P.; Fenbert, James W.; Shields, Elwood W.; Li, Wu

2011-01-01

This paper documents the development of a conceptual level integrated process for design and analysis of efficient and environmentally acceptable supersonic aircraft. To overcome the technical challenges to achieve this goal, a conceptual design capability which provides users with the ability to examine the integrated solution between all disciplines and facilitates the application of multidiscipline design, analysis, and optimization on a scale greater than previously achieved, is needed. The described capability is both an interactive design environment as well as a high powered optimization system with a unique blend of low, mixed and high-fidelity engineering tools combined together in the software integration framework, ModelCenter. The various modules are described and capabilities of the system are demonstrated. The current limitations and proposed future enhancements are also discussed.

[Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)].

PubMed

Kuznetsov, S V; Sizonov, V A; Dmitrieva, L E

2014-01-01

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the intersystemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and many-minute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason--are weakly enhanced.

IAC - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Frisch, H. P.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. With the goal of supporting the unique needs of engineering analysis groups concerned with interdisciplinary problems, IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a data base, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automatic data transfer among analysis programs. IAC 2.5, designed to be compatible as far as possible with Level 1.5, contains a major upgrade in executive and database management system capabilities, and includes interfaces to enable thermal, structures, optics, and control interaction dynamics analysis. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation interfaces are supplied for building and viewing models. Advanced graphics capabilities are provided within particular analysis modules such as INCA and NASTRAN. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files, object code, etc. The user can define groups of data and relations between them. A full data manipulation and query system operates with the database. The current interface modules comprise five groups: 1) Structural analysis - IAC contains a NASTRAN interface for standalone analysis or certain structural/control/thermal combinations. IAC provides enhanced structural capabilities for normal modes and static deformation analysis via special DMAP sequences. IAC 2.5 contains several specialized interfaces from NASTRAN in support of multidisciplinary analysis. 2) Thermal analysis - IAC supports finite element and finite difference techniques for steady state or transient analysis. There are interfaces for the NASTRAN thermal analyzer, SINDA/SINFLO, and TRASYS II. FEMNET, which converts finite element structural analysis models to finite difference thermal analysis models, is also interfaced with the IAC database. 3) System dynamics - The DISCOS simulation program which allows for either nonlinear time domain analysis or linear frequency domain analysis, is fully interfaced to the IAC database management capability. 4) Control analysis - Interfaces for the ORACLS, SAMSAN, NBOD2, and INCA programs allow a wide range of control system analyses and synthesis techniques. Level 2.5 includes EIGEN, which provides tools for large order system eigenanalysis, and BOPACE, which allows for geometric capabilities and finite element analysis with nonlinear material. Also included in IAC level 2.5 is SAMSAN 3.1, an engineering analysis program which contains a general purpose library of over 600 subroutin

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

PubMed

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Pelagic Habitat Analysis Module (PHAM) for GIS Based Fisheries Decision Support

NASA Technical Reports Server (NTRS)

Kiefer, D. A.; Armstrong, Edward M.; Harrison, D. P.; Hinton, M. G.; Kohin, S.; Snyder, S.; O'Brien, F. J.

2011-01-01

We have assembled a system that integrates satellite and model output with fisheries data We have developed tools that allow analysis of the interaction between species and key environmental variables Demonstrated the capacity to accurately map habitat of Thresher Sharks Alopias vulpinus & pelagicus. Their seasonal migration along the California Current is at least partly driven by the seasonal migration of sardine, key prey of the sharks.We have assembled a system that integrates satellite and model output with fisheries data We have developed tools that allow analysis of the interaction between species and key environmental variables Demonstrated the capacity to accurately map habitat of Thresher Sharks Alopias vulpinus nd pelagicus. Their seasonal migration along the California Current is at least partly driven by the seasonal migration of sardine, key prey of the sharks.

Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network.

PubMed

Sun, Shuguo; Irvine, Kenneth D

2016-09-01

The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated and to define their respective contributions in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apparatus and method for interaction phenomena with world modules in data-flow-based simulation

DOEpatents

Xavier, Patrick G [Albuquerque, NM; Gottlieb, Eric J [Corrales, NM; McDonald, Michael J [Albuquerque, NM; Oppel, III, Fred J.

2006-08-01

A method and apparatus accommodate interaction phenomenon in a data-flow-based simulation of a system of elements, by establishing meta-modules to simulate system elements and by establishing world modules associated with interaction phenomena. World modules are associated with proxy modules from a group of meta-modules associated with one of the interaction phenomenon. The world modules include a communication world, a sensor world, a mobility world, and a contact world. World modules can be further associated with other world modules if necessary. Interaction phenomenon are simulated in corresponding world modules by accessing member functions in the associated group of proxy modules. Proxy modules can be dynamically allocated at a desired point in the simulation to accommodate the addition of elements in the system of elements such as a system of robots, a system of communication terminals, or a system of vehicles, being simulated.

ZikaBase: An integrated ZIKV- Human Interactome Map database.

PubMed

Gurumayum, Sanathoi; Brahma, Rahul; Naorem, Leimarembi Devi; Muthaiyan, Mathavan; Gopal, Jeyakodi; Venkatesan, Amouda

2018-01-15

Re-emergence of ZIKV has caused infections in more than 1.5 million people. The molecular mechanism and pathogenesis of ZIKV is not well explored due to unavailability of adequate model and lack of publically accessible resources to provide information of ZIKV-Human protein interactome map till today. This study made an attempt to curate the ZIKV-Human interaction proteins from published literatures and RNA-Seq data. 11 direct interaction, 12 associated genes are retrieved from literatures and 3742 Differentially Expressed Genes (DEGs) are obtained from RNA-Seq analysis. The genes have been analyzed to construct the ZIKV-Human Interactome Map. The importance of the study has been illustrated by the enrichment analysis and observed that direct interaction and associated genes are enriched in viral entry into host cell. Also, ZIKV infection modulates 32% signal and 27% immune system pathways. The integrated database, ZikaBase has been developed to help the virology research community and accessible at https://test5.bicpu.edu.in. Copyright © 2017 Elsevier Inc. All rights reserved.

InteractInteraction mechanism of emergency response in geological hazard perception and risk management: a case study in Zhouqu county

NASA Astrophysics Data System (ADS)

Qi, Yuan; Zhao, Hongtao

2017-04-01

China is one of few several natural disaster prone countries, which has complex geological and geographical environment and abnormal climate. On August 8, 2010, a large debris flow disaster happened in Zhouqu Country, Gansu province, resulting in more than 1700 casualties and more than 200 buildings damaged. In order to percept landslide and debris flow, an early warning system was established in the county. Spatial information technologies, such as remote sensing, GIS, and GPS, play core role in the early warning system, due to their functions in observing, analyzing, and locating geological disasters. However, all of these spatial information technologies could play an important role only guided by the emergency response mechanism. This article takes the establishment of Zhouqu Country's Disaster Emergency Response Interaction Mechanism (DERIM) as an example to discuss the risk management of country-level administrative units. The country-level risk management aims to information sharing, resources integration, integrated prevention and unified command. Then, nine subsystems support DERIM, which included disaster prevention and emergency data collection and sharing system, joint duty system, disaster verification and evaluation system, disaster consultation system, emergency warning and information release system, emergency response system, disaster reporting system, plan management system, mass prediction and prevention management system. At last, an emergency command platform in Zhouqu Country built up to realize DERIM. The core mission of the platform consists of daily management of disaster, monitoring and warning, comprehensive analysis, information release, consultation and decision-making, emergency response, etc. Five functional modules, including module of disaster information management, comprehensive monitoring module (geological monitoring, meteorological monitoring, water conservancy and hydrological monitoring), alarm management module, emergency command and disaster dispatching management module are developed on the basis of this platform. Based on the internet technology, an web-based office platform is exploited for the nodes scattered in departments and towns, which includes daily business, monitoring and warning, alarm notification, alarm recording, personnel management and update in disaster region, query and analysis of real-time observation data, etc. The platform experienced 3 years' test of the duty in flood period since 2013, and two typical disaster cases during this period fully illustrates the effectiveness of the DERIM and the emergency command platform.

Integrated metagenomic analysis of the rumen microbiome of cattle reveals key biological mechanisms associated with methane traits.

PubMed

Wang, Haiying; Zheng, Huiru; Browne, Fiona; Roehe, Rainer; Dewhurst, Richard J; Engel, Felix; Hemmje, Matthias; Lu, Xiangwu; Walsh, Paul

2017-07-15

Methane is one of the major contributors to global warming. The rumen microbiota is directly involved in methane production in cattle. The link between variation in rumen microbial communities and host genetics has important applications and implications in bioscience. Having the potential to reveal the full extent of microbial gene diversity and complex microbial interactions, integrated metagenomics and network analysis holds great promise in this endeavour. This study investigates the rumen microbial community in cattle through the integration of metagenomic and network-based approaches. Based on the relative abundance of 1570 microbial genes identified in a metagenomics analysis, the co-abundance network was constructed and functional modules of microbial genes were identified. One of the main contributions is to develop a random matrix theory-based approach to automatically determining the correlation threshold used to construct the co-abundance network. The resulting network, consisting of 549 microbial genes and 3349 connections, exhibits a clear modular structure with certain trait-specific genes highly over-represented in modules. More specifically, all the 20 genes previously identified to be associated with methane emissions are found in a module (hypergeometric test, p<10 -11 ). One third of genes are involved in methane metabolism pathways. The further examination of abundance profiles across 8 samples of genes highlights that the revealed pattern of metagenomics abundance has a strong association with methane emissions. Furthermore, the module is significantly enriched with microbial genes encoding enzymes that are directly involved in methanogenesis (hypergeometric test, p<10 -9 ). Copyright © 2017 Elsevier Inc. All rights reserved.

On the concept of the interactive information and simulation system for gas dynamics and multiphysics problems

NASA Astrophysics Data System (ADS)

Bessonov, O.; Silvestrov, P.

2017-02-01

This paper describes the general idea and the first implementation of the Interactive information and simulation system - an integrated environment that combines computational modules for modeling the aerodynamics and aerothermodynamics of re-entry space vehicles with the large collection of different information materials on this topic. The internal organization and the composition of the system are described and illustrated. Examples of the computational and information output are presented. The system has the unified implementation for Windows and Linux operation systems and can be deployed on any modern high-performance personal computer.

Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains

PubMed Central

Rungaldier, Stefanie; Oberwagner, Walter; Salzer, Ulrich; Csaszar, Edina; Prohaska, Rainer

2013-01-01

The widely expressed, homo-oligomeric, lipid raft-associated, monotopic integral membrane protein stomatin and its homologues are known to interact with and modulate various ion channels and transporters. Stomatin is a major protein of the human erythrocyte membrane, where it associates with and modifies the glucose transporter GLUT1; however, previous attempts to purify hetero-oligomeric stomatin complexes for biochemical analysis have failed. Because lateral interactions of membrane proteins may be short-lived and unstable, we have used in situ chemical cross-linking of erythrocyte membranes to fix the stomatin complexes for subsequent purification by immunoaffinity chromatography. To further enrich stomatin, we prepared detergent-resistant membranes either before or after cross-linking. Mass spectrometry of the isolated, high molecular, cross-linked stomatin complexes revealed the major interaction partners as glucose transporter-1 (GLUT1), anion exchanger (band 3), and water channel (aquaporin-1). Moreover, ferroportin-1 (SLC40A1), urea transporter-1 (SLC14A1), nucleoside transporter (SLC29A1), the calcium-pump (Ca-ATPase-4), CD47, and flotillins were identified as stomatin-interacting proteins. These findings are in line with the hypothesis that stomatin plays a role as membrane-bound scaffolding protein modulating transport proteins. PMID:23219802

Medio-lateral postural instability in subjects with tinnitus.

PubMed

Kapoula, Zoi; Yang, Qing; Lê, Thanh-Thuan; Vernet, Marine; Berbey, Nolwenn; Orssaud, Christophe; Londero, Alain; Bonfils, Pierre

2011-01-01

Many patients show modulation of tinnitus by gaze, jaw or neck movements, reflecting abnormal sensorimotor integration, and interaction between various inputs. Postural control is based on multi-sensory integration (visual, vestibular, somatosensory, and oculomotor) and indeed there is now evidence that posture can also be influenced by sound. Perhaps tinnitus influences posture similarly to external sound. This study examines the quality of postural performance in quiet stance in patients with modulated tinnitus. Twenty-three patients with highly modulated tinnitus were selected in the ENT service. Twelve reported exclusively or predominately left tinnitus, eight right, and three bilateral. Eighteen control subjects were also tested. Subjects were asked to fixate a target at 40 cm for 51 s; posturography was performed with the platform (Technoconcept, 40 Hz) for both the eyes open and eyes closed conditions. For both conditions, tinnitus subjects showed abnormally high lateral body sway (SDx). This was corroborated by fast Fourrier Transformation (FFTx) and wavelet analysis. For patients with left tinnitus only, medio-lateral sway increased significantly when looking away from the center. Similarly to external sound stimulation, tinnitus could influence lateral sway by activating attention shift, and perhaps vestibular responses. Poor integration of sensorimotor signals is another possibility. Such abnormalities would be accentuated in left tinnitus because of the importance of the right cerebral cortex in processing both auditory-tinnitus eye position and attention.

The Comparative Toxicogenomics Database: update 2017.

PubMed

Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J; Sciaky, Daniela; King, Benjamin L; McMorran, Roy; Wiegers, Jolene; Wiegers, Thomas C; Mattingly, Carolyn J

2017-01-04

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules. In this update, we report a 33% increase in our core data content since 2015, describe our new exposure module (that harmonizes exposure science information with core toxicogenomic data) and introduce a novel dataset of GO-disease inferences (that identify common molecular underpinnings for seemingly unrelated pathologies). These advancements centralize and contextualize real-world chemical exposures with molecular pathways to help scientists generate testable hypotheses in an effort to understand the etiology and mechanisms underlying environmentally influenced diseases. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

A modular modulation method for achieving increases in metabolite production.

PubMed

Acerenza, Luis; Monzon, Pablo; Ortega, Fernando

2015-01-01

Increasing the production of overproducing strains represents a great challenge. Here, we develop a modular modulation method to determine the key steps for genetic manipulation to increase metabolite production. The method consists of three steps: (i) modularization of the metabolic network into two modules connected by linking metabolites, (ii) change in the activity of the modules using auxiliary rates producing or consuming the linking metabolites in appropriate proportions and (iii) determination of the key modules and steps to increase production. The mathematical formulation of the method in matrix form shows that it may be applied to metabolic networks of any structure and size, with reactions showing any kind of rate laws. The results are valid for any type of conservation relationships in the metabolite concentrations or interactions between modules. The activity of the module may, in principle, be changed by any large factor. The method may be applied recursively or combined with other methods devised to perform fine searches in smaller regions. In practice, it is implemented by integrating to the producer strain heterologous reactions or synthetic pathways producing or consuming the linking metabolites. The new procedure may contribute to develop metabolic engineering into a more systematic practice. © 2015 American Institute of Chemical Engineers.

Activities, Animations, and Online Tools to Enable Undergraduate Student Learning of Geohazards, Climate Change, and Water Resources

NASA Astrophysics Data System (ADS)

Pratt-Sitaula, B. A.; Walker, B.; Douglas, B. J.; Cronin, V. S.; Funning, G.; Stearns, L. A.; Charlevoix, D.; Miller, M. M.

2017-12-01

The NSF-funded GEodesy Tools for Societal Issues (GETSI) project is developing teaching resources for use in introductory and majors-level courses, emphasizing a broad range of geodetic methods and data applied to societally important issues. The modules include a variety of hands-on activities, demonstrations, animations, and interactive online tools in order to facilitate student learning and engagement. A selection of these activities will be showcased at the AGU session. These activities and data analysis exercises are embedded in 4-6 units per module. Modules can take 2-3 weeks of course time total or individual units and activities can be selected and used over just 1-2 class periods. Existing modules are available online via serc.carleton.edu/getsi/ and include "Ice mass and sea level changes", "Imaging active tectonics with LiDAR and InSAR", "Measuring water resources with GPS, gravity, and traditional methods", "Surface process hazards", and "GPS, strain, and earthquakes". Modules, and their activities and demonstrations were designed by teams of faculty and content experts and underwent rigorous classroom testing and review using the process developed by the Science Education Resource Center's InTeGrate Project (serc.carleton.edu/integrate). All modules are aligned to Earth Science and Climate literacy principles. GETSI collaborating institutions are UNAVCO (which runs NSF's Geodetic Facility), Indiana University, and Mt San Antonio College. Initial funding came from NSF's TUES (Transforming Undergraduate Education in STEM). A second phase of funding from NSF IUSE (Improving Undergraduate STEM Education) is just starting and will fund another six modules (including their demonstrations, activities, and hands-on activities) as well as considerably more instructor professional development to facilitate implementation and use.

Light Microscopy Module Imaging Tested and Demonstrated

NASA Technical Reports Server (NTRS)

Gati, Frank

2004-01-01

The Fluids Integrated Rack (FIR), a facility-class payload, and the Light Microscopy Module (LMM), a subrack payload, are integrated research facilities that will fly in the U.S. Laboratory module, Destiny, aboard the International Space Station. Both facilities are being engineered, designed, and developed at the NASA Glenn Research Center by Northrop Grumman Information Technology. The FIR is a modular, multiuser scientific research facility that is one of two racks that make up the Fluids and Combustion Facility (the other being the Combustion Integrated Rack). The FIR has a large volume dedicated for experimental hardware; easily reconfigurable diagnostics, power, and data systems that allow for unique experiment configurations; and customizable software. The FIR will also provide imagers, light sources, power management and control, command and data handling for facility and experiment hardware, and data processing and storage. The first payload in the FIR will be the LMM. The LMM integrated with the FIR is a remotely controllable, automated, on-orbit microscope subrack facility, with key diagnostic capabilities for meeting science requirements--including video microscopy to observe microscopic phenonema and dynamic interactions, interferometry to make thin-film measurements with nanometer resolution, laser tweezers to manipulate micrometer-sized particles, confocal microscopy to provide enhanced three-dimensional visualization of structures, and spectrophotometry to measure the photonic properties of materials. Vibration disturbances were identified early in the LMM development phase as a high risk for contaminating the science microgravity environment. An integrated FIR-LMM test was conducted in Glenn's Acoustics Test Laboratory to assess mechanical sources of vibration and their impact to microscopic imaging. The primary purpose of the test was to characterize the LMM response at the sample location, the x-y stage within the microscope, to vibration emissions from the FIR and LMM support structures.

Structural basis for KCNE3 modulation of potassium recycling in epithelia.

PubMed

Kroncke, Brett M; Van Horn, Wade D; Smith, Jarrod; Kang, CongBao; Welch, Richard C; Song, Yuanli; Nannemann, David P; Taylor, Keenan C; Sisco, Nicholas J; George, Alfred L; Meiler, Jens; Vanoye, Carlos G; Sanders, Charles R

2016-09-01

The single-span membrane protein KCNE3 modulates a variety of voltage-gated ion channels in diverse biological contexts. In epithelial cells, KCNE3 regulates the function of the KCNQ1 potassium ion (K(+)) channel to enable K(+) recycling coupled to transepithelial chloride ion (Cl(-)) secretion, a physiologically critical cellular transport process in various organs and whose malfunction causes diseases, such as cystic fibrosis (CF), cholera, and pulmonary edema. Structural, computational, biochemical, and electrophysiological studies lead to an atomically explicit integrative structural model of the KCNE3-KCNQ1 complex that explains how KCNE3 induces the constitutive activation of KCNQ1 channel activity, a crucial component in K(+) recycling. Central to this mechanism are direct interactions of KCNE3 residues at both ends of its transmembrane domain with residues on the intra- and extracellular ends of the KCNQ1 voltage-sensing domain S4 helix. These interactions appear to stabilize the activated "up" state configuration of S4, a prerequisite for full opening of the KCNQ1 channel gate. In addition, the integrative structural model was used to guide electrophysiological studies that illuminate the molecular basis for how estrogen exacerbates CF lung disease in female patients, a phenomenon known as the "CF gender gap."

V-band integrated quadriphase modulator

NASA Technical Reports Server (NTRS)

Grote, A.; Chang, K.

1983-01-01

A V-band integrated circuit quadriphase shift keyed modulator/exciter for space communications systems was developed. Intersatellite communications systems require direct modulation at 60 GHz to enhance signal processing capability. For most systems, particularly space applications, small and lightweight components are essential to alleviate severe system design constraints. Thus to achieve wideband, high data rate systems, direct modulation techniques at millimeter waves using solid state integrated circuit technology are an integral part of the overall technology developments.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

Cosmic ray modulation and merged interaction regions

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Goldstein, M. L.; Mcdonald, F. B.

1985-01-01

Beyond several AU, interactions among shocks and streams give rise to merged interaction regions in which the magnetic field is turbulent. The integral intensity of . 75 MeV/Nuc cosmic rays at Voyager is generally observed to decrease when a merged interaction region moves past the spacecraft and to increase during the passage of a rarefaction region. When the separation between interaction regions is relatively large, the cosmic ray intensity tends to increase on a scale of a few months. This was the case at Voyager 1 from July 1, 1983 to May 1, 1984, when the spacecraft moved from 16.7 to 19.6 AU. Changes in cosmic ray intensity were related to the magnetic field strength in a simple way. It is estimated that the diffusion coefficient in merged interaction regions at this distance is similar to 0.6 x 10 to the 22nd power sq cm/s.

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer.

PubMed

Yang, Mary Qu; Li, Dan; Yang, William; Zhang, Yifan; Liu, Jun; Tong, Weida

2017-01-01

Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1 , as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways.

The N-Terminus of Vps74p Is Essential for the Retention of Glycosyltransferases in the Golgi but Not for the Modulation of Apical Polarized Growth in Saccharomyces cerevisiae

PubMed Central

Huang, Chun-Fang; Lee, Fang-Jen S.

2013-01-01

Vps74p is a member of the PtdIns(4)P-binding protein family. Vps74p interacts with Golgi-resident glycosyltransferases and the coat protein COPI complex to modulate Golgi retention of glycosyltransferases and with the PtdIns(4)P phosphatase Sac1p to modulate PtdIns(4)P homeostasis at the Golgi. Genetic analysis has shown that Vps74p is required for the formation of abnormal elongated buds in cdc34-2 cells. The C-terminal region of Vps74p is required for Vps74p multimerization, Golgi localization, and glycosyltransferase interactions; however, the functional significance of the N-terminal region and three putative phosphorylation sites of Vps74p have not been well characterized. In this study, we demonstrate that Vps74p executes multiple cellular functions using different domains. We found that the N-terminal 66 amino acids of Vps74p are dispensable for its Golgi localization and modulation of cell wall integrity but are required for glycosyltransferase retention and glycoprotein processing. Deletion of the N-terminal 90 amino acids, but not the 66 amino acids, of Vps74p impaired its ability to restore the elongated bud phenotype in cdc34-2/vps74Δ cells. Deletion of Sac1p and Arf1p also specifically reduced the abnormal elongated bud phenotype in cdc34-2 cells. Furthermore, we found that three N-terminal phosphorylation sites contribute to rapamycin hypersensitivity, although these phosphorylation residues are not involved in Vps74p localization, ability to modulate glycosyltransferase retention, or elongated bud formation in cdc34-2 cells. Thus, we propose that Vps74p may use different domains to interact with specific effectors thereby differentially modulating a variety of cellular functions. PMID:24019977

Modulation in prototropism of the photosensitizer Harmane by host:guest interactions between β-cyclodextrin and surfactants.

PubMed

Paul, Bijan K; Ray, Debarati; Ganguly, Aniruddha; Guchhait, Nikhil

2013-12-01

The present contribution demonstrates the photophysics of a prospective cancer cell photosensitizer Harmane (HM) belonging to the family of β-carboline in mixed microheterogeneous environments of β-cyclodextrin (β-CD) and surfactants having varying surface charges using steady-state and time-resolved fluorescence spectroscopic techniques. The remarkable modulations in prototropic activities of the micelle-bound drug in the presence of β-CD evinces for disruption of the micellar structural integrity by β-CD. The results are meticulously discussed in relevance to the effect of a potential drug delivery vehicle (CD) on the membrane-mimetic micellar system. Further, application of an extrinsic fluorescence probe for monitoring such interactions is fraught by the possibilities of no less than three equilibria that can operate simultaneously viz., (i) surfactant-cyclodextrin, (ii) surfactant-fluorophore and (iii) cyclodextrin-fluorophore. This aspect highlights the enormous importance of the issue of suitability of the fluorescence probe to study such complicated systems and interaction phenomena. Also the varying interaction scenario of β-CD with the nature of the surfactant highlights the importance of precise knowledge of the strength and locus of drug binding in delineating such complex interactions. The results of the present investigation advocate for the potential applicability of the drug (HM) itself as a fluorescence reporter in study of such complex microheterogeneous interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of IAC in large space systems thermal analysis

NASA Technical Reports Server (NTRS)

Jones, G. K.; Skladany, J. T.; Young, J. P.

1982-01-01

Computer analysis programs to evaluate critical coupling effects that can significantly influence spacecraft system performance are described. These coupling effects arise from the varied parameters of the spacecraft systems, environments, and forcing functions associated with disciplines such as thermal, structures, and controls. Adverse effects can be expected to significantly impact system design aspects such as structural integrity, controllability, and mission performance. One such needed design analysis capability is a software system that can integrate individual discipline computer codes into a highly user-oriented/interactive-graphics-based analysis capability. The integrated analysis capability (IAC) system can be viewed as: a core framework system which serves as an integrating base whereby users can readily add desired analysis modules and as a self-contained interdisciplinary system analysis capability having a specific set of fully integrated multidisciplinary analysis programs that deal with the coupling of thermal, structures, controls, antenna radiation performance, and instrument optical performance disciplines.

Predicting rates of interspecific interaction from phylogenetic trees.

PubMed

Nuismer, Scott L; Harmon, Luke J

2015-01-01

Integrating phylogenetic information can potentially improve our ability to explain species' traits, patterns of community assembly, the network structure of communities, and ecosystem function. In this study, we use mathematical models to explore the ecological and evolutionary factors that modulate the explanatory power of phylogenetic information for communities of species that interact within a single trophic level. We find that phylogenetic relationships among species can influence trait evolution and rates of interaction among species, but only under particular models of species interaction. For example, when interactions within communities are mediated by a mechanism of phenotype matching, phylogenetic trees make specific predictions about trait evolution and rates of interaction. In contrast, if interactions within a community depend on a mechanism of phenotype differences, phylogenetic information has little, if any, predictive power for trait evolution and interaction rate. Together, these results make clear and testable predictions for when and how evolutionary history is expected to influence contemporary rates of species interaction. © 2014 John Wiley & Sons Ltd/CNRS.

What We Observe Is Biased by What Other People Tell Us: Beliefs about the Reliability of Gaze Behavior Modulate Attentional Orienting to Gaze Cues

PubMed Central

Wiese, Eva; Wykowska, Agnieszka; Müller, Hermann J.

2014-01-01

For effective social interactions with other people, information about the physical environment must be integrated with information about the interaction partner. In order to achieve this, processing of social information is guided by two components: a bottom-up mechanism reflexively triggered by stimulus-related information in the social scene and a top-down mechanism activated by task-related context information. In the present study, we investigated whether these components interact during attentional orienting to gaze direction. In particular, we examined whether the spatial specificity of gaze cueing is modulated by expectations about the reliability of gaze behavior. Expectations were either induced by instruction or could be derived from experience with displayed gaze behavior. Spatially specific cueing effects were observed with highly predictive gaze cues, but also when participants merely believed that actually non-predictive cues were highly predictive. Conversely, cueing effects for the whole gazed-at hemifield were observed with non-predictive gaze cues, and spatially specific cueing effects were attenuated when actually predictive gaze cues were believed to be non-predictive. This pattern indicates that (i) information about cue predictivity gained from sampling gaze behavior across social episodes can be incorporated in the attentional orienting to social cues, and that (ii) beliefs about gaze behavior modulate attentional orienting to gaze direction even when they contradict information available from social episodes. PMID:24722348

TMEM237 Is Mutated in Individuals with a Joubert Syndrome Related Disorder and Expands the Role of the TMEM Family at the Ciliary Transition Zone

PubMed Central

Huang, Lijia; Szymanska, Katarzyna; Jensen, Victor L.; Janecke, Andreas R.; Innes, A. Micheil; Davis, Erica E.; Frosk, Patrick; Li, Chunmei; Willer, Jason R.; Chodirker, Bernard N.; Greenberg, Cheryl R.; McLeod, D. Ross; Bernier, Francois P.; Chudley, Albert E.; Müller, Thomas; Shboul, Mohammad; Logan, Clare V.; Loucks, Catrina M.; Beaulieu, Chandree L.; Bowie, Rachel V.; Bell, Sandra M.; Adkins, Jonathan; Zuniga, Freddi I.; Ross, Kevin D.; Wang, Jian; Ban, Matthew R.; Becker, Christian; Nürnberg, Peter; Douglas, Stuart; Craft, Cheryl M.; Akimenko, Marie-Andree; Hegele, Robert A.; Ober, Carole; Utermann, Gerd; Bolz, Hanno J.; Bulman, Dennis E.; Katsanis, Nicholas; Blacque, Oliver E.; Doherty, Dan; Parboosingh, Jillian S.; Leroux, Michel R.; Johnson, Colin A.; Boycott, Kym M.

2011-01-01

Joubert syndrome related disorders (JSRDs) have broad but variable phenotypic overlap with other ciliopathies. The molecular etiology of this overlap is unclear but probably arises from disrupting common functional module components within primary cilia. To identify additional module elements associated with JSRDs, we performed homozygosity mapping followed by next-generation sequencing (NGS) and uncovered mutations in TMEM237 (previously known as ALS2CR4). We show that loss of the mammalian TMEM237, which localizes to the ciliary transition zone (TZ), results in defective ciliogenesis and deregulation of Wnt signaling. Furthermore, disruption of Danio rerio (zebrafish) tmem237 expression produces gastrulation defects consistent with ciliary dysfunction, and Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and ciliogenesis. Both mammalian and C. elegans TMEM237/JBTS-14 require RPGRIP1L/MKS5 for proper TZ localization, and we demonstrate additional functional interactions between C. elegans JBTS-14 and MKS-2/TMEM216, MKSR-1/B9D1, and MKSR-2/B9D2. Collectively, our findings integrate TMEM237/JBTS-14 in a complex interaction network of TZ-associated proteins and reveal a growing contribution of a TZ functional module to the spectrum of ciliopathy phenotypes. PMID:22152675

Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

PubMed

Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

2016-06-07

Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.

Interdisciplinary Integration of the CVS Module and Its Effect on Faculty and Student Satisfaction as Well as Student Performance

PubMed Central

2012-01-01

Background Beyond the adoption of the principles of horizontal and vertical integration, significant planning and implementation of curriculum reform is needed. This study aimed to assess the effect of the interdisciplinary integrated Cardiovascular System (CVS) module on both student satisfaction and performance and comparing them to those of the temporally coordinated CVS module that was implemented in the previous year at the faculty of Medicine of the King Abdulaziz University, Saudi Arabia. Methods This interventional study used mixed method research design to assess student and faculty satisfaction with the level of integration within the CVS module. A team from the medical education department was assembled in 2010/2011 to design a plan to improve the CVS module integration level. After delivering the developed module, both student and faculty satisfaction as well as students performance were assessed and compared to those of the previous year to provide an idea about module effectiveness. Results Many challenges faced the medical education team during design and implementation of the developed CVS module e.g. resistance of faculty members to change, increasing the percentage of students directed learning hours from the total contact hour allotted to the module and shifting to integrated item writing in students assessment, spite of that the module achieved a significant increase in both teaching faculty and student satisfaction as well as in the module scores. Conclusion The fully integrated CVS has yielded encouraging results that individual teachers or other medical schools who attempt to reformulate their curriculum may find valuable. PMID:22747781

Visual Distractors Disrupt Audiovisual Integration Regardless of Stimulus Complexity

PubMed Central

Gibney, Kyla D.; Aligbe, Enimielen; Eggleston, Brady A.; Nunes, Sarah R.; Kerkhoff, Willa G.; Dean, Cassandra L.; Kwakye, Leslie D.

2017-01-01

The intricate relationship between multisensory integration and attention has been extensively researched in the multisensory field; however, the necessity of attention for the binding of multisensory stimuli remains contested. In the current study, we investigated whether diverting attention from well-known multisensory tasks would disrupt integration and whether the complexity of the stimulus and task modulated this interaction. A secondary objective of this study was to investigate individual differences in the interaction of attention and multisensory integration. Participants completed a simple audiovisual speeded detection task and McGurk task under various perceptual load conditions: no load (multisensory task while visual distractors present), low load (multisensory task while detecting the presence of a yellow letter in the visual distractors), and high load (multisensory task while detecting the presence of a number in the visual distractors). Consistent with prior studies, we found that increased perceptual load led to decreased reports of the McGurk illusion, thus confirming the necessity of attention for the integration of speech stimuli. Although increased perceptual load led to longer response times for all stimuli in the speeded detection task, participants responded faster on multisensory trials than unisensory trials. However, the increase in multisensory response times violated the race model for no and low perceptual load conditions only. Additionally, a geometric measure of Miller’s inequality showed a decrease in multisensory integration for the speeded detection task with increasing perceptual load. Surprisingly, we found diverging changes in multisensory integration with increasing load for participants who did not show integration for the no load condition: no changes in integration for the McGurk task with increasing load but increases in integration for the detection task. The results of this study indicate that attention plays a crucial role in multisensory integration for both highly complex and simple multisensory tasks and that attention may interact differently with multisensory processing in individuals who do not strongly integrate multisensory information. PMID:28163675

Visual Distractors Disrupt Audiovisual Integration Regardless of Stimulus Complexity.

PubMed

Gibney, Kyla D; Aligbe, Enimielen; Eggleston, Brady A; Nunes, Sarah R; Kerkhoff, Willa G; Dean, Cassandra L; Kwakye, Leslie D

2017-01-01

The intricate relationship between multisensory integration and attention has been extensively researched in the multisensory field; however, the necessity of attention for the binding of multisensory stimuli remains contested. In the current study, we investigated whether diverting attention from well-known multisensory tasks would disrupt integration and whether the complexity of the stimulus and task modulated this interaction. A secondary objective of this study was to investigate individual differences in the interaction of attention and multisensory integration. Participants completed a simple audiovisual speeded detection task and McGurk task under various perceptual load conditions: no load (multisensory task while visual distractors present), low load (multisensory task while detecting the presence of a yellow letter in the visual distractors), and high load (multisensory task while detecting the presence of a number in the visual distractors). Consistent with prior studies, we found that increased perceptual load led to decreased reports of the McGurk illusion, thus confirming the necessity of attention for the integration of speech stimuli. Although increased perceptual load led to longer response times for all stimuli in the speeded detection task, participants responded faster on multisensory trials than unisensory trials. However, the increase in multisensory response times violated the race model for no and low perceptual load conditions only. Additionally, a geometric measure of Miller's inequality showed a decrease in multisensory integration for the speeded detection task with increasing perceptual load. Surprisingly, we found diverging changes in multisensory integration with increasing load for participants who did not show integration for the no load condition: no changes in integration for the McGurk task with increasing load but increases in integration for the detection task. The results of this study indicate that attention plays a crucial role in multisensory integration for both highly complex and simple multisensory tasks and that attention may interact differently with multisensory processing in individuals who do not strongly integrate multisensory information.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

PubMed

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

From systems biology to dynamical neuropharmacology: proposal for a new methodology.

PubMed

Erdi, P; Kiss, T; Tóth, J; Ujfalussy, B; Zalányi, L

2006-07-01

The concepts and methods of systems biology are extended to neuropharmacology in order to test and design drugs for the treatment of neurological and psychiatric disorders. Computational modelling by integrating compartmental neural modelling techniques and detailed kinetic descriptions of pharmacological modulation of transmitter-receptor interaction is offered as a method to test the electrophysiological and behavioural effects of putative drugs. Even more, an inverse method is suggested as a method for controlling a neural system to realise a prescribed temporal pattern. In particular, as an application of the proposed new methodology, a computational platform is offered to analyse the generation and pharmacological modulation of theta rhythm related to anxiety.

Novel graphical environment for virtual and real-world operations of tracked mobile manipulators

NASA Astrophysics Data System (ADS)

Chen, ChuXin; Trivedi, Mohan M.; Azam, Mir; Lassiter, Nils T.

1993-08-01

A simulation, animation, visualization and interactive control (SAVIC) environment has been developed for the design and operation of an integrated mobile manipulator system. This unique system possesses the abilities for (1) multi-sensor simulation, (2) kinematics and locomotion animation, (3) dynamic motion and manipulation animation, (4) transformation between real and virtual modes within the same graphics system, (5) ease in exchanging software modules and hardware devices between real and virtual world operations, and (6) interfacing with a real robotic system. This paper describes a working system and illustrates the concepts by presenting the simulation, animation and control methodologies for a unique mobile robot with articulated tracks, a manipulator, and sensory modules.

Self-starting picosecond optical pulse source using stimulated Brillouin scattering in an optical fiber.

PubMed

Tang, W W; Shu, C

2005-02-21

We demonstrate a regeneratively mode-locked optical pulse source at about 10 GHz using an optoelectronic oscillator constructed with an electro-absorption modulator integrated distributed feedback laser diode. The 10 GHz RF component is derived from the interaction between the pump wave and the backscattered, frequency-downshifted Stokes wave resulted from stimulated Brillouin scattering in an optical fiber. The component serves as a modulation source for the 1556 nm laser diode without the need for any electrical or optical RF filter to perform the frequency extraction. Dispersion-compensated fiber, dispersion-shifted fiber, and standard single-mode fiber have been used respectively to generate optical pulses at variable repetition rates.

Unconscious presentation of fearful face modulates electrophysiological responses to emotional prosody.

PubMed

Doi, Hirokazu; Shinohara, Kazuyuki

2015-03-01

Cross-modal integration of visual and auditory emotional cues is supposed to be advantageous in the accurate recognition of emotional signals. However, the neural locus of cross-modal integration between affective prosody and unconsciously presented facial expression in the neurologically intact population is still elusive at this point. The present study examined the influences of unconsciously presented facial expressions on the event-related potentials (ERPs) in emotional prosody recognition. In the experiment, fearful, happy, and neutral faces were presented without awareness by continuous flash suppression simultaneously with voices containing laughter and a fearful shout. The conventional peak analysis revealed that the ERPs were modulated interactively by emotional prosody and facial expression at multiple latency ranges, indicating that audio-visual integration of emotional signals takes place automatically without conscious awareness. In addition, the global field power during the late-latency range was larger for shout than for laughter only when a fearful face was presented unconsciously. The neural locus of this effect was localized to the left posterior fusiform gyrus, giving support to the view that the cortical region, traditionally considered to be unisensory region for visual processing, functions as the locus of audiovisual integration of emotional signals. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evaluation of an Online Program To Teach Microbiology to Internal Medicine Residents

PubMed Central

Burd, Eileen M.; Kraft, Colleen S.; Armstrong, Wendy S.; Lenorr, Kenya; Spicer, Jennifer O.; Martin, Donna; del Rio, Carlos

2014-01-01

Microbiology rounds are an integral part of infectious disease consultation service. During microbiology rounds, we highlight microbiology principles using vignettes. We created case-based, interactive, microbiology online modules similar to the vignettes presented during microbiology rounds. Since internal medicine residents rotating on our infectious disease elective have limited time to participate in rounds and learn microbiology, our objective was to evaluate the use of the microbiology online modules by internal medicine residents. We asked residents to complete 10 of 25 online modules during their infectious disease elective. We evaluated which modules they chose and the change in their knowledge level. Forty-six internal medicine residents completed assessments given before and after accessing the modules with an average of 11/20 (range, 6 to 19) and 16/20 (range, 9 to 20) correct questions, respectively (average improvement, 5 questions; P = 0.0001). The modules accessed by more than 30 residents included those related to Clostridium difficile, anaerobes, Candida spp., Streptococcus pneumoniae, influenza, Mycobacterium tuberculosis, and Neisseria meningitidis. We demonstrated improved microbiology knowledge after completion of the online modules. This improvement may not be solely attributed to completing the online modules, as fellows and faculty may have provided additional microbiology education during the rotation. PMID:25392364

Evaluation of an online program to teach microbiology to internal medicine residents.

PubMed

Guarner, Jeannette; Burd, Eileen M; Kraft, Colleen S; Armstrong, Wendy S; Lenorr, Kenya; Spicer, Jennifer O; Martin, Donna; del Rio, Carlos

2015-01-01

Microbiology rounds are an integral part of infectious disease consultation service. During microbiology rounds, we highlight microbiology principles using vignettes. We created case-based, interactive, microbiology online modules similar to the vignettes presented during microbiology rounds. Since internal medicine residents rotating on our infectious disease elective have limited time to participate in rounds and learn microbiology, our objective was to evaluate the use of the microbiology online modules by internal medicine residents. We asked residents to complete 10 of 25 online modules during their infectious disease elective. We evaluated which modules they chose and the change in their knowledge level. Forty-six internal medicine residents completed assessments given before and after accessing the modules with an average of 11/20 (range, 6 to 19) and 16/20 (range, 9 to 20) correct questions, respectively (average improvement, 5 questions; P = 0.0001). The modules accessed by more than 30 residents included those related to Clostridium difficile, anaerobes, Candida spp., Streptococcus pneumoniae, influenza, Mycobacterium tuberculosis, and Neisseria meningitidis. We demonstrated improved microbiology knowledge after completion of the online modules. This improvement may not be solely attributed to completing the online modules, as fellows and faculty may have provided additional microbiology education during the rotation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Policing Fish at Boston's Museum of Science: Studying Audiovisual Interaction in the Wild

PubMed Central

Sun, Yile; Hickey, Timothy J.; Shinn-Cunningham, Barbara; Sekuler, Robert

2015-01-01

Boston's Museum of Science supports researchers whose projects advance science and provide educational opportunities to the Museum's visitors. For our project, 60 visitors to the Museum played “Fish Police!!,” a video game that examines audiovisual integration, including the ability to ignore irrelevant sensory information. Players, who ranged in age from 6 to 82 years, made speeded responses to computer-generated fish that swam rapidly across a tablet display. Responses were to be based solely on the rate (6 or 8 Hz) at which a fish's size modulated, sinusoidally growing and shrinking. Accompanying each fish was a task-irrelevant broadband sound, amplitude modulated at either 6 or 8 Hz. The rates of visual and auditory modulation were either Congruent (both 6 Hz or 8 Hz) or Incongruent (6 and 8 or 8 and 6 Hz). Despite being instructed to ignore the sound, players of all ages responded more accurately and faster when a fish's auditory and visual signatures were Congruent. In a controlled laboratory setting, a related task produced comparable results, demonstrating the robustness of the audiovisual interaction reported here. Some suggestions are made for conducting research in public settings. PMID:27433321

Policing Fish at Boston's Museum of Science: Studying Audiovisual Interaction in the Wild.

PubMed

Goldberg, Hannah; Sun, Yile; Hickey, Timothy J; Shinn-Cunningham, Barbara; Sekuler, Robert

2015-08-01

Boston's Museum of Science supports researchers whose projects advance science and provide educational opportunities to the Museum's visitors. For our project, 60 visitors to the Museum played "Fish Police!!," a video game that examines audiovisual integration, including the ability to ignore irrelevant sensory information. Players, who ranged in age from 6 to 82 years, made speeded responses to computer-generated fish that swam rapidly across a tablet display. Responses were to be based solely on the rate (6 or 8 Hz) at which a fish's size modulated, sinusoidally growing and shrinking. Accompanying each fish was a task-irrelevant broadband sound, amplitude modulated at either 6 or 8 Hz. The rates of visual and auditory modulation were either Congruent (both 6 Hz or 8 Hz) or Incongruent (6 and 8 or 8 and 6 Hz). Despite being instructed to ignore the sound, players of all ages responded more accurately and faster when a fish's auditory and visual signatures were Congruent. In a controlled laboratory setting, a related task produced comparable results, demonstrating the robustness of the audiovisual interaction reported here. Some suggestions are made for conducting research in public settings.

Switchable Scattering Meta-Surfaces for Broadband Terahertz Modulation

PubMed Central

Unlu, M.; Hashemi, M. R.; Berry, C. W.; Li, S.; Yang, S.-H.; Jarrahi, M.

2014-01-01

Active tuning and switching of electromagnetic properties of materials is of great importance for controlling their interaction with electromagnetic waves. In spite of their great promise, previously demonstrated reconfigurable metamaterials are limited in their operation bandwidth due to their resonant nature. Here, we demonstrate a new class of meta-surfaces that exhibit electrically-induced switching in their scattering parameters at room temperature and over a broad range of frequencies. Structural configuration of the subwavelength meta-molecules determines their electromagnetic response to an incident electromagnetic radiation. By reconfiguration of the meta-molecule structure, the strength of the induced electric field and magnetic field in the opposite direction to the incident fields are varied and the scattering parameters of the meta-surface are altered, consequently. We demonstrate a custom-designed meta-surface with switchable scattering parameters at a broad range of terahertz frequencies, enabling terahertz intensity modulation with record high modulation depths and modulation bandwidths through a fully integrated, voltage-controlled device platform at room temperature. PMID:25028123

A new IPQAM modulator with high integrated degree for digital TV

NASA Astrophysics Data System (ADS)

He, Yejun; Liu, Deming; Zhu, Guangxi; Jiang, Tao; Sun, Gongxian

2008-12-01

As video on demand (VOD) services are deployed, cable operators will experience a fundamental shift in their business, moving from broadcast to unicast content delivery. Another significant change is the introduction of Gigabit Ethernet into their network, which is providing an unprecedented opportunity to turn the cable operator's infrastructure into a sustainable competitive advantage. However, Gigabit Ethernet is more than just transport; it's the foundation of the Next-Generation Digital Video Network. IPQAM modulator, which is a main equipment, aren't made in China so far. It is the first time that we did design IPQAM modulator and will apply it to interactive TV based on DWDM (dense wavelength-division multiplexing). This paper introduces the principle of IPQAM modulator and transmission approach. The differences between IPQAM and conventional QAM are analysed. Some key techniques such as scrambling, statistical multiplexing, Data over Cable Service Interface Specification (DOCSIS) 3.0, software defined radio as well as DVB simulcrypt are also studied.

Finding influential nodes for integration in brain networks using optimal percolation theory.

PubMed

Del Ferraro, Gino; Moreno, Andrea; Min, Byungjoon; Morone, Flaviano; Pérez-Ramírez, Úrsula; Pérez-Cervera, Laura; Parra, Lucas C; Holodny, Andrei; Canals, Santiago; Makse, Hernán A

2018-06-11

Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens. This result is confirmed with pharmacogenetic inactivation of the nucleus accumbens, which eliminates the formation of the memory network, while inactivations of other brain areas leave the network intact. Thus, optimal percolation theory predicts essential nodes in brain networks. This could be used to identify targets of interventions to modulate brain function.

HiRel - Reliability/availability integrated workstation tool

NASA Technical Reports Server (NTRS)

Bavuso, Salvatore J.; Dugan, Joanne B.

1992-01-01

The HiRel software tool is described and demonstrated by application to the mission avionics subsystem of the Advanced System Integration Demonstrations (ASID) system that utilizes the PAVE PILLAR approach. HiRel marks another accomplishment toward the goal of producing a totally integrated computer-aided design (CAD) workstation design capability. Since a reliability engineer generally represents a reliability model graphically before it can be solved, the use of a graphical input description language increases productivity and decreases the incidence of error. The graphical postprocessor module HARPO makes it possible for reliability engineers to quickly analyze huge amounts of reliability/availability data to observe trends due to exploratory design changes. The addition of several powerful HARP modeling engines provides the user with a reliability/availability modeling capability for a wide range of system applications all integrated under a common interactive graphical input-output capability.

Structure-Based Network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators of Structural Stability and Allosteric Interactions

PubMed Central

James, Kevin A.; Verkhivker, Gennady M.

2014-01-01

The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced “superacceptor” activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the ATP site, and may enhance allosteric cooperativity with the substrate binding region by increasing communication capabilities of mediating residues. PMID:25427151

GENETICS OF WHITE MATTER DEVELOPMENT: A DTI STUDY OF 705 TWINS AND THEIR SIBLINGS AGED 12 TO 29

PubMed Central

Chiang, Ming-Chang; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Hickie, Ian; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

2011-01-01

White matter microstructure is under strong genetic control, yet it is largely unknown how genetic influences change from childhood into adulthood. In one of the largest brain mapping studies ever performed, we determined whether the genetic control over white matter architecture depends on age, sex, socioeconomic status (SES), and intelligence quotient (IQ). We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4-Tesla), in 705 twins and their siblings (age range 12–29; 290 M/415 F). White matter integrity was quantified using a widely accepted measure, fractional anisotropy (FA). We fitted gene-environment interaction models pointwise, to visualize brain regions where age, sex, SES and IQ modulate heritability of fiber integrity. We hypothesized that environmental factors would start to outweigh genetic factors during late childhood and adolescence. Genetic influences were greater in adolescence versus adulthood, and greater in males than in females. Socioeconomic status significantly interacted with genes that affect fiber integrity: heritability was higher in those with higher SES. In people with above-average IQ, genetic factors explained over 800% of the observed FA variability in the thalamus, genu, posterior internal capsule, and superior corona radiata. In those with below-average IQ, however, only around 40% FA variability in the same regions was attributable to genetic factors. Genes affect fiber integrity, but their effects vary with age, sex, SES and IQ. Gene-environment interactions are vital to consider in the search for specific genetic polymorphisms that affect brain integrity and connectivity. PMID:20950689

Unexpected arousal modulates the influence of sensory noise on confidence

PubMed Central

Allen, Micah; Frank, Darya; Schwarzkopf, D Samuel; Fardo, Francesca; Winston, Joel S; Hauser, Tobias U; Rees, Geraint

2016-01-01

Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision. Across measures of perceptual bias, uncertainty, and physiological arousal we found that arousing disgust cues modulated the encoding of sensory noise. Furthermore, the degree to which trial-by-trial pupil fluctuations encoded this nonlinear interaction correlated with trial level confidence. Our results suggest that unexpected arousal regulates perceptual precision, such that subjective confidence reflects the integration of both external sensory and internal, embodied states. DOI: http://dx.doi.org/10.7554/eLife.18103.001 PMID:27776633

Integrated residential photovoltaic array development

NASA Astrophysics Data System (ADS)

Shepard, N. F., Jr.

1981-02-01

An optimum integrated residential photovoltaic array/module is addressed. Nineteen existing or proposed systems intended for residential applications are described. Each of these systems is rated against a comprehensive set of evaluation criteria in an effort to formulate three module design concepts for further study and analysis. This evaluation led to a number of observations which are enumerated and should be considered in future module and array designs. Three module concepts are presented as baseline design approaches to be further analyzed and optimized. These options include: (1) a rectangular, direct mounted, shingle type module; (2) an integrally mounted module with nonconductive exposed elements; and (3) an aluminum framed, stand off module. Preliminary design drawings are presented for each of these module configurations.

Integrated residential photovoltaic array development

NASA Technical Reports Server (NTRS)

Shepard, N. F., Jr.

1981-01-01

An optimum integrated residential photovoltaic array/module is addressed. Nineteen existing or proposed systems intended for residential applications are described. Each of these systems is rated against a comprehensive set of evaluation criteria in an effort to formulate three module design concepts for further study and analysis. This evaluation led to a number of observations which are enumerated and should be considered in future module and array designs. Three module concepts are presented as baseline design approaches to be further analyzed and optimized. These options include: (1) a rectangular, direct mounted, shingle type module; (2) an integrally mounted module with nonconductive exposed elements; and (3) an aluminum framed, stand off module. Preliminary design drawings are presented for each of these module configurations.

Learning collaborative teamwork: an argument for incorporating the humanities.

PubMed

Hall, Pippa; Brajtman, Susan; Weaver, Lynda; Grassau, Pamela Anne; Varpio, Lara

2014-11-01

A holistic, collaborative interprofessional team approach, which includes patients and families as significant decision-making members, has been proposed to address the increasing burden being placed on the health-care system. This project hypothesized that learning activities related to the humanities during clinical placements could enhance interprofessional teamwork. Through an interprofessional team of faculty, clinical staff, students, and patient representatives, we developed and piloted the self-learning module, "interprofessional education for collaborative person-centred practice through the humanities". The module was designed to provide learners from different professions and educational levels with a clinical placement/residency experience that would enable them, through a lens of the humanities, to better understand interprofessional collaborative person-centred care without structured interprofessional placement activities. Learners reported the self-paced and self-directed module to be a satisfactory learning experience in all four areas of care at our institution, and certain attitudes and knowledge were significantly and positively affected. The module's evaluation resulted in a revised edition providing improved structure and instruction for students with no experience in self-directed learning. The module was recently adapted into an interactive bilingual (French and English) online e-learning module to facilitate its integration into the pre-licensure curriculum at colleges and universities.

Gain Modulation in the Central Nervous System: Where Behavior, Neurophysiology, and Computation Meet

PubMed Central

SALINAS, EMILIO; SEJNOWSKI, TERRENCE J.

2010-01-01

Gain modulation is a nonlinear way in which neurons combine information from two (or more) sources, which may be of sensory, motor, or cognitive origin. Gain modulation is revealed when one input, the modulatory one, affects the gain or the sensitivity of the neuron to the other input, without modifying its selectivity or receptive field properties. This type of modulatory interaction is important for two reasons. First, it is an extremely widespread integration mechanism; it is found in a plethora of cortical areas and in some subcortical structures as well, and as a consequence it seems to play an important role in a striking variety of functions, including eye and limb movements, navigation, spatial perception, attentional processing, and object recognition. Second, there is a theoretical foundation indicating that gain-modulated neurons may serve as a basis for a general class of computations, namely, coordinate transformations and the generation of invariant responses, which indeed may underlie all the brain functions just mentioned. This article describes the relationships between computational models, the physiological properties of a variety of gain-modulated neurons, and some of the behavioral consequences of damage to gain-modulated neural representations. PMID:11597102

Integration of hybrid silicon lasers and electroabsorption modulators.

PubMed

Sysak, Matthew N; Anthes, Joel O; Bowers, John E; Raday, Omri; Jones, Richard

2008-08-18

We present an integration platform based on quantum well intermixing for multi-section hybrid silicon lasers and electroabsorption modulators. As a demonstration of the technology, we have fabricated discrete sampled grating DBR lasers and sampled grating DBR lasers integrated with InGaAsP/InP electroabsorption modulators. The integrated sampled grating DBR laser-modulators use the as-grown III-V bandgap for optical gain, a 50 nm blue shifted bandgap for the electrabosprtion modulators, and an 80 nm blue shifted bandgap for low loss mirrors. Laser continuous wave operation up to 45 ?C is achieved with output power >1.0 mW and threshold current of <50 mA. The modulator bandwidth is >2GHz with 5 dB DC extinction.

MISPS: Module integrated solar position sensor for concentration photovoltaics

NASA Astrophysics Data System (ADS)

Pardell, Ricard

2012-10-01

This paper describes a new device, the MISPS (Module Integrated. Solar Position Sensor) for CPV systems. Its main innovation lies in it being module integrated, so that the sensor is a constituent part of the module and uses its optics. The MISPS has been designed within the scope of the CPVRS project, but it can be used in any refractive optics CPV system.

Unveiling network-based functional features through integration of gene expression into protein networks.

PubMed

Jalili, Mahdi; Gebhardt, Tom; Wolkenhauer, Olaf; Salehzadeh-Yazdi, Ali

2018-06-01

Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might not be adequate to capture the complexity of phenotypes. Therefore, integrated multi-omics approaches have been used to unravel genotype-phenotype relationships such as global regulatory mechanisms and complex metabolic networks in different eukaryotic organisms. Some of the progress and challenges associated with integrated omics studies have been reviewed previously in comprehensive studies. In this work, we highlight and review the progress, challenges and advantages associated with emerging approaches, integrating gene expression and protein-protein interaction networks to unravel network-based functional features. This includes identifying disease related genes, gene prioritization, clustering protein interactions, developing the modules, extract active subnetworks and static protein complexes or dynamic/temporal protein complexes. We also discuss how these approaches contribute to our understanding of the biology of complex traits and diseases. This article is part of a Special Issue entitled: Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers. Copyright © 2018 Elsevier B.V. All rights reserved.

Active material, optical mode and cavity impact on nanoscale electro-optic modulation performance

NASA Astrophysics Data System (ADS)

Amin, Rubab; Suer, Can; Ma, Zhizhen; Sarpkaya, Ibrahim; Khurgin, Jacob B.; Agarwal, Ritesh; Sorger, Volker J.

2017-10-01

Electro-optic modulation is a key function in optical data communication and possible future optical compute engines. The performance of modulators intricately depends on the interaction between the actively modulated material and the propagating waveguide mode. While a variety of high-performance modulators have been demonstrated, no comprehensive picture of what factors are most responsible for high performance has emerged so far. Here we report the first systematic and comprehensive analytical and computational investigation for high-performance compact on-chip electro-optic modulators by considering emerging active materials, model considerations and cavity feedback at the nanoscale. We discover that the delicate interplay between the material characteristics and the optical mode properties plays a key role in defining the modulator performance. Based on physical tradeoffs between index modulation, loss, optical confinement factors and slow-light effects, we find that there exist combinations of bias, material and optical mode that yield efficient phase or amplitude modulation with acceptable insertion loss. Furthermore, we show how material properties in the epsilon near zero regime enable reduction of length by as much as by 15 times. Lastly, we introduce and apply a cavity-based electro-optic modulator figure of merit, Δλ/Δα, relating obtainable resonance tuning via phase shifting relative to the incurred losses due to the fundamental Kramers-Kronig relations suggesting optimized device operating regions with optimized modulation-to-loss tradeoffs. This work paves the way for a holistic design rule of electro-optic modulators for high-density on-chip integration.

An agent-based hydroeconomic model to evaluate water policies in Jordan

NASA Astrophysics Data System (ADS)

Yoon, J.; Gorelick, S.

2014-12-01

Modern water systems can be characterized by a complex network of institutional and private actors that represent competing sectors and interests. Identifying solutions to enhance water security in such systems calls for analysis that can adequately account for this level of complexity and interaction. Our work focuses on the development of a hierarchical, multi-agent, hydroeconomic model that attempts to realistically represent complex interactions between hydrologic and multi-faceted human systems. The model is applied to Jordan, one of the most water-poor countries in the world. In recent years, the water crisis in Jordan has escalated due to an ongoing drought and influx of refugees from regional conflicts. We adopt a modular approach in which biophysical modules simulate natural and engineering phenomena, and human modules represent behavior at multiple scales of decision making. The human modules employ agent-based modeling, in which agents act as autonomous decision makers at the transboundary, state, organizational, and user levels. A systematic nomenclature and conceptual framework is used to characterize model agents and modules. Concepts from the Unified Modeling Language (UML) are adopted to promote clear conceptualization of model classes and process sequencing, establishing a foundation for full deployment of the integrated model in a scalable object-oriented programming environment. Although the framework is applied to the Jordanian water context, it is generalizable to other regional human-natural freshwater supply systems.

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

PubMed Central

Valentine, Cathleen D.; Haggie, Peter M.

2011-01-01

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

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

PubMed

Valentine, Cathleen D; Haggie, Peter M

2011-08-15

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

The Education and Public Engagement (EPE) Component of the Ocean Observatories Initiative (OOI): Enabling Near Real-Time Data Use in Undergraduate Classrooms

NASA Astrophysics Data System (ADS)

Glenn, S. M.; Companion, C.; Crowley, M.; deCharon, A.; Fundis, A. T.; Kilb, D. L.; Levenson, S.; Lichtenwalner, C. S.; McCurdy, A.; McDonnell, J. D.; Overoye, D.; Risien, C. M.; Rude, A.; Wieclawek, J., III

2011-12-01

The National Science Foundation's Ocean Observatories Initiative (OOI) is constructing observational and computer infrastructure that will provide sustained ocean measurements to study climate variability, ocean circulation, ecosystem dynamics, air-sea exchange, seafloor processes, and plate-scale geodynamics over the next ~25-30 years. To accomplish this, the Consortium for Ocean Leadership established four Implementing Organizations: (1) Regional Scale Nodes; (2) Coastal and Global Scale Nodes; (3) Cyberinfrastructure (CI); and (4) Education and Public Engagement (EPE). The EPE, which we represent, was just recently established to provide a new layer of cyber-interactivity for educators to bring near real-time data, images and videos of our Earth's oceans into their learning environments. Our focus over the next four years is engaging educators of undergraduates and free-choice learners. Demonstration projects of the OOI capabilities will use an Integrated Education Toolkit to access OOI data through the Cyberinfrastructure's On Demand Measurement Processing capability. We will present our plans to develop six education infrastructure software modules: Education Web Services (middleware), Visualization Tools, Concept Map and Lab/Lesson Builders, Collaboration Tools, and an Education Resources Database. The software release of these tools is staggered to coincide with other major OOI releases. The first release will include stand-alone versions of the first four EPE modules (Fall 2012). Next, all six EPE modules will be integrated within the OOI cyber-framework (Fall 2013). The last release will include advanced capabilities for all six modules within a collaborative network that leverages the CI's Integrated Observatory Network (Fall 2014). We are looking for undergraduate and informal science educators to provide feedback and guidance on the project, please contact us if you are interested in partnering with us.

Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

PubMed Central

Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

2013-01-01

Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

Carboxysomes: metabolic modules for CO 2 fixation

DOE PAGES

Turmo, Aiko; Gonzalez-Esquer, Cesar Raul; Kerfeld, Cheryl A.

2017-08-14

The carboxysome is a bacterial microcompartment encapsulating the enzymes carbonic anhydrase and ribulose-1,5-bisphosphate carboxylase/oxygenase. As the site of CO 2 fixation, it serves an essential role in the carbon dioxide concentrating mechanism of many chemoautotrophs and all cyanobacteria. Carboxysomes and other bacterial microcompartments self-assemble through specific protein–protein interactions that are typically mediated by conserved protein domains. In this review, we frame our current understanding of carboxysomes in the context of their component protein domains with their inherent function as the ‘building blocks’ of carboxysomes. These building blocks are organized in genetic modules (conserved chromosomal loci) that encode for carboxysomes andmore » ancillary proteins essential for the integration of the organelle with the rest of cellular metabolism. This conceptual framework provides the foundation for ‘plug-and-play’ engineering of carboxysomes as CO 2 fixation modules in a variety of biotechnological applications.« less

Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments

NASA Astrophysics Data System (ADS)

Stornaiuolo, Mariano; Bruno, Agostino; Botta, Lorenzo; Regina, Giuseppe La; Cosconati, Sandro; Silvestri, Romano; Marinelli, Luciana; Novellino, Ettore

2015-10-01

A Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.

Interactions between attention, context and learning in primary visual cortex.

PubMed

Gilbert, C; Ito, M; Kapadia, M; Westheimer, G

2000-01-01

Attention in early visual processing engages the higher order, context dependent properties of neurons. Even at the earliest stages of visual cortical processing neurons play a role in intermediate level vision - contour integration and surface segmentation. The contextual influences mediating this process may be derived from long range connections within primary visual cortex (V1). These influences are subject to perceptual learning, and are strongly modulated by visuospatial attention, which is itself a learning dependent process. The attentional influences may involve interactions between feedback and horizontal connections in V1. V1 is therefore a dynamic and active processor, subject to top-down influences.

Scaling vectors of attoJoule per bit modulators

NASA Astrophysics Data System (ADS)

Sorger, Volker J.; Amin, Rubab; Khurgin, Jacob B.; Ma, Zhizhen; Dalir, Hamed; Khan, Sikandar

2018-01-01

Electro-optic modulation performs the conversion between the electrical and optical domain with applications in data communication for optical interconnects, but also for novel optical computing algorithms such as providing nonlinearity at the output stage of optical perceptrons in neuromorphic analog optical computing. While resembling an optical transistor, the weak light-matter-interaction makes modulators 105 times larger compared to their electronic counterparts. Since the clock frequency for photonics on-chip has a power-overhead sweet-spot around tens of GHz, ultrafast modulation may only be required in long-distance communication, not for short on-chip links. Hence, the search is open for power-efficient on-chip modulators beyond the solutions offered by foundries to date. Here, we show scaling vectors towards atto-Joule per bit efficient modulators on-chip as well as some experimental demonstrations of novel plasmonic modulators with sub-fJ/bit efficiencies. Our parametric study of placing different actively modulated materials into plasmonic versus photonic optical modes shows that 2D materials overcompensate their miniscule modal overlap by their unity-high index change. Furthermore, we reveal that the metal used in plasmonic-based modulators not only serves as an electrical contact, but also enables low electrical series resistances leading to near-ideal capacitors. We then discuss the first experimental demonstration of a photon-plasmon-hybrid graphene-based electro-absorption modulator on silicon. The device shows a sub-1 V steep switching enabled by near-ideal electrostatics delivering a high 0.05 dB V-1 μm-1 performance requiring only 110 aJ/bit. Improving on this demonstration, we discuss a plasmonic slot-based graphene modulator design, where the polarization of the plasmonic mode aligns with graphene’s in-plane dimension; where a push-pull dual-gating scheme enables 2 dB V-1 μm-1 efficient modulation allowing the device to be just 770 nm short for 3 dB small signal modulation. Lastly, comparing the switching energy of transistors to modulators shows that modulators based on emerging materials and plasmonic-silicon hybrid integration perform on-par relative to their electronic counter parts. This in turn allows for a device-enabled two orders-of-magnitude improvement of electrical-optical co-integrated network-on-chips over electronic-only architectures. The latter opens technological opportunities in cognitive computing, dynamic data-driven applications systems, and optical analog computer engines including neuromorphic photonic computing.

[Propranolol beta-blocker decrease in the concentration of high-affinity binding sites for calcium ions by sarcolemma membranes of the rat heart].

PubMed

Seleznev, Iu M; Martynov, A V; Smirnov, V N

1982-05-01

In vivo administration of propranolol considerably inhibits the isoproterenol-stimulated increase in 45Ca accumulation by the myocardium and completely eliminates the potentiation of isoproterenol effect by hydrocortisone. A significant lowering of the concentration of high affinity binding sites for calcium in the sarcolemmal membranes can be produced by propranolol in vitro. Under these conditions, the glucocorticoids do not change the sarcolemmal Ca2+-binding parameters or modulate the propranolol effect. Therefore, for the manifestation of glucocorticoid action to be brought about, the integrity of the cells is apparently required, while propranolol seems to change calcium binding by direct interaction with the sarcolemmal membranes. It is suggested that in vivo propranolol inhibition of catecholamine effect on calcium ion accumulation by the myocardium depends on the interaction with the beta-receptors and direct modulation of the concentration of high affinity binding sites for calcium ions on the surface of the sarcolemma.

imDEV: a graphical user interface to R multivariate analysis tools in Microsoft Excel

PubMed Central

Grapov, Dmitry; Newman, John W.

2012-01-01

Summary: Interactive modules for Data Exploration and Visualization (imDEV) is a Microsoft Excel spreadsheet embedded application providing an integrated environment for the analysis of omics data through a user-friendly interface. Individual modules enables interactive and dynamic analyses of large data by interfacing R's multivariate statistics and highly customizable visualizations with the spreadsheet environment, aiding robust inferences and generating information-rich data visualizations. This tool provides access to multiple comparisons with false discovery correction, hierarchical clustering, principal and independent component analyses, partial least squares regression and discriminant analysis, through an intuitive interface for creating high-quality two- and a three-dimensional visualizations including scatter plot matrices, distribution plots, dendrograms, heat maps, biplots, trellis biplots and correlation networks. Availability and implementation: Freely available for download at http://sourceforge.net/projects/imdev/. Implemented in R and VBA and supported by Microsoft Excel (2003, 2007 and 2010). Contact: John.Newman@ars.usda.gov Supplementary Information: Installation instructions, tutorials and users manual are available at http://sourceforge.net/projects/imdev/. PMID:22815358

Modulational instability, beak-shaped rogue waves, multi-dark-dark solitons and dynamics in pair-transition-coupled nonlinear Schrödinger equations.

PubMed

Zhang, Guoqiang; Yan, Zhenya; Wen, Xiao-Yong

2017-07-01

The integrable coupled nonlinear Schrödinger equations with four-wave mixing are investigated. We first explore the conditions for modulational instability of continuous waves of this system. Secondly, based on the generalized N -fold Darboux transformation (DT), beak-shaped higher-order rogue waves (RWs) and beak-shaped higher-order rogue wave pairs are derived for the coupled model with attractive interaction in terms of simple determinants. Moreover, we derive the simple multi-dark-dark and kink-shaped multi-dark-dark solitons for the coupled model with repulsive interaction through the generalizing DT. We explore their dynamics and classifications by different kinds of spatial-temporal distribution structures including triangular, pentagonal, 'claw-like' and heptagonal patterns. Finally, we perform the numerical simulations to predict that some dark solitons and RWs are stable enough to develop within a short time. The results would enrich our understanding on nonlinear excitations in many coupled nonlinear wave systems with transition coupling effects.

Orexin A/Hypocretin Modulates Leptin Receptor-Mediated Signaling by Allosteric Modulations Mediated by the Ghrelin GHS-R1A Receptor in Hypothalamic Neurons.

PubMed

Medrano, Mireia; Aguinaga, David; Reyes-Resina, Irene; Canela, Enric I; Mallol, Josefa; Navarro, Gemma; Franco, Rafael

2018-06-01

The hypothalamus is a key integrator of nutrient-seeking signals in the form of hormones and metabolites originated in both the central nervous system and the periphery. The main autocrine and paracrine target of orexinergic-related hormones such as leptin, orexin/hypocretin, and ghrelin are neuropeptide Y neurons located in the arcuate nucleus of the hypothalamus. The aim of this study was to investigate the expression and the molecular and functional relationships between leptin, orexin/hypocretin and ghrelin receptors. Biophysical studies in a heterologous system showed physical interactions between them, with potential formation of heterotrimeric complexes. Functional assays showed robust allosteric interactions particularly different when the three receptors are expressed together. Further biochemical and pharmacological assays provided evidence of heterotrimer functional expression in primary cultures of hypothalamic neurons. These findings constitute evidence of close relationships in the action of the three hormones already starting at the receptor level in hypothalamic cells.

Reward modulates the effect of visual cortical microstimulation on perceptual decisions

PubMed Central

Cicmil, Nela; Cumming, Bruce G; Parker, Andrew J; Krug, Kristine

2015-01-01

Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices. However, it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur. We combined electrical microstimulation of functionally specific groups of neurons in visual area V5/MT with performance-contingent reward manipulation, while monkeys performed a visual discrimination task. Microstimulation was less effective in shifting perceptual choices towards the stimulus preferences of the stimulated neurons when available reward was larger. Psychophysical control experiments showed this result was not explained by a selective change in response strategy on microstimulated trials. A bounded accumulation decision model, applied to analyse behavioural performance, revealed that the interaction of expected reward with microstimulation can be explained if expected reward modulates a sensory representation stage of perceptual decision-making, in addition to the better-known effects at the integration stage. DOI: http://dx.doi.org/10.7554/eLife.07832.001 PMID:26402458

Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

PubMed Central

König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

2008-01-01

Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

Protein conformational modulation by photons: a mechanism for laser treatment effects.

PubMed

Liebert, Ann D; Bicknell, Brian T; Adams, Roger D

2014-03-01

Responsiveness to low-level laser treatment (LLTT) at a wavelength of 450-910 nm has established it as an effective treatment of medical, veterinary and dental chronic pain, chronic inflammation conditions (arthritis and macular degeneration), wound repair, and lymphoedema, yet the mechanisms underlying the effectiveness of LLLT remain unclear. However, there is now sufficient evidence from recent research to propose an integrated model of LLLT action. The hypothesis presented in this paper is that external applications of photons (through laser at an appropriate dose) modulates the nervous system through an integrated mechanism. This stimulated mechanism involves protein-to-protein interaction, where two or more proteins bind together to facilitate molecular processes, including modification of proteins by members of SUMO (small ubiquitin-related modifier proteins) and also protein phosphorylation and tyrosination. SUMO has been shown to have a role in multiple nuclear and perinuclear targets, including ion channels, and in the maintenance of telomeres and the post-translational modification of genes. The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots.

A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies.

PubMed

Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne

2014-01-01

Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots. PMID:22563474

Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data.

PubMed

Farber, Charles R

2010-11-01

Bone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system-related gene ontology (GO) category "response to virus" (p = 7.6 × 10(-11)). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD. © 2010 American Society for Bone and Mineral Research.

Co-expression network with protein-protein interaction and transcription regulation in malaria parasite Plasmodium falciparum.

PubMed

Yu, Fu-Dong; Yang, Shao-You; Li, Yuan-Yuan; Hu, Wei

2013-04-10

Malaria continues to be one of the most severe global infectious diseases, as a major threat to human health and economic development. Network-based biological analysis is a promising approach to uncover key genes and biological processes from a network viewpoint, which could not be recognized from individual gene-based signatures. We integrated gene co-expression profile with protein-protein interaction and transcriptional regulation information to construct a comprehensive gene co-expression network of Plasmodium falciparum. Based on this network, we identified 10 core modules by using ICE (Iterative Clique Enumeration) algorithm, which were essential for malaria parasite development in intraerythrocytic developmental cycle (IDC) stages. In each module, all genes were highly correlated probably due to co-regulation or formation of a protein complex. Some of these genes were recognized to be differentially coexpressed among three close-by IDC stages. The gene of prpf8 (PFD0265w) encoding pre-mRNA processing splicing factor 8 product was identified as DCGs (differentially co-expressed genes) among IDC stages, although this gene function was seldom reported in previous researches. Integrating the species-specific gene prediction and differential co-expression gene detection, we found some modules could perform species-specific functions according to some of genes in these modules were species-specific genes, like the module 10. Furthermore, in order to reveal the underlying mechanisms of the erythrocyte invasion by P. falciparum, Steiner Tree algorithm was employed to identify the invasion subnetwork from our gene co-expression network. The subnetwork-based analysis indicated that some important Plasmodium parasite specific genes could corporate with each other and be co-regulated during the parasite invasion process, which including a head-to-head gene pair of PfRH2a (PF13_0198) and PfRH2b (MAL13P1.176). This study based on gene co-expression network could shed new insights on the mechanisms of pathogenesis, even virulence and P. falciparum development. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Optical integration of SPO mirror modules in the ATHENA telescope

NASA Astrophysics Data System (ADS)

Valsecchi, G.; Marioni, F.; Bianucci, G.; Zocchi, F. E.; Gallieni, D.; Parodi, G.; Ottolini, M.; Collon, M.; Civitani, M.; Pareschi, G.; Spiga, D.; Bavdaz, M.; Wille, E.

2017-08-01

ATHENA (Advanced Telescope for High-ENergy Astrophysics) is the next high-energy astrophysical mission selected by the European Space Agency for launch in 2028. The X-ray telescope consists of 1062 silicon pore optics mirror modules with a target angular resolution of 5 arcsec. Each module must be integrated on a 3 m structure with an accuracy of 1.5 arcsec for alignment and assembly. This industrial and scientific team is developing the alignment and integration process of the SPO mirror modules based on ultra-violet imaging at the 12 m focal plane. This technique promises to meet the accuracy requirement while, at the same time, allowing arbitrary integration sequence and mirror module exchangeability. Moreover, it enables monitoring the telescope point spread function during the planned 3-year integration phase.

A W-band integrated power module using MMIC MESFET power amplifiers and varactor doublers

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

Ho, T.C.; Chen, Seng Woon; Pande, K.

1993-12-01

A high-performance integrated power module using U-band MMIC MESFET power amplifiers in conjunction with W-band MMIC high efficiency varactor doublers has been developed for millimeter-wave system applications. This paper presents the design, fabrication, and performance of this W-band integrated power module. Measured results of the complete integrated power module show an output power of 90 mW with an overall associated gain of 29.5 dB at 94 GHz. A saturated power of over 95 mW was also achieved. These results represent the highest reported power and gain at W-band using MESFET and varactor frequency doubling technologies. This integrated power module ismore » suitable for the future 94 GHz missile seeker applications.« less

A network analysis of cofactor-protein interactions for analyzing associations between human nutrition and diseases

PubMed Central

Scott-Boyer, Marie Pier; Lacroix, Sébastien; Scotti, Marco; Morine, Melissa J.; Kaput, Jim; Priami, Corrado

2016-01-01

The involvement of vitamins and other micronutrients in intermediary metabolism was elucidated in the mid 1900’s at the level of individual biochemical reactions. Biochemical pathways remain the foundational knowledgebase for understanding how micronutrient adequacy modulates health in all life stages. Current daily recommended intakes were usually established on the basis of the association of a single nutrient to a single, most sensitive adverse effect and thus neglect interdependent and pleiotropic effects of micronutrients on biological systems. Hence, the understanding of the impact of overt or sub-clinical nutrient deficiencies on biological processes remains incomplete. Developing a more complete view of the role of micronutrients and their metabolic products in protein-mediated reactions is of importance. We thus integrated and represented cofactor-protein interaction data from multiple and diverse sources into a multi-layer network representation that links cofactors, cofactor-interacting proteins, biological processes, and diseases. Network representation of this information is a key feature of the present analysis and enables the integration of data from individual biochemical reactions and protein-protein interactions into a systems view, which may guide strategies for targeted nutritional interventions aimed at improving health and preventing diseases. PMID:26777674

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

Kapusta, P.; Kisielewski, B.

In this paper the overvoltage protection modules (OVP) for the power supply (PS) system of the Belle II pixel detector (PXD) are described. The aim of the OVP is to protect the detector and associated electronics against overvoltage conditions. Most critical in the system are voltages supplying the front-end ASICs. The PXD detector consists of the DEPFET sensor modules with integrated chips like the Drain Current Digitizer, the Switcher and the Data Handling Processor. These chips, implemented in modern sub-micron technologies, are quite vulnerable to variations in the supply voltages. The PXD will be placed in the Belle II experimentmore » as close as possible to the interaction point, where access during experiment is very limited or even impossible, thus the PS and OVP systems exploit the remote-sensing method. Overvoltage conditions are due to failures of the PS itself, wrong setting of the output voltages or transient voltages coming out of hard noisy environment of the experiment. The OVP modules are parts of the PS modules. For powering the PXD 40 PS modules are placed 15 m outside the Belle II spectrometer. Each one is equipped with the OVP board. All voltages (22) are grouped in 4 domains: Analog, Digital, Steering and Gate which have independent grounds. The OVP boards are designed from integrated circuits from Linear Technology. All configurations were simulated with the Spice program. The control electronics is designed in a Xilinx CPLD. Two types of integrated circuits were used. LT4356 surge stopper protects loads from high voltage transients. The output voltages are limited to a safe value and also protect loads against over current faults. For less critical voltages, the LTC2912 voltage monitors are used that detect under-voltage and overvoltage events. It has to be noted that the OVP system is working independently of any other protection of the PS system, which increases its overall reliability. (authors)« less

The redox-sensitive module of cyclophilin 20-3, 2-cysteine peroxiredoxin and cysteine synthase integrates sulfur metabolism and oxylipin signaling in the high light acclimation response.

PubMed

Müller, Sara M; Wang, Shanshan; Telman, Wilena; Liebthal, Michael; Schnitzer, Helena; Viehhauser, Andrea; Sticht, Carsten; Delatorre, Carolina; Wirtz, Markus; Hell, Rüdiger; Dietz, Karl-Josef

2017-09-01

The integration of redox- and reactive oxygen species-dependent signaling and metabolic activities is fundamental to plant acclimation to biotic and abiotic stresses. Previous data suggest the existence of a dynamically interacting module in the chloroplast stroma consisting of cyclophilin 20-3 (Cyp20-3), O-acetylserine(thiol)lyase B (OASTL-B), 2-cysteine peroxiredoxins A/B (2-CysPrx) and serine acetyltransferase 2;1 (SERAT2;1). The functionality of this COPS module is influenced by redox stimuli and oxophytodienoic acid (OPDA), which is the precursor for jasmonic acid. The concept of an integrating function of these proteins in stress signaling was challenged by combining transcriptome and biochemical analyses in Arabidopsis mutants devoid of oastlB, serat2;1, cyp20-3 and 2-cysprxA/B, and wild-type (WT). Leaf transcriptomes were analyzed 6 h after transfer to light intensity 10-fold in excess of growth light or under growth light. The survey of KEGG-based gene ontology groups showed common upregulation of translation- and protein homeostasis-associated transcripts under control conditions in all mutants compared with WT. The results revealed that the interference of the module was accompanied with disturbance of carbohydrate, sulfur and nitrogen metabolism, and also citric acid cycle intermediates. Apart from common regulation, specific responses at the transcriptome and metabolite level linked Cyp20-3 to cell wall-bound carbohydrates and oxylipin signaling, and 2-CysPrx to photosynthesis, sugar and amino acid metabolism. Deletion of either OASTL-B or SERAT2;1 frequently induced antagonistic changes in biochemical or molecular features. Enhanced sensitivity of mutant seedlings to OPDA and leaf discs to NaHS-administration confirmed the presumed functional interference of the COPS module in redox and oxylipin signaling. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Single Plant Root System Modeling under Soil Moisture Variation

NASA Astrophysics Data System (ADS)

Yabusaki, S.; Fang, Y.; Chen, X.; Scheibe, T. D.

2016-12-01

A prognostic Virtual Plant-Atmosphere-Soil System (vPASS) model is being developed that integrates comprehensively detailed mechanistic single plant modeling with microbial, atmospheric, and soil system processes in its immediate environment. Three broad areas of process module development are targeted: Incorporating models for root growth and function, rhizosphere interactions with bacteria and other organisms, litter decomposition and soil respiration into established porous media flow and reactive transport models Incorporating root/shoot transport, growth, photosynthesis and carbon allocation process models into an integrated plant physiology model Incorporating transpiration, Volatile Organic Compounds (VOC) emission, particulate deposition and local atmospheric processes into a coupled plant/atmosphere model. The integrated plant ecosystem simulation capability is being developed as open source process modules and associated interfaces under a modeling framework. The initial focus addresses the coupling of root growth, vascular transport system, and soil under drought scenarios. Two types of root water uptake modeling approaches are tested: continuous root distribution and constitutive root system architecture. The continuous root distribution models are based on spatially averaged root development process parameters, which are relatively straightforward to accommodate in the continuum soil flow and reactive transport module. Conversely, the constitutive root system architecture models use root growth rates, root growth direction, and root branching to evolve explicit root geometries. The branching topologies require more complex data structures and additional input parameters. Preliminary results are presented for root model development and the vascular response to temporal and spatial variations in soil conditions.

Semantics based approach for analyzing disease-target associations.

PubMed

Kaalia, Rama; Ghosh, Indira

2016-08-01

A complex disease is caused by heterogeneous biological interactions between genes and their products along with the influence of environmental factors. There have been many attempts for understanding the cause of these diseases using experimental, statistical and computational methods. In the present work the objective is to address the challenge of representation and integration of information from heterogeneous biomedical aspects of a complex disease using semantics based approach. Semantic web technology is used to design Disease Association Ontology (DAO-db) for representation and integration of disease associated information with diabetes as the case study. The functional associations of disease genes are integrated using RDF graphs of DAO-db. Three semantic web based scoring algorithms (PageRank, HITS (Hyperlink Induced Topic Search) and HITS with semantic weights) are used to score the gene nodes on the basis of their functional interactions in the graph. Disease Association Ontology for Diabetes (DAO-db) provides a standard ontology-driven platform for describing genes, proteins, pathways involved in diabetes and for integrating functional associations from various interaction levels (gene-disease, gene-pathway, gene-function, gene-cellular component and protein-protein interactions). An automatic instance loader module is also developed in present work that helps in adding instances to DAO-db on a large scale. Our ontology provides a framework for querying and analyzing the disease associated information in the form of RDF graphs. The above developed methodology is used to predict novel potential targets involved in diabetes disease from the long list of loose (statistically associated) gene-disease associations. Copyright © 2016 Elsevier Inc. All rights reserved.

An integrated platform for biomolecule interaction analysis

NASA Astrophysics Data System (ADS)

Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

2013-02-01

We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains.

PubMed

Rungaldier, Stefanie; Oberwagner, Walter; Salzer, Ulrich; Csaszar, Edina; Prohaska, Rainer

2013-03-01

The widely expressed, homo-oligomeric, lipid raft-associated, monotopic integral membrane protein stomatin and its homologues are known to interact with and modulate various ion channels and transporters. Stomatin is a major protein of the human erythrocyte membrane, where it associates with and modifies the glucose transporter GLUT1; however, previous attempts to purify hetero-oligomeric stomatin complexes for biochemical analysis have failed. Because lateral interactions of membrane proteins may be short-lived and unstable, we have used in situ chemical cross-linking of erythrocyte membranes to fix the stomatin complexes for subsequent purification by immunoaffinity chromatography. To further enrich stomatin, we prepared detergent-resistant membranes either before or after cross-linking. Mass spectrometry of the isolated, high molecular, cross-linked stomatin complexes revealed the major interaction partners as glucose transporter-1 (GLUT1), anion exchanger (band 3), and water channel (aquaporin-1). Moreover, ferroportin-1 (SLC40A1), urea transporter-1 (SLC14A1), nucleoside transporter (SLC29A1), the calcium-pump (Ca-ATPase-4), CD47, and flotillins were identified as stomatin-interacting proteins. These findings are in line with the hypothesis that stomatin plays a role as membrane-bound scaffolding protein modulating transport proteins. Copyright © 2012 Elsevier B.V. All rights reserved.

Augmenting reality in Direct View Optical (DVO) overlay applications

NASA Astrophysics Data System (ADS)

Hogan, Tim; Edwards, Tim

2014-06-01

The integration of overlay displays into rifle scopes can transform precision Direct View Optical (DVO) sights into intelligent interactive fire-control systems. Overlay displays can provide ballistic solutions within the sight for dramatically improved targeting, can fuse sensor video to extend targeting into nighttime or dirty battlefield conditions, and can overlay complex situational awareness information over the real-world scene. High brightness overlay solutions for dismounted soldier applications have previously been hindered by excessive power consumption, weight and bulk making them unsuitable for man-portable, battery powered applications. This paper describes the advancements and capabilities of a high brightness, ultra-low power text and graphics overlay display module developed specifically for integration into DVO weapon sight applications. Central to the overlay display module was the development of a new general purpose low power graphics controller and dual-path display driver electronics. The graphics controller interface is a simple 2-wire RS-232 serial interface compatible with existing weapon systems such as the IBEAM ballistic computer and the RULR and STORM laser rangefinders (LRF). The module features include multiple graphics layers, user configurable fonts and icons, and parameterized vector rendering, making it suitable for general purpose DVO overlay applications. The module is configured for graphics-only operation for daytime use and overlays graphics with video for nighttime applications. The miniature footprint and ultra-low power consumption of the module enables a new generation of intelligent DVO systems and has been implemented for resolutions from VGA to SXGA, in monochrome and color, and in graphics applications with and without sensor video.

Asthma in the community: Designing instruction to help students explore scientific dilemmas that impact their lives

NASA Astrophysics Data System (ADS)

Tate, Erika Dawn

School science instruction that connects to students' diverse home, cultural, or linguistic experiences can encourage lifelong participation in the scientific dilemmas that impact students' lives. This dissertation seeks effective ways to support high school students as they learn complex science topics and use their knowledge to transform their personal and community environments. Applying the knowledge integration perspective, I collaborated with education, science, and community partners to design a technology enhanced science module, Improving Your Community's Asthma Problem. This exemplar community science curriculum afforded students the opportunity to (a) investigate a local community health issue, (b) interact with relevant evidence related to physiology, clinical management, and environmental risks, and (c) construct an integrated understanding of the asthma problem in their community. To identify effective instructional scaffolds that engage students in the knowledge integration process and prepare them to participate in community science, I conducted 2 years of research that included 5 schools, 10 teachers, and over 500 students. This dissertation reports on four studies that analyzed student responses on pre-, post-, and embedded assessments. Researching across four design stages, the iterative design study investigated how to best embed the visualizations of the physiological processes breathing, asthma attack, and the allergic immune response in an inquiry activity and informed evidence-based revisions to the module. The evaluation study investigated the impact of this revised Asthma module across multiple classrooms and differences in students' prior knowledge. Combining evidence of student learning from the iterative and evaluation studies with classroom observations and teacher interviews, the longitudinal study explored the impact of teacher practices on student learning in years 1 and 2. In the final chapter, I studied how the Asthma module and students' local community influenced students as they integrated their ideas related to perspectives, evidence use, the consideration of tradeoffs, and localization to construct explanations and decision justifications regarding their community's asthma problem. In the end, this dissertation offers evidence that informs the future design of community science instruction that successfully engages students in the knowledge integration process and has implications for creating multiple opportunities for students to meaningfully participate in community science.

The ER Contact Proteins VAPA/B Interact with Multiple Autophagy Proteins to Modulate Autophagosome Biogenesis.

PubMed

Zhao, Yan G; Liu, Nan; Miao, Guangyan; Chen, Yong; Zhao, Hongyu; Zhang, Hong

2018-04-23

The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation. Depletion of VAPs impairs progression of IMs into autophagosomes. Upon autophagy induction, VAPs are recruited to autophagosome formation sites on the ER, a process mediated by their interactions with FIP200 and PI(3)P. VAPs directly interact with FIP200 and ULK1 through their conserved FFAT motifs and stabilize the ULK1/FIP200 complex at the autophagosome formation sites on the ER. The formation of ULK1 puncta is significantly reduced by VAPA/B depletion. VAPs also interact with WIPI2 and enhance the formation of the WIPI2/FIP200 ER/IM tethering complex. Depletion of VMP1, which increases the ER/IM contact, greatly elevates the interaction of VAPs with these autophagy proteins. The VAPB P56S mutation, which is associated with amyotrophic lateral sclerosis, reduces the ULK1/FIP200 interaction and impairs autophagy at an early step, similar to the effect seen in VAPA/B-depleted cells. Our study reveals that VAPs directly interact with multiple ATG proteins, thereby contributing to ER/IM contact formation for autophagosome biogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

A distributed control approach for power and energy management in a notional shipboard power system

NASA Astrophysics Data System (ADS)

Shen, Qunying

The main goal of this thesis is to present a power control module (PCON) based approach for power and energy management and to examine its control capability in shipboard power system (SPS). The proposed control scheme is implemented in a notional medium voltage direct current (MVDC) integrated power system (IPS) for electric ship. To realize the control functions such as ship mode selection, generator launch schedule, blackout monitoring, and fault ride-through, a PCON based distributed power and energy management system (PEMS) is developed. The control scheme is proposed as two-layer hierarchical architecture with system level on the top as the supervisory control and zonal level on the bottom as the decentralized control, which is based on the zonal distribution characteristic of the notional MVDC IPS that was proposed as one of the approaches for Next Generation Integrated Power System (NGIPS) by Norbert Doerry. Several types of modules with different functionalities are used to derive the control scheme in detail for the notional MVDC IPS. Those modules include the power generation module (PGM) that controls the function of generators, the power conversion module (PCM) that controls the functions of DC/DC or DC/AC converters, etc. Among them, the power control module (PCON) plays a critical role in the PEMS. It is the core of the control process. PCONs in the PEMS interact with all the other modules, such as power propulsion module (PPM), energy storage module (ESM), load shedding module (LSHED), and human machine interface (HMI) to realize the control algorithm in PEMS. The proposed control scheme is implemented in real time using the real time digital simulator (RTDS) to verify its validity. To achieve this, a system level energy storage module (SESM) and a zonal level energy storage module (ZESM) are developed in RTDS to cooperate with PCONs to realize the control functionalities. In addition, a load shedding module which takes into account the reliability of power supply (in terms of quality of service) is developed. This module can supply uninterruptible power to the mission critical loads. In addition, a multi-agent system (MAS) based framework is proposed to implement the PCON based PEMS through a hardware setup that is composed of MAMBA boards and FPGA interface. Agents are implemented using Java Agent DEvelopment Framework (JADE). Various test scenarios were tested to validate the approach.

Integrated modular teaching in dermatology for undergraduate students: A novel approach

PubMed Central

Karthikeyan, Kaliaperumal; Kumar, Annapurna

2014-01-01

Context: Undergraduate teaching in dermatology comprises didactic lectures and clinical classes. Integrated modular teaching is a novel approach, which integrates basic sciences with dermatology in the form of a module. Further the module also incorporates various teaching modalities, which facilitate active participation from students and promotes learning. The pre- and post-test values showed the effectiveness of the integrated module. The students feedback was encouraging. Aims: The aim of this study was to determine the acceptance and opinion of undergraduate students regarding integrated modular teaching as a new teaching aid in dermatology. Settings and Design: This was a descriptive study. Varied teaching methodologies involving multiple disciplines were undertaken in six major undergraduate topics in dermatology for seventh and eighth semester students. Materials and Methods: A total of six modules were conducted over a period of 12 months for students of seventh and eighth semesters. The topics for the various modules were sexually transmitted diseases, acquired immunodeficiency syndrome, oral ulcers, leprosy, connective tissue disorders and psoriasis. Faculty members from different disciplines participated. Pre- and post-test were conducted before and after the modules respectively to gauge the effectiveness of the modules. Results: It was found that almost every student had a better score on the posttest as compared to the pretest. General feedback obtained from the students showed that all of them felt that modular teaching was a more interesting and useful teaching learning experience than conventional teaching. Conclusions: Integrated modular teaching can be an effective adjunct in imparting theoretical and practical knowledge to the students. Further, various teaching methodologies can be used in integrated modules effectively with active student participation. Thus integrated modular teaching addresses two important issues in medical education, namely integration and active student participation. PMID:25165641

Integrated modular teaching in dermatology for undergraduate students: A novel approach.

PubMed

Karthikeyan, Kaliaperumal; Kumar, Annapurna

2014-07-01

Undergraduate teaching in dermatology comprises didactic lectures and clinical classes. Integrated modular teaching is a novel approach, which integrates basic sciences with dermatology in the form of a module. Further the module also incorporates various teaching modalities, which facilitate active participation from students and promotes learning. The pre- and post-test values showed the effectiveness of the integrated module. The students feedback was encouraging. The aim of this study was to determine the acceptance and opinion of undergraduate students regarding integrated modular teaching as a new teaching aid in dermatology. This was a descriptive study. Varied teaching methodologies involving multiple disciplines were undertaken in six major undergraduate topics in dermatology for seventh and eighth semester students. A total of six modules were conducted over a period of 12 months for students of seventh and eighth semesters. The topics for the various modules were sexually transmitted diseases, acquired immunodeficiency syndrome, oral ulcers, leprosy, connective tissue disorders and psoriasis. Faculty members from different disciplines participated. Pre- and post-test were conducted before and after the modules respectively to gauge the effectiveness of the modules. It was found that almost every student had a better score on the posttest as compared to the pretest. General feedback obtained from the students showed that all of them felt that modular teaching was a more interesting and useful teaching learning experience than conventional teaching. Integrated modular teaching can be an effective adjunct in imparting theoretical and practical knowledge to the students. Further, various teaching methodologies can be used in integrated modules effectively with active student participation. Thus integrated modular teaching addresses two important issues in medical education, namely integration and active student participation.

The nuclear lamina regulates germline stem cell niche organization via modulation of EGFR signaling.

PubMed

Chen, Haiyang; Chen, Xin; Zheng, Yixian

2013-07-03

Stem cell niche interactions have been studied extensively with regard to cell polarity and extracellular signaling. Less is known about the way in which signals and polarity cues integrate with intracellular structures to ensure appropriate niche organization and function. Here, we report that nuclear lamins function in the cyst stem cells (CySCs) of Drosophila testes to control the interaction of CySCs with the hub. This interaction is important for regulation of CySC differentiation and organization of the niche that supports the germline stem cells (GSCs). Lamin promotes nuclear retention of phosphorylated ERK in the CySC lineage by regulating the distribution of specific nucleoporins within the nuclear pores. Lamin-regulated nuclear epidermal growth factor (EGF) receptor signaling in the CySC lineage is essential for proliferation and differentiation of the GSCs and the transient amplifying germ cells. Thus, we have uncovered a role for the nuclear lamina in the integration of EGF signaling to regulate stem cell niche function. Copyright © 2013 Elsevier Inc. All rights reserved.

HTS-Net: An integrated regulome-interactome approach for establishing network regulation models in high-throughput screenings

PubMed Central

Rioualen, Claire; Da Costa, Quentin; Chetrit, Bernard; Charafe-Jauffret, Emmanuelle; Ginestier, Christophe

2017-01-01

High-throughput RNAi screenings (HTS) allow quantifying the impact of the deletion of each gene in any particular function, from virus-host interactions to cell differentiation. However, there has been less development for functional analysis tools dedicated to RNAi analyses. HTS-Net, a network-based analysis program, was developed to identify gene regulatory modules impacted in high-throughput screenings, by integrating transcription factors-target genes interaction data (regulome) and protein-protein interaction networks (interactome) on top of screening z-scores. HTS-Net produces exhaustive HTML reports for results navigation and exploration. HTS-Net is a new pipeline for RNA interference screening analyses that proves better performance than simple gene rankings by z-scores, by re-prioritizing genes and replacing them in their biological context, as shown by the three studies that we reanalyzed. Formatted input data for the three studied datasets, source code and web site for testing the system are available from the companion web site at http://htsnet.marseille.inserm.fr/. We also compared our program with existing algorithms (CARD and hotnet2). PMID:28949986

Towards a Web-Enabled Geovisualization and Analytics Platform for the Energy and Water Nexus

NASA Astrophysics Data System (ADS)

Sanyal, J.; Chandola, V.; Sorokine, A.; Allen, M.; Berres, A.; Pang, H.; Karthik, R.; Nugent, P.; McManamay, R.; Stewart, R.; Bhaduri, B. L.

2017-12-01

Interactive data analytics are playing an increasingly vital role in the generation of new, critical insights regarding the complex dynamics of the energy/water nexus (EWN) and its interactions with climate variability and change. Integration of impacts, adaptation, and vulnerability (IAV) science with emerging, and increasingly critical, data science capabilities offers a promising potential to meet the needs of the EWN community. To enable the exploration of pertinent research questions, a web-based geospatial visualization platform is being built that integrates a data analysis toolbox with advanced data fusion and data visualization capabilities to create a knowledge discovery framework for the EWN. The system, when fully built out, will offer several geospatial visualization capabilities including statistical visual analytics, clustering, principal-component analysis, dynamic time warping, support uncertainty visualization and the exploration of data provenance, as well as support machine learning discoveries to render diverse types of geospatial data and facilitate interactive analysis. Key components in the system architecture includes NASA's WebWorldWind, the Globus toolkit, postgresql, as well as other custom built software modules.

Transceivers and receivers for quantum key distribution and methods pertaining thereto

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

DeRose, Christopher; Sarovar, Mohan; Soh, Daniel B.S.

Various technologies for performing continuous-variable (CV) and discrete-variable (DV) quantum key distribution (QKD) with integrated electro-optical circuits are described herein. An integrated DV-QKD system uses Mach-Zehnder modulators to modulate a polarization of photons at a transmitter and select a photon polarization measurement basis at a receiver. An integrated CV-QKD system uses wavelength division multiplexing to send and receive amplitude-modulated and phase-modulated optical signals with a local oscillator signal while maintaining phase coherence between the modulated signals and the local oscillator signal.

Modeling coupled interactions of carbon, water, and ozone exchange between terrestrial ecosystems and the atmosphere. I: model description.

PubMed

Nikolov, Ned; Zeller, Karl F

2003-01-01

A new biophysical model (FORFLUX) is presented to study the simultaneous exchange of ozone, carbon dioxide, and water vapor between terrestrial ecosystems and the atmosphere. The model mechanistically couples all major processes controlling ecosystem flows trace gases and water implementing recent concepts in plant eco-physiology, micrometeorology, and soil hydrology. FORFLUX consists of four interconnected modules-a leaf photosynthesis model, a canopy flux model, a soil heat-, water- and CO2- transport model, and a snow pack model. Photosynthesis, water-vapor flux and ozone uptake at the leaf level are computed by the LEAFC3 sub-model. The canopy module scales leaf responses to a stand level by numerical integration of the LEAFC3model over canopy leaf area index (LAI). The integration takes into account (1) radiative transfer inside the canopy, (2) variation of foliage photosynthetic capacity with canopy depth, (3) wind speed attenuation throughout the canopy, and (4) rainfall interception by foliage elements. The soil module uses principles of the diffusion theory to predict temperature and moisture dynamics within the soil column, evaporation, and CO2 efflux from soil. The effect of soil heterogeneity on field-scale fluxes is simulated employing the Bresler-Dagan stochastic concept. The accumulation and melt of snow on the ground is predicted using an explicit energy balance approach. Ozone deposition is modeled as a sum of three fluxes- ozone uptake via plant stomata, deposition to non-transpiring plant surfaces, and ozone flux into the ground. All biophysical interactions are computed hourly while model projections are made at either hourly or daily time step. FORFLUX represents a comprehensive approach to studying ozone deposition and its link to carbon and water cycles in terrestrial ecosystems.

The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs.

PubMed

Rossi, Mario; Fasciani, Irene; Marampon, Francesco; Maggio, Roberto; Scarselli, Marco

2017-06-01

D 2 and D 3 dopamine receptors belong to the largest family of cell surface proteins in eukaryotes, the G protein-coupled receptors (GPCRs). Considering their crucial physiologic functions and their relatively accessible cellular locations, GPCRs represent one of the most important classes of therapeutic targets. Until recently, the only strategy to develop drugs regulating GPCR activity was through the identification of compounds that directly acted on the orthosteric sites for endogenous ligands. However, many efforts have recently been made to identify small molecules that are able to interact with allosteric sites. These sites are less well-conserved, therefore allosteric ligands have greater selectivity on the specific receptor. Strikingly, the use of allosteric modulators can provide specific advantages, such as an increased selectivity for GPCR subunits and the ability to introduce specific beneficial therapeutic effects without disrupting the integrity of complex physiologically regulated networks. In 2010, our group unexpectedly found that N -[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide (SB269652), a compound supposed to interact with the orthosteric binding site of dopamine receptors, was actually a negative allosteric modulator of D 2 - and D 3 -receptor dimers, thus identifying the first allosteric small molecule acting on these important therapeutic targets. This review addresses the progress in understanding the molecular mechanisms of interaction between the negative modulator SB269652 and D 2 and D 3 dopamine receptor monomers and dimers, and surveys the prospects for developing new dopamine receptor allosteric drugs with SB269652 as the leading compound. U.S. Government work not protected by U.S. copyright.

Integration of carbon nanotubes in slot waveguides (Conference Presentation)

NASA Astrophysics Data System (ADS)

Durán-Valdeiglesias, Elena; Zhang, Weiwei; Hoang, Thi Hong Cam; Alonso-Ramos, Carlos; Serna, Samuel; Le Roux, Xavier; Cassan, Eric; Balestrieri, Matteo; Keita, Al-Saleh; Sarti, Francesco; Biccari, Francesco; Torrini, Ughetta; Vinattieri, Anna; Yang, Hongliu; Bezugly, Viktor; Cuniberti, Gianaurelio; Filoramo, Arianna; Gurioli, Massimo; Vivien, Laurent

2016-05-01

Demanding applications such as video streaming, social networking, or web search relay on a large network of data centres, interconnected through optical links. The ever-growing data rates and power consumption inside these data centres are pushing copper links close to their fundamental limits. Optical interconnects are being extensively studied with the purpose of solving these limitations. Among the different possible technology platforms, silicon photonics, due to its compatibility with the CMOS platform, has become one of the preferred solutions for the development of the future generation photonic interconnects. However, the on-chip integration of all photonic and optoelectronic building blocks (sources, modulators and detectors…) is very complex and is not cost-effective due to the various materials involved (Ge for detection, doped Si for modulators and III-V for lasing). Carbon nanotubes (CNTs) are nanomaterials of great interest in photonics thanks to their fundamental optical properties, including near-IR room-temperature foto- and electro- luminescence, Stark effect, Kerr effect and absorption. In consequence, CNTs have the ability to emit, modulate and detect light in the telecommunications wavelength range. Furthermore, they are being extensively developed for new nano-electronics applications. In this work, we propose to use CNTs as active material integrated into silicon photonics for the development of all optoelectronic devices. Here, we report on the development of new integration schemes to couple the light emission from CNTs into optical resonators implemented on the silicon-on-insulator and silicon-nitride-on-insulator platforms. A theoretical and experimental analysis of the light interaction of CNTs with micro-ring resonators based on strip and slot waveguides and slot photonic crystal heterostructure cavities were carried out.

Engaging Undergraduates in Soil Sustainability Decision-Making through an InTeGrate Module

ERIC Educational Resources Information Center

Fortner, Sarah K.; Scherer, Hannah H.; Murphy, Martha A.

2016-01-01

Continued agricultural productivity hinges on understanding how to manage soil resources. A 2-week undergraduate introductory-level module: "A Growing Concern: Sustaining Soil Resources Through Local Decision Making" was collaboratively developed through the InTeGrate Project. InTeGrate modules and courses engage students in grand…

[CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

PubMed

Sizonov, V A; Dmitrieva, L E; Kuznetsov, S V

2015-01-01

Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules

NASA Astrophysics Data System (ADS)

Menon, Govind; Krishnan, J.

2016-07-01

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules.

PubMed

Menon, Govind; Krishnan, J

2016-07-21

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

Learning through student-authored interactive media: A mixed methods exploration

NASA Astrophysics Data System (ADS)

Sakai-Miller, Sharon (Sam)

2009-12-01

The purpose of this study was to improve student achievement in science and proficiency in information and communication technologies (ICT), which are vital 21st century workforce skills. Instead of isolating the issues, the study proposed an integrated solution that applied the constructivist approach to help students learn about a unit in biology using three software applications to create interactive, self-correcting eModules within a two-week period. Research questions focused on the effectiveness of the instructional strategy, the experience of students authoring eModules, obstacles they encountered, and the role of the teacher. Fifty-one out of the possible 55 eleventh and twelfth grade students in the two Advanced Biology classes consented to participate in the study. A comparison of pre and post-test scores showed an average 547% improvement. Students with low initial scores of 10% or less improved an average of 1229%. Ten students (20%) went from 20% or below on the pre-test to 80% or above on the post-test, and were analyzed as a subgroup called "big gainers." Student journals and exit surveys were explored to understand the process students followed to develop eModules. The majority of student responses in the exit survey (85%) described the overall experience as a positive one. Journals showed how students were able to follow the process of creating a concept map using Inspiration software, converting the outline into a PowerPoint slide show, editing the slides and importing them into Adobe Captivate files, inserting self-correcting questions, completing their eModules, and submitting them to their teacher. Students identified obstacles they encountered to help them to problem solve and provided data for improving the instructional strategy. Addressing technology learning objectives within the context and pacing of a content area class was accomplished, but it required providing a collaborative learning environment, an appropriate task, mediating tools, and assessment. The data analysis suggests that the instructional strategy of student-authored eModules had a positive impact on learning science content and ICT proficiencies. Historically students have been consumers of interactive media or producers of presentational media. This study suggests that they will learn more when they are the authors of interactive media.

Clinically oriented three-year medical physics curriculum: a new design for the future.

PubMed

Nachiappan, Arun C; Lee, Stephen R; Willis, Marc H; Galfione, Matthew R; Chinnappan, Raj R; Diaz-Marchan, Pedro J; Bushong, Stewart C

2012-09-01

Medical physics instruction for diagnostic radiology residency at our institution has been redesigned with an interactive and image-based approach that encourages clinical application. The new medical physics curriculum spans the first 3 years of radiology residency and is integrated with the core didactic curriculum. Salient features include clinical medical physics conferences, fundamentals of medical physics lectures, practicums, online modules, journal club, and a final review before the American Board of Radiology core examination.

Electrical Prototype Power Processor for the 30-cm Mercury electric propulsion engine

NASA Technical Reports Server (NTRS)

Biess, J. J.; Frye, R. J.

1978-01-01

An Electrical Prototpye Power Processor has been designed to the latest electrical and performance requirements for a flight-type 30-cm ion engine and includes all the necessary power, command, telemetry and control interfaces for a typical electric propulsion subsystem. The power processor was configured into seven separate mechanical modules that would allow subassembly fabrication, test and integration into a complete power processor unit assembly. The conceptual mechanical packaging of the electrical prototype power processor unit demonstrated the relative location of power, high voltage and control electronic components to minimize electrical interactions and to provide adequate thermal control in a vacuum environment. Thermal control was accomplished with a heat pipe simulator attached to the base of the modules.

Intrinsic functional network architecture of human semantic processing: Modules and hubs.

PubMed

Xu, Yangwen; Lin, Qixiang; Han, Zaizhu; He, Yong; Bi, Yanchao

2016-05-15

Semantic processing entails the activation of widely distributed brain areas across the temporal, parietal, and frontal lobes. To understand the functional structure of this semantic system, we examined its intrinsic functional connectivity pattern using a database of 146 participants. Focusing on areas consistently activated during semantic processing generated from a meta-analysis of 120 neuroimaging studies (Binder et al., 2009), we found that these regions were organized into three stable modules corresponding to the default mode network (Module DMN), the left perisylvian network (Module PSN), and the left frontoparietal network (Module FPN). These three dissociable modules were integrated by multiple connector hubs-the left angular gyrus (AG) and the left superior/middle frontal gyrus linking all three modules, the left anterior temporal lobe linking Modules DMN and PSN, the left posterior portion of dorsal intraparietal sulcus (IPS) linking Modules DMN and FPN, and the left posterior middle temporal gyrus (MTG) linking Modules PSN and FPN. Provincial hubs, which converge local information within each system, were also identified: the bilateral posterior cingulate cortices/precuneus, the bilateral border area of the posterior AG and the superior lateral occipital gyrus for Module DMN; the left supramarginal gyrus, the middle part of the left MTG and the left orbital inferior frontal gyrus (IFG) for Module FPN; and the left triangular IFG and the left IPS for Module FPN. A neuro-functional model for semantic processing was derived based on these findings, incorporating the interactions of memory, language, and control. Copyright © 2016 Elsevier Inc. All rights reserved.

Multimedia in the informed consent process for endoscopic sinus surgery: A randomized control trial.

PubMed

Siu, Jennifer M; Rotenberg, Brian W; Franklin, Jason H; Sowerby, Leigh J

2016-06-01

To determine patient recall of specific risks associated with endoscopic sinus surgery and whether an adjunct multimedia education module is an effective patient tool in enhancing the standard informed consent process. Prospective, randomized, controlled trial. Fifty consecutive adult patients scheduled for endoscopic sinus surgery at a rhinology clinic of a tertiary care hospital were recruited for this study. Informed consent was studied by comparing the number of risks recalled when patients had a verbal discussion in conjunction with a 6-minute interactive module or the verbal discussion alone. Early recall was measured immediately following the informed consent process, and delayed recall was measured 3 to 4 weeks after patient preference details were also collected. Early risk recall in the multimedia group was significantly higher than the control group (P = .0036); however, there was no difference between the groups in delayed risk recall. Seventy-six percent of participants expressed interest in viewing the multimedia module if available online between the preoperative and procedural day. Sixty-eight percent of patients preferred having the multimedia module as an adjunct to the informed consent process as opposed to the multimedia consent process alone. There is an early improvement in overall risk recall in patients who complete an interactive multimedia module, with a clear patient preference for this method. Here we emphasize the well-known challenges of patient education and demonstrate the effectiveness of integrating technology into clinical practice in order to enhance the informed consent process. 1b Laryngoscope, 126:1273-1278, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

A Network-Based Classification Model for Deriving Novel Drug-Disease Associations and Assessing Their Molecular Actions

PubMed Central

Oh, Min; Ahn, Jaegyoon; Yoon, Youngmi

2014-01-01

The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug) was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively) in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer’s disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer’s disease. PMID:25356910

A Usability Study of Interactive Web-Based Modules

ERIC Educational Resources Information Center

Girard, Tulay; Pinar, Musa

2011-01-01

This research advances the understanding of the usability of marketing case study modules in the area of interactive web-based technologies through the assignment of seven interactive case modules in a Principles of Marketing course. The case modules were provided for marketing students by the publisher, McGraw Hill Irwin, of the…

Computational framework to support integration of biomolecular and clinical data within a translational approach.

PubMed

Miyoshi, Newton Shydeo Brandão; Pinheiro, Daniel Guariz; Silva, Wilson Araújo; Felipe, Joaquim Cezar

2013-06-06

The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. We have implemented an extension of Chado - the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an ontology; the Extraction, Transformation and Load (ETL) process to extract the data from the source clinical database and load it in the Clinical Module of Chado; the development of a web tool and a Bridge Layer to adapt the web tool to Chado, as well as other applications. Open-source computational solutions currently available for translational science does not have a model to represent biomolecular information and also are not integrated with the existing bioinformatics tools. On the other hand, existing genomic data models do not represent clinical patient data. A framework was developed to support translational research by integrating biomolecular information coming from different "omics" technologies with patient's clinical and socio-demographic data. This framework should present some features: flexibility, compression and robustness. The experiments accomplished from a use case demonstrated that the proposed system meets requirements of flexibility and robustness, leading to the desired integration. The Clinical Module can be accessed in http://dcm.ffclrp.usp.br/caib/pg=iptrans.

VINE-A NUMERICAL CODE FOR SIMULATING ASTROPHYSICAL SYSTEMS USING PARTICLES. I. DESCRIPTION OF THE PHYSICS AND THE NUMERICAL METHODS

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

Wetzstein, M.; Nelson, Andrew F.; Naab, T.

2009-10-01

We present a numerical code for simulating the evolution of astrophysical systems using particles to represent the underlying fluid flow. The code is written in Fortran 95 and is designed to be versatile, flexible, and extensible, with modular options that can be selected either at the time the code is compiled or at run time through a text input file. We include a number of general purpose modules describing a variety of physical processes commonly required in the astrophysical community and we expect that the effort required to integrate additional or alternate modules into the code will be small. Inmore » its simplest form the code can evolve the dynamical trajectories of a set of particles in two or three dimensions using a module which implements either a Leapfrog or Runge-Kutta-Fehlberg integrator, selected by the user at compile time. The user may choose to allow the integrator to evolve the system using individual time steps for each particle or with a single, global time step for all. Particles may interact gravitationally as N-body particles, and all or any subset may also interact hydrodynamically, using the smoothed particle hydrodynamic (SPH) method by selecting the SPH module. A third particle species can be included with a module to model massive point particles which may accrete nearby SPH or N-body particles. Such particles may be used to model, e.g., stars in a molecular cloud. Free boundary conditions are implemented by default, and a module may be selected to include periodic boundary conditions. We use a binary 'Press' tree to organize particles for rapid access in gravity and SPH calculations. Modules implementing an interface with special purpose 'GRAPE' hardware may also be selected to accelerate the gravity calculations. If available, forces obtained from the GRAPE coprocessors may be transparently substituted for those obtained from the tree, or both tree and GRAPE may be used as a combination GRAPE/tree code. The code may be run without modification on single processors or in parallel using OpenMP compiler directives on large-scale, shared memory parallel machines. We present simulations of several test problems, including a merger simulation of two elliptical galaxies with 800,000 particles. In comparison to the Gadget-2 code of Springel, the gravitational force calculation, which is the most costly part of any simulation including self-gravity, is {approx}4.6-4.9 times faster with VINE when tested on different snapshots of the elliptical galaxy merger simulation when run on an Itanium 2 processor in an SGI Altix. A full simulation of the same setup with eight processors is a factor of 2.91 faster with VINE. The code is available to the public under the terms of the Gnu General Public License.« less

Vine—A Numerical Code for Simulating Astrophysical Systems Using Particles. I. Description of the Physics and the Numerical Methods

NASA Astrophysics Data System (ADS)

Wetzstein, M.; Nelson, Andrew F.; Naab, T.; Burkert, A.

2009-10-01

We present a numerical code for simulating the evolution of astrophysical systems using particles to represent the underlying fluid flow. The code is written in Fortran 95 and is designed to be versatile, flexible, and extensible, with modular options that can be selected either at the time the code is compiled or at run time through a text input file. We include a number of general purpose modules describing a variety of physical processes commonly required in the astrophysical community and we expect that the effort required to integrate additional or alternate modules into the code will be small. In its simplest form the code can evolve the dynamical trajectories of a set of particles in two or three dimensions using a module which implements either a Leapfrog or Runge-Kutta-Fehlberg integrator, selected by the user at compile time. The user may choose to allow the integrator to evolve the system using individual time steps for each particle or with a single, global time step for all. Particles may interact gravitationally as N-body particles, and all or any subset may also interact hydrodynamically, using the smoothed particle hydrodynamic (SPH) method by selecting the SPH module. A third particle species can be included with a module to model massive point particles which may accrete nearby SPH or N-body particles. Such particles may be used to model, e.g., stars in a molecular cloud. Free boundary conditions are implemented by default, and a module may be selected to include periodic boundary conditions. We use a binary "Press" tree to organize particles for rapid access in gravity and SPH calculations. Modules implementing an interface with special purpose "GRAPE" hardware may also be selected to accelerate the gravity calculations. If available, forces obtained from the GRAPE coprocessors may be transparently substituted for those obtained from the tree, or both tree and GRAPE may be used as a combination GRAPE/tree code. The code may be run without modification on single processors or in parallel using OpenMP compiler directives on large-scale, shared memory parallel machines. We present simulations of several test problems, including a merger simulation of two elliptical galaxies with 800,000 particles. In comparison to the Gadget-2 code of Springel, the gravitational force calculation, which is the most costly part of any simulation including self-gravity, is ~4.6-4.9 times faster with VINE when tested on different snapshots of the elliptical galaxy merger simulation when run on an Itanium 2 processor in an SGI Altix. A full simulation of the same setup with eight processors is a factor of 2.91 faster with VINE. The code is available to the public under the terms of the Gnu General Public License.

Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

PubMed

Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

2017-12-15

Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM-receptor interaction" were remarked significant (adjusted p<0.001). Genes enriched in these pathways coupled with their regulatory miRNAs formed a functional miRNA-gene regulatory module that contains 7 miRNAs, 22 genes and 42 miRNA-gene connections. Gene interaction analysis based on String database revealed that 8 out of 22 genes were highly clustered. Finally, we experimentally confirmed a functional regulatory module containing 5 miRNAs (miR-130b-3p, miR-148a-3p, miR-345-5p, miR-378a-3p, and miR-422a) and 6 genes (COL6A1, COL6A2, COL6A3, PIK3R3, COL1A1, CCND2) associated with liver fibrosis. Our integrated analysis of miRNA and gene expression profiles highlighted a functional miRNA-gene regulatory module associated with liver fibrosis, which, to some extent, may provide important clues to better understand the underlying pathogenesis of liver fibrosis. Copyright © 2017. Published by Elsevier B.V.

Multi-Dimensional Prioritization of Dental Caries Candidate Genes and Its Enriched Dense Network Modules

PubMed Central

Wang, Quan; Jia, Peilin; Cuenco, Karen T.; Feingold, Eleanor; Marazita, Mary L.; Wang, Lily; Zhao, Zhongming

2013-01-01

A number of genetic studies have suggested numerous susceptibility genes for dental caries over the past decade with few definite conclusions. The rapid accumulation of relevant information, along with the complex architecture of the disease, provides a challenging but also unique opportunity to review and integrate the heterogeneous data for follow-up validation and exploration. In this study, we collected and curated candidate genes from four major categories: association studies, linkage scans, gene expression analyses, and literature mining. Candidate genes were prioritized according to the magnitude of evidence related to dental caries. We then searched for dense modules enriched with the prioritized candidate genes through their protein-protein interactions (PPIs). We identified 23 modules comprising of 53 genes. Functional analyses of these 53 genes revealed three major clusters: cytokine network relevant genes, matrix metalloproteinases (MMPs) family, and transforming growth factor-beta (TGF-β) family, all of which have been previously implicated to play important roles in tooth development and carious lesions. Through our extensive data collection and an integrative application of gene prioritization and PPI network analyses, we built a dental caries-specific sub-network for the first time. Our study provided insights into the molecular mechanisms underlying dental caries. The framework we proposed in this work can be applied to other complex diseases. PMID:24146904

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

Genomic Analysis of Circadian Clock-, Light-, and Growth-Correlated Genes Reveals PHYTOCHROME-INTERACTING FACTOR5 as a Modulator of Auxin Signaling in Arabidopsis1[C][W][OA

PubMed Central

Nozue, Kazunari; Harmer, Stacey L.; Maloof, Julin N.

2011-01-01

Plants exhibit daily rhythms in their growth, providing an ideal system for the study of interactions between environmental stimuli such as light and internal regulators such as the circadian clock. We previously found that two basic loop-helix-loop transcription factors, PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and PIF5, integrate light and circadian clock signaling to generate rhythmic plant growth in Arabidopsis (Arabidopsis thaliana). Here, we use expression profiling and real-time growth assays to identify growth regulatory networks downstream of PIF4 and PIF5. Genome-wide analysis of light-, clock-, or growth-correlated genes showed significant overlap between the transcriptomes of clock-, light-, and growth-related pathways. Overrepresentation analysis of growth-correlated genes predicted that the auxin and gibberellic acid (GA) hormone pathways both contribute to diurnal growth control. Indeed, lesions of GA biosynthesis genes retarded rhythmic growth. Surprisingly, GA-responsive genes are not enriched among genes regulated by PIF4 and PIF5, whereas auxin pathway and response genes are. Consistent with this finding, the auxin response is more severely affected than the GA response in pif4 pif5 double mutants and in PIF5-overexpressing lines. We conclude that at least two downstream modules participate in diurnal rhythmic hypocotyl growth: PIF4 and/or PIF5 modulation of auxin-related pathways and PIF-independent regulation of the GA pathway. PMID:21430186

"iBIM"--internet-based interactive modules: an easy and interesting learning tool for general surgery residents.

PubMed

Azer, Nader; Shi, Xinzhe; de Gara, Chris; Karmali, Shahzeer; Birch, Daniel W

2014-04-01

The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching. Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores. Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020). Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.

Neural dynamics of social tie formation in economic decision-making.

PubMed

Bault, Nadège; Pelloux, Benjamin; Fahrenfort, Johannes J; Ridderinkhof, K Richard; van Winden, Frans

2015-06-01

The disposition for prosocial conduct, which contributes to cooperation as arising during social interaction, requires cortical network dynamics responsive to the development of social ties, or care about the interests of specific interaction partners. Here, we formulate a dynamic computational model that accurately predicted how tie formation, driven by the interaction history, influences decisions to contribute in a public good game. We used model-driven functional MRI to test the hypothesis that brain regions key to social interactions keep track of dynamics in tie strength. Activation in the medial prefrontal cortex (mPFC) and posterior cingulate cortex tracked the individual's public good contributions. Activation in the bilateral posterior superior temporal sulcus (pSTS), and temporo-parietal junction was modulated parametrically by the dynamically developing social tie-as estimated by our model-supporting a role of these regions in social tie formation. Activity in these two regions further reflected inter-individual differences in tie persistence and sensitivity to behavior of the interaction partner. Functional connectivity between pSTS and mPFC activations indicated that the representation of social ties is integrated in the decision process. These data reveal the brain mechanisms underlying the integration of interaction dynamics into a social tie representation which in turn influenced the individual's prosocial decisions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Control of Recombination Directionality by the Listeria Phage A118 Protein Gp44 and the Coiled-Coil Motif of Its Serine Integrase.

PubMed

Mandali, Sridhar; Gupta, Kushol; Dawson, Anthony R; Van Duyne, Gregory D; Johnson, Reid C

2017-06-01

The serine integrase of phage A118 catalyzes integrative recombination between attP on the phage and a specific attB locus on the chromosome of Listeria monocytogenes , but it is unable to promote excisive recombination between the hybrid attL and attR sites found on the integrated prophage without assistance by a recombination directionality factor (RDF). We have identified and characterized the phage-encoded RDF Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination. This interaction is sufficient to inhibit integration, but a second interaction involving the N-terminal end of Gp44 is also required to activate excision. We provide evidence that these two contacts modulate the trajectory of the CC motifs as they extend out from the integrase core in a manner dependent upon the identities of the four att sites. Our results support a model whereby Gp44 shapes the Int-bound complexes to control which att sites can synapse and recombine. IMPORTANCE Serine integrases mediate directional recombination between bacteriophage and bacterial chromosomes. These highly regulated site-specific recombination reactions are integral to the life cycle of temperate phage and, in the case of Listeria monocytogenes lysogenized by A118 family phage, are an essential virulence determinant. Serine integrases are also utilized as tools for genetic engineering and synthetic biology because of their exquisite unidirectional control of the DNA exchange reaction. Here, we identify and characterize the recombination directionality factor (RDF) that activates excision and inhibits integration reactions by the phage A118 integrase. We provide evidence that the A118 RDF binds to and modulates the trajectory of the long coiled-coil motif that extends from the large carboxyl-terminal DNA binding domain and is postulated to control the early steps of recombination site synapsis. Copyright © 2017 American Society for Microbiology.

Integration of a Communicating Science Module into an Advanced Chemistry Laboratory Course

ERIC Educational Resources Information Center

Renaud, Jessica; Squier, Christopher; Larsen, Sarah C.

2006-01-01

A communicating science module was introduced into an advanced undergraduate physical chemistry laboratory course. The module was integrated into the course such that students received formal instruction in communicating science interwoven with the chemistry laboratory curriculum. The content of the communicating science module included three…

Integration of an expert teaching assistant with distance learning software

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

Fonseca, S.P.; Reed, N.E.

1996-12-31

The Remote Teaching Assistant (RTA) software currently under development at UC Davis allows students and Teaching Assistants (TA`s) to interact through multimedia communication via the Internet. To resolve the problem of TA unavailability and limited knowledge, an Expert Teaching Assistant (ETA) module is being developed. When TA`s are not on-line, students in need of help consult ETA. The focus of this research is the development and integration of ETA with RTA, the establishment of an architecture suitable for use with education (the domain) in any sub-domain (course), and the creation of a mechanism usable by non-technical personnel to maintain knowledgemore » bases.« less

ATLAS, an integrated structural analysis and design system. Volume 3: User's manual, input and execution data

NASA Technical Reports Server (NTRS)

Dreisbach, R. L. (Editor)

1979-01-01

The input data and execution control statements for the ATLAS integrated structural analysis and design system are described. It is operational on the Control Data Corporation (CDC) 6600/CYBER computers in a batch mode or in a time-shared mode via interactive graphic or text terminals. ATLAS is a modular system of computer codes with common executive and data base management components. The system provides an extensive set of general-purpose technical programs with analytical capabilities including stiffness, stress, loads, mass, substructuring, strength design, unsteady aerodynamics, vibration, and flutter analyses. The sequence and mode of execution of selected program modules are controlled via a common user-oriented language.

Uniform strongly interacting soliton gas in the frame of the Nonlinear Schrodinger Equation

NASA Astrophysics Data System (ADS)

Gelash, Andrey; Agafontsev, Dmitry

2017-04-01

The statistical properties of many soliton systems play the key role in the fundamental studies of integrable turbulence and extreme sea wave formation. It is well known that separated solitons are stable nonlinear coherent structures moving with constant velocity. After collisions with each other they restore the original shape and only acquire an additional phase shift. However, at the moment of strong nonlinear soliton interaction (i.e. when solitons are located close) the wave field are highly complicated and should be described by the theory of inverse scattering transform (IST), which allows to integrate the KdV equation, the NLSE and many other important nonlinear models. The usual approach of studying the dynamics and statistics of soliton wave field is based on relatively rarefied gas of solitons [1,2] or restricted by only two-soliton interactions [3]. From the other hand, the exceptional role of interacting solitons and similar coherent structures - breathers in the formation of rogue waves statistics was reported in several recent papers [4,5]. In this work we study the NLSE and use the most straightforward and general way to create many soliton initial condition - the exact N-soliton formulas obtained in the theory of the IST [6]. We propose the recursive numerical scheme for Zakharov-Mikhailov variant of the dressing method [7,8] and discuss its stability with respect to increasing the number of solitons. We show that the pivoting, i.e. the finding of an appropriate order for recursive operations, has a significant impact on the numerical accuracy. We use the developed scheme to generate statistical ensembles of 32 strongly interacting solitons, i.e. solve the inverse scattering problem for the high number of discrete eigenvalues. Then we use this ensembles as initial conditions for numerical simulations in the box with periodic boundary conditions and study statics of obtained uniform strongly interacting gas of NLSE solitons. Author thanks the support of the Russian Science Foundation (Grand No. 14-22-00174) [1] D. Dutykh, E. Pelinovsky, Numerical simulation of a solitonic gas in kdv and kdv-bbm equations, Physics Letters A 378 (42) (2014) 3102-3110. [2] E. Shurgalina, E. Pelinovsky, Nonlinear dynamics of a soliton gas: Modified korteweg-de vries equation framework, Physics Letters A 380 (24) (2016) 2049-2053. [3] E. N. Pelinovsky, E. Shurgalina, A. Sergeeva, T. G. Talipova, G. El, R. H. Grimshaw, Two-soliton interaction as an elementary act of soliton turbulence in integrable systems, Physics Letters A 377 (3) (2013) 272-275 [4] J. Soto-Crespo, N. Devine, N. Akhmediev, Integrable turbulence and rogue waves: Breathers or solitons?, Physical review letters 116 (10) (2016) 103901. [5] D. S. Agafontsev, V. E. Zakharov, Integrable turbulence and formation of rogue waves, Nonlinearity 28 (8) (2015) 2791. [6] V. E. Zakharov, A. B. Shabat, Exact theory of two-dimensional self-focusing and one-dimensional self-modulation of waves in nonlinear media, Soviet Physics JETP 34 (1) (1972) 62. [7] V. Zakharov, A. Mikhailov, Relativistically invariant two-dimensional models of field theory which are integrable by means of the inverse scattering problem method, Sov. Phys.-JETP (Engl. Transl.) 47 (6) (1978). [8] A. A. Gelash, V. E. Zakharov, Superregular solitonic solutions: a novel scenario for the nonlinear stage of modulation instability, Nonlinearity 27 (4) (2014) R1.

Electrically Tunable Integrated Thin-Film Magnetoelectric Resonators

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

El-Ghazaly, Amal; Evans, Joseph T.; Sato, Noriyuki

Magnetoelectrics have attracted much attention for their ability to control magnetic behavior electrically and electrical behavior magnetically. This feature provides numerous benefits to electronic systems and can potentially serve as the bridge needed to integrate magnetic devices into mainstream electronics. This natural next step is pursued and thin-film integrated magnetoelectric devices are produced for radio-frequency (RF) electronics. The first fully integrated, thin-film magnetoelectric modulators for tunable RF electronics are presented. Moreover, these devices provide electric field control of magnetic permeability in order to change the phase velocity and resonance frequency of coplanar waveguides. During this study, the various thin-film materialmore » phenomena, trade-offs, and integration considerations for composite magnetoelectrics are analyzed and discussed. The fabricated devices achieve reversible tunability of the resonance frequency, characterized by a remarkable converse magnetoelectric coupling coefficient of up to 24 mG cm V -1 using just thin films. Based on this work, suggestions are given for additional optimizations of future designs that will maximize the thin-film magnetoelectric interactions.« less

Electrically Tunable Integrated Thin-Film Magnetoelectric Resonators

DOE PAGES

El-Ghazaly, Amal; Evans, Joseph T.; Sato, Noriyuki; ...

2017-06-14

Magnetoelectrics have attracted much attention for their ability to control magnetic behavior electrically and electrical behavior magnetically. This feature provides numerous benefits to electronic systems and can potentially serve as the bridge needed to integrate magnetic devices into mainstream electronics. This natural next step is pursued and thin-film integrated magnetoelectric devices are produced for radio-frequency (RF) electronics. The first fully integrated, thin-film magnetoelectric modulators for tunable RF electronics are presented. Moreover, these devices provide electric field control of magnetic permeability in order to change the phase velocity and resonance frequency of coplanar waveguides. During this study, the various thin-film materialmore » phenomena, trade-offs, and integration considerations for composite magnetoelectrics are analyzed and discussed. The fabricated devices achieve reversible tunability of the resonance frequency, characterized by a remarkable converse magnetoelectric coupling coefficient of up to 24 mG cm V -1 using just thin films. Based on this work, suggestions are given for additional optimizations of future designs that will maximize the thin-film magnetoelectric interactions.« less

Structural Biology of Non-Ribosomal Peptide Synthetases

PubMed Central

Miller, Bradley R.; Gulick, Andrew M.

2016-01-01

Summary The non-ribosomal peptide synthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic amino acid substrates. Within a single module are multiple catalytic domains that are responsible for incorporation of a single residue. After the amino acid is activated and covalently attached to an integrated carrier protein domain, the substrates and intermediates are delivered to neighboring catalytic domains for peptide bond formation or, in some modules, chemical modification. In the final module, the peptide is delivered to a terminal thioesterase domain that catalyzes release of the peptide product. This multi-domain modular architecture raises questions about the structural features that enable this assembly line synthesis in an efficient manner. The structures of the core component domains have been determined and demonstrate insights into the catalytic activity. More recently, multi-domain structures have been determined and are providing clues to the features of these enzyme systems that govern the functional interaction between multiple domains. This chapter describes the structures of NRPS proteins and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains. PMID:26831698

Plasmonic interferometers: From physics to biosensing applications

NASA Astrophysics Data System (ADS)

Zeng, Xie

Optical interferometry has a long history and wide range of applications. In recent years, plasmonic interferometer arouses great interest due to its compact size and enhanced light-matter interaction. They have demonstrated attractive applications in biomolecule sensing, optical modulation/switching, and material characterization, etc. In this work, we first propose a practical far-field method to extract the intrinsic phase dispersion, revealing important phase information during interactions among free-space light, nanostructure, and SPs. The proposed approach is confirmed by both simulation and experiment. Then we design novel plasmonic interferometer structure for sensitive optical sensing applications. To overcome two major limitations suffered by previously reported double-slit plasmonic Mach-Zehnder interferometer (PMZI), two new schemes are proposed and investigated. (1) A PMZI based on end-fire coupling improves the SP coupling efficiency and enhance the interference contrast more than 50 times. (2) In another design, a multi-layered metal-insulator-metal PMZI releases the requirement for single-slit illumination, which enables sensitive, high-throughput sensing applications based on intensity modulation. We develop a sensitive, low-cost and high-throughput biosensing platform based on intensity modulation using ring-hole plasmonic interferometers. This biosensor is then integrated with cell-phone-based microscope, which is promising to develop a portable sensor for point-of-care diagnostics, epidemic disease control and food safety monitoring.

Norepinephrine versus Dopamine and their Interaction in Modulating Synaptic Function in the Prefrontal Cortex

PubMed Central

Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

2016-01-01

Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. PMID:26790349

DREAM (Downstream Regulatory Element Antagonist Modulator) contributes to synaptic depression and contextual fear memory

PubMed Central

2010-01-01

The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory. PMID:20205763

Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation.

PubMed

Mitrea, Diana M; Cika, Jaclyn A; Stanley, Christopher B; Nourse, Amanda; Onuchic, Paulo L; Banerjee, Priya R; Phillips, Aaron H; Park, Cheon-Gil; Deniz, Ashok A; Kriwacki, Richard W

2018-02-26

Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid-liquid phase separation (LLPS) via heterotypic interactions with nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), and is integral to the liquid-like nucleolar matrix. Here we show that NPM1 can also undergo LLPS via homotypic interactions between its polyampholytic intrinsically disordered regions, a mechanism that opposes LLPS via heterotypic interactions. Using a combination of biophysical techniques, including confocal microscopy, SAXS, analytical ultracentrifugation, and single-molecule fluorescence, we describe how conformational changes within NPM1 control valency and switching between the different LLPS mechanisms. We propose that this newly discovered interplay between multiple LLPS mechanisms may influence the direction of vectorial pre-ribosomal particle assembly within, and exit from the nucleolus as part of the ribosome biogenesis process.

Predicting disease-related proteins based on clique backbone in protein-protein interaction network.

PubMed

Yang, Lei; Zhao, Xudong; Tang, Xianglong

2014-01-01

Network biology integrates different kinds of data, including physical or functional networks and disease gene sets, to interpret human disease. A clique (maximal complete subgraph) in a protein-protein interaction network is a topological module and possesses inherently biological significance. A disease-related clique possibly associates with complex diseases. Fully identifying disease components in a clique is conductive to uncovering disease mechanisms. This paper proposes an approach of predicting disease proteins based on cliques in a protein-protein interaction network. To tolerate false positive and negative interactions in protein networks, extending cliques and scoring predicted disease proteins with gene ontology terms are introduced to the clique-based method. Precisions of predicted disease proteins are verified by disease phenotypes and steadily keep to more than 95%. The predicted disease proteins associated with cliques can partly complement mapping between genotype and phenotype, and provide clues for understanding the pathogenesis of serious diseases.

Hunger and thirst interact to regulate ingestive behavior in flies and mammals.

PubMed

Jourjine, Nicholas

2017-05-01

In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact. © 2017 WILEY Periodicals, Inc.

Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome

PubMed Central

Kuwano, Yuki; Nishida, Kensei; Akaike, Yoko; Kurokawa, Ken; Nishikawa, Tatsuya; Masuda, Kiyoshi; Rokutan, Kazuhito

2016-01-01

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase that phosphorylates and activates the apoptotic program through interaction with diverse downstream targets including tumor suppressor p53. HIPK2 is activated by genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage response (DDR) is triggered by DNA lesions or chromatin alterations. The DDR regulates DNA repair, cell cycle checkpoint activation, and apoptosis to restore genome integrity and cellular homeostasis. Maintenance of the DDR is essential to prevent development of diseases caused by genomic instability, including cancer, defects of development, and neurodegenerative disorders. Recent studies reveal a novel HIPK2-mediated pathway for DDR through interaction with chromatin remodeling factor homeodomain protein 1γ. In this review, we will highlight the molecular mechanisms of HIPK2 and show its functions as a crucial DDR regulator. PMID:27689990

Vertical electro-absorption modulator design and its integration in a VCSEL

NASA Astrophysics Data System (ADS)

Marigo-Lombart, L.; Calvez, S.; Arnoult, A.; Thienpont, H.; Almuneau, G.; Panajotov, K.

2018-04-01

Electro-absorption modulators, either embedded in CMOS technology or integrated with a semiconductor laser, are of high interest for many applications such as optical communications, signal processing and 3D imaging. Recently, the integration of a surface-normal electro-absorption modulator into a vertical-cavity surface-emitting laser has been considered. In this paper we implement a simple quantum well electro-absorption model and design and optimize an asymmetric Fabry-Pérot semiconductor modulator while considering all physical properties within figures of merit. We also extend this model to account for the impact of temperature on the different parameters involved in the calculation of the absorption, such as refractive indices and exciton transition broadening. Two types of vertical modulator structures have been fabricated and experimentally characterized by reflectivity and photocurrent measurements demonstrating a very good agreement with our model. Finally, preliminary results of an electro-absorption modulator vertically integrated with a vertical-cavity surface-emitting laser device are presented, showing good modulation performances required for high speed communications.

Validity of Basic Electronic 1 Module Integrated Character Value Based on Conceptual Change Teaching Model to Increase Students Physics Competency in STKIP PGRI West Sumatera

NASA Astrophysics Data System (ADS)

Hidayati, A.; Rahmi, A.; Yohandri; Ratnawulan

2018-04-01

The importance of teaching materials in accordance with the characteristics of students became the main reason for the development of basic electronics I module integrated character values based on conceptual change teaching model. The module development in this research follows the development procedure of Plomp which includes preliminary research, prototyping phase and assessment phase. In the first year of this research, the module is validated. Content validity is seen from the conformity of the module with the development theory in accordance with the demands of learning model characteristics. The validity of the construct is seen from the linkage and consistency of each module component developed with the characteristic of the integrated learning model of character values obtained through validator assessment. The average validation value assessed by the validator belongs to a very valid category. Based on the validator assessment then revised the basic electronics I module integrated character values based on conceptual change teaching model.

Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study

PubMed Central

2012-01-01

Background The use of biological molecular network information for diagnostic and prognostic purposes and elucidation of molecular disease mechanism is a key objective in systems biomedicine. The network of regulatory miRNA-target and functional protein interactions is a rich source of information to elucidate the function and the prognostic value of miRNAs in cancer. The objective of this study is to identify miRNAs that have high influence on target protein complexes in prostate cancer as a case study. This could provide biomarkers or therapeutic targets relevant for prostate cancer treatment. Results Our findings demonstrate that a miRNA’s functional role can be explained by its target protein connectivity within a physical and functional interaction network. To detect miRNAs with high influence on target protein modules, we integrated miRNA and mRNA expression profiles with a sequence based miRNA-target network and human functional and physical protein interactions (FPI). miRNAs with high influence on target protein complexes play a role in prostate cancer progression and are promising diagnostic or prognostic biomarkers. We uncovered several miRNA-regulated protein modules which were enriched in focal adhesion and prostate cancer genes. Several miRNAs such as miR-96, miR-182, and miR-143 demonstrated high influence on their target protein complexes and could explain most of the gene expression changes in our analyzed prostate cancer data set. Conclusions We describe a novel method to identify active miRNA-target modules relevant to prostate cancer progression and outcome. miRNAs with high influence on protein networks are valuable biomarkers that can be used in clinical investigations for prostate cancer treatment. PMID:22929553

Micro/nanofabricated environments for synthetic biology.

PubMed

Collier, C Patrick; Simpson, Michael L

2011-08-01

A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture

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

Miller, Bradley R.; Drake, Eric J.; Shi, Ce

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived frommore » understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain.« less

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture*

PubMed Central

Miller, Bradley R.; Drake, Eric J.; Shi, Ce; Aldrich, Courtney C.; Gulick, Andrew M.

2016-01-01

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain. PMID:27597544

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture.

PubMed

Miller, Bradley R; Drake, Eric J; Shi, Ce; Aldrich, Courtney C; Gulick, Andrew M

2016-10-21

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Dynamic Neural Networks Supporting Memory Retrieval

PubMed Central

St. Jacques, Peggy L.; Kragel, Philip A.; Rubin, David C.

2011-01-01

How do separate neural networks interact to support complex cognitive processes such as remembrance of the personal past? Autobiographical memory (AM) retrieval recruits a consistent pattern of activation that potentially comprises multiple neural networks. However, it is unclear how such large-scale neural networks interact and are modulated by properties of the memory retrieval process. In the present functional MRI (fMRI) study, we combined independent component analysis (ICA) and dynamic causal modeling (DCM) to understand the neural networks supporting AM retrieval. ICA revealed four task-related components consistent with the previous literature: 1) Medial Prefrontal Cortex (PFC) Network, associated with self-referential processes, 2) Medial Temporal Lobe (MTL) Network, associated with memory, 3) Frontoparietal Network, associated with strategic search, and 4) Cingulooperculum Network, associated with goal maintenance. DCM analysis revealed that the medial PFC network drove activation within the system, consistent with the importance of this network to AM retrieval. Additionally, memory accessibility and recollection uniquely altered connectivity between these neural networks. Recollection modulated the influence of the medial PFC on the MTL network during elaboration, suggesting that greater connectivity among subsystems of the default network supports greater re-experience. In contrast, memory accessibility modulated the influence of frontoparietal and MTL networks on the medial PFC network, suggesting that ease of retrieval involves greater fluency among the multiple networks contributing to AM. These results show the integration between neural networks supporting AM retrieval and the modulation of network connectivity by behavior. PMID:21550407

Integrative modules for efficient genome engineering in yeast

PubMed Central

Amen, Triana; Kaganovich, Daniel

2017-01-01

We present a set of vectors containing integrative modules for efficient genome integration into the commonly used selection marker loci of the yeast Saccharomyces cerevisiae. A fragment for genome integration is generated via PCR with a unique set of short primers and integrated into HIS3, URA3, ADE2, and TRP1 loci. The desired level of expression can be achieved by using constitutive (TEF1p, GPD1p), inducible (CUP1p, GAL1/10p), and daughter-specific (DSE4p) promoters available in the modules. The reduced size of the integrative module compared to conventional integrative plasmids allows efficient integration of multiple fragments. We demonstrate the efficiency of this tool by simultaneously tagging markers of the nucleus, vacuole, actin, and peroxisomes with genomically integrated fluorophores. Improved integration of our new pDK plasmid series allows stable introduction of several genes and can be used for multi-color imaging. New bidirectional promoters (TEF1p-GPD1p, TEF1p-CUP1p, and TEF1p-DSE4p) allow tractable metabolic engineering. PMID:28660202

The modular architecture of protein-protein binding interfaces.

PubMed

Reichmann, D; Rahat, O; Albeck, S; Meged, R; Dym, O; Schreiber, G

2005-01-04

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

Materials-Process Interactions in Ternary Alloy Semiconductors.

DTIC Science & Technology

1984-08-01

high, the surface potential can be * modulated . PECVD SiO. appears to be a viable candidate as a gate dielectric for * Irf ,fO-4A)s MISFETs...it is desirable to integrate the detectors with circuits capable of performing signal processing functions. These circuits can either be fabricated in...to be a major problem in In0. 5 3Ga 0.* 47 s. 25 S. . . . . 13821 -1 R I (a) CROSS SECTION KEYBOARD 210M ANNEALING CHAMBER GATE TRIGG TRIAC

Orientation of Space Station Freedom electrical power system in environmental effects assessment

NASA Technical Reports Server (NTRS)

Lu, Cheng-Yi

1990-01-01

The orientation effects of six Space Station Freedom Electrical Power System (EPS) components are evaluated for three environmental interactions: aerodynamic drag, atomic oxygen erosion, and orbital debris impact. Designers can directly apply these orientation factors to estimate the magnitude of the examined environment and the environmental effects for the EPS component of interest. The six EPS components are the solar array, photovoltaic module radiator, integrated equipment assembly, solar dynamic concentrator, solar dynamic radiator, and beta gimbal.

Polyamines: naturally occurring small molecule modulators of electrostatic protein-protein interactions.

PubMed

Berwanger, Anja; Eyrisch, Susanne; Schuster, Inge; Helms, Volkhard; Bernhardt, Rita

2010-02-01

Modulations of protein-protein interactions are a key step in regulating protein function, especially in networks. Modulators of these interactions are supposed to be candidates for the development of novel drugs. Here, we describe the role of the small, polycationic and highly abundant natural polyamines that could efficiently bind to charged spots at protein interfaces as modulators of such protein-protein interactions. Using the mitochondrial cytochrome P45011A1 (CYP11A1) electron transfer system as a model, we have analyzed the capability of putrescine, spermidine, and spermine at physiologically relevant concentrations to affect the protein-protein interactions between adrenodoxin reductase (AdR), adrenodoxin (Adx), and CYP11A1. The actions of polyamines on the individual components, on their association/dissociation, on electron transfer, and on substrate conversion were examined. These studies revealed modulating effects of polyamines on distinct interactions and on the entire system in a complex way. Modulation via changed protein-protein interactions appeared plausible from docking experiments that suggested favourable high-affinity binding sites of polyamines (spermine>spermidine>putrescine) at the AdR-Adx interface. Our findings imply for the first time that small endogenous compounds are capable of interfering with distinct components of transient protein complexes and might control protein functions by modulating electrostatic protein-protein interactions.

Differential network analysis reveals the genome-wide landscape of estrogen receptor modulation in hormonal cancers

PubMed Central

Hsiao, Tzu-Hung; Chiu, Yu-Chiao; Hsu, Pei-Yin; Lu, Tzu-Pin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Huang, Tim H.-M.; Chuang, Eric Y.; Chen, Yidong

2016-01-01

Several mutual information (MI)-based algorithms have been developed to identify dynamic gene-gene and function-function interactions governed by key modulators (genes, proteins, etc.). Due to intensive computation, however, these methods rely heavily on prior knowledge and are limited in genome-wide analysis. We present the modulated gene/gene set interaction (MAGIC) analysis to systematically identify genome-wide modulation of interaction networks. Based on a novel statistical test employing conjugate Fisher transformations of correlation coefficients, MAGIC features fast computation and adaption to variations of clinical cohorts. In simulated datasets MAGIC achieved greatly improved computation efficiency and overall superior performance than the MI-based method. We applied MAGIC to construct the estrogen receptor (ER) modulated gene and gene set (representing biological function) interaction networks in breast cancer. Several novel interaction hubs and functional interactions were discovered. ER+ dependent interaction between TGFβ and NFκB was further shown to be associated with patient survival. The findings were verified in independent datasets. Using MAGIC, we also assessed the essential roles of ER modulation in another hormonal cancer, ovarian cancer. Overall, MAGIC is a systematic framework for comprehensively identifying and constructing the modulated interaction networks in a whole-genome landscape. MATLAB implementation of MAGIC is available for academic uses at https://github.com/chiuyc/MAGIC. PMID:26972162

Investigating ego modules and pathways in osteosarcoma by integrating the EgoNet algorithm and pathway analysis.

PubMed

Chen, X Y; Chen, Y H; Zhang, L J; Wang, Y; Tong, Z C

2017-02-16

Osteosarcoma (OS) is the most common primary bone malignancy, but current therapies are far from effective for all patients. A better understanding of the pathological mechanism of OS may help to achieve new treatments for this tumor. Hence, the objective of this study was to investigate ego modules and pathways in OS utilizing EgoNet algorithm and pathway-related analysis, and reveal pathological mechanisms underlying OS. The EgoNet algorithm comprises four steps: constructing background protein-protein interaction (PPI) network (PPIN) based on gene expression data and PPI data; extracting differential expression network (DEN) from the background PPIN; identifying ego genes according to topological features of genes in reweighted DEN; and collecting ego modules using module search by ego gene expansion. Consequently, we obtained 5 ego modules (Modules 2, 3, 4, 5, and 6) in total. After applying the permutation test, all presented statistical significance between OS and normal controls. Finally, pathway enrichment analysis combined with Reactome pathway database was performed to investigate pathways, and Fisher's exact test was conducted to capture ego pathways for OS. The ego pathway for Module 2 was CLEC7A/inflammasome pathway, while for Module 3 a tetrasaccharide linker sequence was required for glycosaminoglycan (GAG) synthesis, and for Module 6 was the Rho GTPase cycle. Interestingly, genes in Modules 4 and 5 were enriched in the same pathway, the 2-LTR circle formation. In conclusion, the ego modules and pathways might be potential biomarkers for OS therapeutic index, and give great insight of the molecular mechanism underlying this tumor.

Investigating ego modules and pathways in osteosarcoma by integrating the EgoNet algorithm and pathway analysis

PubMed Central

Chen, X.Y.; Chen, Y.H.; Zhang, L.J.; Wang, Y.; Tong, Z.C.

2017-01-01

Osteosarcoma (OS) is the most common primary bone malignancy, but current therapies are far from effective for all patients. A better understanding of the pathological mechanism of OS may help to achieve new treatments for this tumor. Hence, the objective of this study was to investigate ego modules and pathways in OS utilizing EgoNet algorithm and pathway-related analysis, and reveal pathological mechanisms underlying OS. The EgoNet algorithm comprises four steps: constructing background protein-protein interaction (PPI) network (PPIN) based on gene expression data and PPI data; extracting differential expression network (DEN) from the background PPIN; identifying ego genes according to topological features of genes in reweighted DEN; and collecting ego modules using module search by ego gene expansion. Consequently, we obtained 5 ego modules (Modules 2, 3, 4, 5, and 6) in total. After applying the permutation test, all presented statistical significance between OS and normal controls. Finally, pathway enrichment analysis combined with Reactome pathway database was performed to investigate pathways, and Fisher's exact test was conducted to capture ego pathways for OS. The ego pathway for Module 2 was CLEC7A/inflammasome pathway, while for Module 3 a tetrasaccharide linker sequence was required for glycosaminoglycan (GAG) synthesis, and for Module 6 was the Rho GTPase cycle. Interestingly, genes in Modules 4 and 5 were enriched in the same pathway, the 2-LTR circle formation. In conclusion, the ego modules and pathways might be potential biomarkers for OS therapeutic index, and give great insight of the molecular mechanism underlying this tumor. PMID:28225867

Microarray and network-based identification of functional modules and pathways of active tuberculosis.

PubMed

Bian, Zhong-Rui; Yin, Juan; Sun, Wen; Lin, Dian-Jie

2017-04-01

Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular mechanism of active TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.

PubMed

Umoh, Mfon E; Dammer, Eric B; Dai, Jingting; Duong, Duc M; Lah, James J; Levey, Allan I; Gearing, Marla; Glass, Jonathan D; Seyfried, Nicholas T

2018-01-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Components of cross-frequency modulation in health and disease.

PubMed

Allen, Elena A; Liu, Jingyu; Kiehl, Kent A; Gelernter, Joel; Pearlson, Godfrey D; Perrone-Bizzozero, Nora I; Calhoun, Vince D

2011-01-01

The cognitive deficits associated with schizophrenia are commonly believed to arise from the abnormal temporal integration of information, however a quantitative approach to assess network coordination is lacking. Here, we propose to use cross-frequency modulation (cfM), the dependence of local high-frequency activity on the phase of widespread low-frequency oscillations, as an indicator of network coordination and functional integration. In an exploratory analysis based on pre-existing data, we measured cfM from multi-channel EEG recordings acquired while schizophrenia patients (n = 47) and healthy controls (n = 130) performed an auditory oddball task. Novel application of independent component analysis (ICA) to modulation data delineated components with specific spatial and spectral profiles, the weights of which showed covariation with diagnosis. Global cfM was significantly greater in healthy controls (F(1,175) = 9.25, P < 0.005), while modulation at fronto-temporal electrodes was greater in patients (F(1,175) = 17.5, P < 0.0001). We further found that the weights of schizophrenia-relevant components were associated with genetic polymorphisms at previously identified risk loci. Global cfM decreased with copies of 957C allele in the gene for the dopamine D2 receptor (r = -0.20, P < 0.01) across all subjects. Additionally, greater "aberrant" fronto-temporal modulation in schizophrenia patients was correlated with several polymorphisms in the gene for the α2-subunit of the GABA(A) receptor (GABRA2) as well as the total number of risk alleles in GABRA2 (r = 0.45, P < 0.01). Overall, our results indicate great promise for this approach in establishing patterns of cfM in health and disease and elucidating the roles of oscillatory interactions in functional connectivity.

Audiovisual integration in hemianopia: A neurocomputational account based on cortico-collicular interaction.

PubMed

Magosso, Elisa; Bertini, Caterina; Cuppini, Cristiano; Ursino, Mauro

2016-10-01

Hemianopic patients retain some abilities to integrate audiovisual stimuli in the blind hemifield, showing both modulation of visual perception by auditory stimuli and modulation of auditory perception by visual stimuli. Indeed, conscious detection of a visual target in the blind hemifield can be improved by a spatially coincident auditory stimulus (auditory enhancement of visual detection), while a visual stimulus in the blind hemifield can improve localization of a spatially coincident auditory stimulus (visual enhancement of auditory localization). To gain more insight into the neural mechanisms underlying these two perceptual phenomena, we propose a neural network model including areas of neurons representing the retina, primary visual cortex (V1), extrastriate visual cortex, auditory cortex and the Superior Colliculus (SC). The visual and auditory modalities in the network interact via both direct cortical-cortical connections and subcortical-cortical connections involving the SC; the latter, in particular, integrates visual and auditory information and projects back to the cortices. Hemianopic patients were simulated by unilaterally lesioning V1, and preserving spared islands of V1 tissue within the lesion, to analyze the role of residual V1 neurons in mediating audiovisual integration. The network is able to reproduce the audiovisual phenomena in hemianopic patients, linking perceptions to neural activations, and disentangles the individual contribution of specific neural circuits and areas via sensitivity analyses. The study suggests i) a common key role of SC-cortical connections in mediating the two audiovisual phenomena; ii) a different role of visual cortices in the two phenomena: auditory enhancement of conscious visual detection being conditional on surviving V1 islands, while visual enhancement of auditory localization persisting even after complete V1 damage. The present study may contribute to advance understanding of the audiovisual dialogue between cortical and subcortical structures in healthy and unisensory deficit conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

From Modules to a Generator: An Integrated Heat Exchanger Concept for Car Applications of a Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Bosch, Henry

2016-03-01

A heat exchanger concept for a thermoelectric generator with integrated planar modules for passenger car applications is introduced. The module housings, made of deep drawn stainless steel sheet metal, are brazed onto the exhaust gas channel to achieve an optimal heat transfer on the hot side of the modules. The cooling side consists of winding fluid channels, which are mounted directly onto the cold side of the modules. Only a thin foil separates the cooling media from the modules for an almost direct heat contact on the cooling side. Thermoelectric generators with up to 20 modules made of PbTe and Bi2Te3, respectively, are manufactured and tested on a hot gas generator to investigate electrical power output and performance of the thermoelectric generator. The proof of concept of the light weight heat exchanger design made of sheet metal with integrated modules is positively accomplished.

Molecular dynamics simulations and modelling of the residue interaction networks in the BRAF kinase complexes with small molecule inhibitors: probing the allosteric effects of ligand-induced kinase dimerization and paradoxical activation.

PubMed

Verkhivker, G M

2016-10-20

Protein kinases are central to proper functioning of cellular networks and are an integral part of many signal transduction pathways. The family of protein kinases represents by far the largest and most important class of therapeutic targets in oncology. Dimerization-induced activation has emerged as a common mechanism of allosteric regulation in BRAF kinases, which play an important role in growth factor signalling and human diseases. Recent studies have revealed that most of the BRAF inhibitors can induce dimerization and paradoxically stimulate enzyme transactivation by conferring an active conformation in the second monomer of the kinase dimer. The emerging connections between inhibitor binding and BRAF kinase domain dimerization have suggested a molecular basis of the activation mechanism in which BRAF inhibitors may allosterically modulate the stability of the dimerization interface and affect the organization of residue interaction networks in BRAF kinase dimers. In this work, we integrated structural bioinformatics analysis, molecular dynamics and binding free energy simulations with the protein structure network analysis of the BRAF crystal structures to determine dynamic signatures of BRAF conformations in complexes with different types of inhibitors and probe the mechanisms of the inhibitor-induced dimerization and paradoxical activation. The results of this study highlight previously unexplored relationships between types of BRAF inhibitors, inhibitor-induced changes in the residue interaction networks and allosteric modulation of the kinase activity. This study suggests a mechanism by which BRAF inhibitors could promote or interfere with the paradoxical activation of BRAF kinases, which may be useful in informing discovery efforts to minimize the unanticipated adverse biological consequences of these therapeutic agents.

IAC - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Frisch, H. P.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. With the goal of supporting the unique needs of engineering analysis groups concerned with interdisciplinary problems, IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a data base, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automatic data transfer among analysis programs. IAC 2.5, designed to be compatible as far as possible with Level 1.5, contains a major upgrade in executive and database management system capabilities, and includes interfaces to enable thermal, structures, optics, and control interaction dynamics analysis. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation interfaces are supplied for building and viewing models. Advanced graphics capabilities are provided within particular analysis modules such as INCA and NASTRAN. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files, object code, etc. The user can define groups of data and relations between them. A full data manipulation and query system operates with the database. The current interface modules comprise five groups: 1) Structural analysis - IAC contains a NASTRAN interface for standalone analysis or certain structural/control/thermal combinations. IAC provides enhanced structural capabilities for normal modes and static deformation analysis via special DMAP sequences. IAC 2.5 contains several specialized interfaces from NASTRAN in support of multidisciplinary analysis. 2) Thermal analysis - IAC supports finite element and finite difference techniques for steady state or transient analysis. There are interfaces for the NASTRAN thermal analyzer, SINDA/SINFLO, and TRASYS II. FEMNET, which converts finite element structural analysis models to finite difference thermal analysis models, is also interfaced with the IAC database. 3) System dynamics - The DISCOS simulation program which allows for either nonlinear time domain analysis or linear frequency domain analysis, is fully interfaced to the IAC database management capability. 4) Control analysis - Interfaces for the ORACLS, SAMSAN, NBOD2, and INCA programs allow a wide range of control system analyses and synthesis techniques. Level 2.5 includes EIGEN, which provides tools for large order system eigenanalysis, and BOPACE, which allows for geometric capabilities and finite element analysis with nonlinear material. Also included in IAC level 2.5 is SAMSAN 3.1, an engineering analysis program which contains a general purpose library of over 600 subroutines for numerical analysis. 5) Graphics - The graphics package IPLOT is included in IAC. IPLOT generates vector displays of tabular data in the form of curves, charts, correlation tables, etc. Either DI3000 or PLOT-10 graphics software is required for full graphic capability. In addition to these analysis tools, IAC 2.5 contains an IGES interface which allows the user to read arbitrary IGES files into an IAC database and to edit and output new IGES files. IAC is available by license for a period of 10 years to approved U.S. licensees. The licensed program product includes one set of supporting documentation. Additional copies may be purchased separately. IAC is written in FORTRAN 77 and has been implemented on a DEC VAX series computer operating under VMS. IAC can be executed by multiple concurrent users in batch or interactive mode. The program is structured to allow users to easily delete those program capabilities and "how to" examples they do not want in order to reduce the size of the package. The basic central memory requirement for IAC is approximately 750KB. The following programs are also available from COSMIC as separate packages: NASTRAN, SINDA/SINFLO, TRASYS II, DISCOS, ORACLS, SAMSAN, NBOD2, and INCA. The development of level 2.5 of IAC was completed in 1989.

Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

PubMed Central

Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

2013-01-01

Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602

Coordination in Large Scale Software Development

DTIC Science & Technology

1990-01-01

toward achieving common and explicitly recognized goals" (Blau and Scott, 1962) and "the integration or linking together of different parts of an...require a strong degree of integration of its components. Much software is built of thousands of modules that must mesh with each other perfectly for the...coordination between subgroups producing software modules could lead to failure in integrating the modules themselves. Informal communication. Both

Dynamic speech representations in the human temporal lobe.

PubMed

Leonard, Matthew K; Chang, Edward F

2014-09-01

Speech perception requires rapid integration of acoustic input with context-dependent knowledge. Recent methodological advances have allowed researchers to identify underlying information representations in primary and secondary auditory cortex and to examine how context modulates these representations. We review recent studies that focus on contextual modulations of neural activity in the superior temporal gyrus (STG), a major hub for spectrotemporal encoding. Recent findings suggest a highly interactive flow of information processing through the auditory ventral stream, including influences of higher-level linguistic and metalinguistic knowledge, even within individual areas. Such mechanisms may give rise to more abstract representations, such as those for words. We discuss the importance of characterizing representations of context-dependent and dynamic patterns of neural activity in the approach to speech perception research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1.

PubMed

Bonnard, Carine; Strobl, Anna C; Shboul, Mohammad; Lee, Hane; Merriman, Barry; Nelson, Stanley F; Ababneh, Osama H; Uz, Elif; Güran, Tülay; Kayserili, Hülya; Hamamy, Hanan; Reversade, Bruno

2012-05-13

Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1. We further found that transcriptional control by Irx5 is modulated by direct protein-protein interaction with two GATA zinc-finger proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial transcriptional inputs to regulate key signaling molecules involved in the ontogeny of multiple organs during embryogenesis and homeostasis.

Using Interactive Technology to Support Students' Understanding of the Greenhouse Effect and Global Warming

NASA Astrophysics Data System (ADS)

Varma, Keisha; Linn, Marcia C.

2012-08-01

In this work, we examine middle school students' understanding of the greenhouse effect and global warming. We designed and refined a technology-enhanced curriculum module called Global Warming: Virtual Earth. In the module activities, students conduct virtual experiments with a visualization of the greenhouse effect. They analyze data and draw conclusions about how individual variables effect changes in the Earth's temperature. They also carry out inquiry activities to make connections between scientific processes, the socio-scientific issues, and ideas presented in the media. Results show that participating in the unit increases students' understanding of the science. We discuss how students integrate their ideas about global climate change as a result of using virtual experiments that allow them to explore meaningful complexities of the climate system.

The Interaction between Sytactic and Semantic Modules in Chinese Learners' English Spotaneous Speech

ERIC Educational Resources Information Center

Gang, Xu

2014-01-01

According to modular theory, there are interactive effects between the central modules and language modules. The central cognition may deploy and redeploy resources from language modules. Moreover, the language modules can activate the cognitive ability. So this paper studies the spontaneous speech of students who learn English as a foreign…

Feature confirmation in object perception: Feature integration theory 26 years on from the Treisman Bartlett lecture.

PubMed

Humphreys, Glyn W

2016-10-01

The Treisman Bartlett lecture, reported in the Quarterly Journal of Experimental Psychology in 1988, provided a major overview of the feature integration theory of attention. This has continued to be a dominant account of human visual attention to this day. The current paper provides a summary of the work reported in the lecture and an update on critical aspects of the theory as applied to visual object perception. The paper highlights the emergence of findings that pose significant challenges to the theory and which suggest that revisions are required that allow for (a) several rather than a single form of feature integration, (b) some forms of feature integration to operate preattentively, (c) stored knowledge about single objects and interactions between objects to modulate perceptual integration, (d) the application of feature-based inhibition to object files where visual features are specified, which generates feature-based spreading suppression and scene segmentation, and (e) a role for attention in feature confirmation rather than feature integration in visual selection. A feature confirmation account of attention in object perception is outlined.

Raf Kinase Inhibitory Protein Function Is Regulated via a Flexible Pocket and Novel Phosphorylation-Dependent Mechanism▿ †

PubMed Central

Granovsky, Alexey E.; Clark, Matthew C.; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

2009-01-01

Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics. PMID:19103740

Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.

PubMed

Granovsky, Alexey E; Clark, Matthew C; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

2009-03-01

Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics.

Cooperation and coexpression: How coexpression networks shift in response to multiple mutualists.

PubMed

Palakurty, Sathvik X; Stinchcombe, John R; Afkhami, Michelle E

2018-04-01

A mechanistic understanding of community ecology requires tackling the nonadditive effects of multispecies interactions, a challenge that necessitates integration of ecological and molecular complexity-namely moving beyond pairwise ecological interaction studies and the "gene at a time" approach to mechanism. Here, we investigate the consequences of multispecies mutualisms for the structure and function of genomewide differential coexpression networks for the first time, using the tractable and ecologically important interaction between legume Medicago truncatula, rhizobia and mycorrhizal fungi. First, we found that genes whose expression is affected nonadditively by multiple mutualists are more highly connected in gene networks than expected by chance and had 94% greater network centrality than genes showing additive effects, suggesting that nonadditive genes may be key players in the widespread transcriptomic responses to multispecies symbioses. Second, multispecies mutualisms substantially changed coexpression network structure of 18 modules of host plant genes and 22 modules of the fungal symbionts' genes, indicating that third-party mutualists can cause significant rewiring of plant and fungal molecular networks. Third, we found that 60% of the coexpressed gene sets that explained variation in plant performance had coexpression structures that were altered by interactive effects of rhizobia and fungi. Finally, an "across-symbiosis" approach identified sets of plant and mycorrhizal genes whose coexpression structure was unique to the multiple mutualist context and suggested coupled responses across the plant-mycorrhizal interaction to rhizobial mutualists. Taken together, these results show multispecies mutualisms have substantial effects on the molecular interactions in host plants, microbes and across symbiotic boundaries. © 2018 John Wiley & Sons Ltd.

Tactile cues significantly modulate the perception of sweat-induced skin wetness independently of the level of physical skin wetness

PubMed Central

Fournet, Damien; Hodder, Simon; Havenith, George

2015-01-01

Humans sense the wetness of a wet surface through the somatosensory integration of thermal and tactile inputs generated by the interaction between skin and moisture. However, little is known on how wetness is sensed when moisture is produced via sweating. We tested the hypothesis that, in the absence of skin cooling, intermittent tactile cues, as coded by low-threshold skin mechanoreceptors, modulate the perception of sweat-induced skin wetness, independently of the level of physical wetness. Ten males (22 yr old) performed an incremental exercise protocol during two trials designed to induce the same physical skin wetness but to induce lower (TIGHT-FIT) and higher (LOOSE-FIT) wetness perception. In the TIGHT-FIT, a tight-fitting clothing ensemble limited intermittent skin-sweat-clothing tactile interactions. In the LOOSE-FIT, a loose-fitting ensemble allowed free skin-sweat-clothing interactions. Heart rate, core and skin temperature, galvanic skin conductance (GSC), and physical (wbody) and perceived skin wetness were recorded. Exercise-induced sweat production and physical wetness increased significantly [GSC: 3.1 μS, SD 0.3 to 18.8 μS, SD 1.3, P < 0.01; wbody: 0.26 no-dimension units (nd), SD 0.02, to 0.92 nd, SD 0.01, P < 0.01], with no differences between TIGHT-FIT and LOOSE-FIT (P > 0.05). However, the limited intermittent tactile inputs generated by the TIGHT-FIT ensemble reduced significantly whole-body and regional wetness perception (P < 0.01). This reduction was more pronounced when between 40 and 80% of the body was covered in sweat. We conclude that the central integration of intermittent mechanical interactions between skin, sweat, and clothing, as coded by low-threshold skin mechanoreceptors, significantly contributes to the ability to sense sweat-induced skin wetness. PMID:25878153

Challenging prior evidence for a shared syntactic processor for language and music.

PubMed

Perruchet, Pierre; Poulin-Charronnat, Bénédicte

2013-04-01

A theoretical landmark in the growing literature comparing language and music is the shared syntactic integration resource hypothesis (SSIRH; e.g., Patel, 2008), which posits that the successful processing of linguistic and musical materials relies, at least partially, on the mastery of a common syntactic processor. Supporting the SSIRH, Slevc, Rosenberg, and Patel (Psychonomic Bulletin & Review 16(2):374-381, 2009) recently reported data showing enhanced syntactic garden path effects when the sentences were paired with syntactically unexpected chords, whereas the musical manipulation had no reliable effect on the processing of semantic violations. The present experiment replicated Slevc et al.'s (2009) procedure, except that syntactic garden paths were replaced with semantic garden paths. We observed the very same interactive pattern of results. These findings suggest that the element underpinning interactions is the garden path configuration, rather than the implication of an alleged syntactic module. We suggest that a different amount of attentional resources is recruited to process each type of linguistic manipulations, hence modulating the resources left available for the processing of music and, consequently, the effects of musical violations.

Design of a compact low-power human-computer interaction equipment for hand motion

NASA Astrophysics Data System (ADS)

Wu, Xianwei; Jin, Wenguang

2017-01-01

Human-Computer Interaction (HCI) raises demand of convenience, endurance, responsiveness and naturalness. This paper describes a design of a compact wearable low-power HCI equipment applied to gesture recognition. System combines multi-mode sense signals: the vision sense signal and the motion sense signal, and the equipment is equipped with the depth camera and the motion sensor. The dimension (40 mm × 30 mm) and structure is compact and portable after tight integration. System is built on a module layered framework, which contributes to real-time collection (60 fps), process and transmission via synchronous confusion with asynchronous concurrent collection and wireless Blue 4.0 transmission. To minimize equipment's energy consumption, system makes use of low-power components, managing peripheral state dynamically, switching into idle mode intelligently, pulse-width modulation (PWM) of the NIR LEDs of the depth camera and algorithm optimization by the motion sensor. To test this equipment's function and performance, a gesture recognition algorithm is applied to system. As the result presents, general energy consumption could be as low as 0.5 W.

Perceived images of disability: the reflections of two undergraduate medical students in a university in South Africa on life in a wheelchair.

PubMed

Amosun, Seyi L; Volmink, Lauren; Rosin, Rainer

2005-08-19

The purpose of this manuscript is to document the experiences of two undergraduate medical students at the University of Cape Town, South Africa, who registered for a 4-week special study module titled "Images of Disability", as part of the medical training programme. The objective of the module was to foster the development of positive attitudes toward persons with physical disability through role-playing. The special study module required that the students assumed they had mobility impairments and were physically confined to wheelchairs. The students were required to document their personal experiences of life in a wheelchair for five consecutive working days. The students had to deal with their perceptions of the attitudes of individuals they interacted with, which resulted in feeling of inferiority and lowered self-esteem. The students also identified obstacles in the environment which hindered integration. The students reported significant positive changes in their attitudes towards persons with disabilities.

Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness

PubMed Central

Mashour, George A.; Hudetz, Anthony G.

2017-01-01

There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the “bottom up” paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the “top-down” paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness. PMID:28676745

Tribotronic Tuning Diode for Active Analog Signal Modulation.

PubMed

Zhou, Tao; Yang, Zhi Wei; Pang, Yaokun; Xu, Liang; Zhang, Chi; Wang, Zhong Lin

2017-01-24

Realizing active interaction with external environment/stimuli is a great challenge for current electronics. In this paper, a tribotronic tuning diode (TTD) is proposed by coupling a variable capacitance diode and a triboelectric nanogenerator in free-standing sliding mode. When the friction layer is sliding on the device surface for electrification, a reverse bias voltage is created and applied to the diode for tuning the junction capacitance. When the sliding distance increases from 0 to 25 mm, the capacitance of the TTD decreases from about 39 to 8 pF. The proposed TTD has been integrated into analog circuits and exhibited excellent performances in frequency modulation, phase shift, and filtering by sliding a finger. This work has demonstrated tunable diode and active analog signal modulation by tribotronics, which has great potential to replace ordinary variable capacitance diodes in various practical applications such as signal processing, electronic tuning circuits, precise tuning circuits, active sensor networks, electronic communications, remote controls, flexible electronics, etc.

Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness.

PubMed

Mashour, George A; Hudetz, Anthony G

2017-01-01

There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the "bottom up" paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the "top-down" paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness.

Pausing kinetics dominates strand-displacement polymerization by reverse transcriptase

PubMed Central

Malik, Omri; Khamis, Hadeel; Rudnizky, Sergei; Marx, Ailie

2017-01-01

Abstract Reverse transcriptase (RT) catalyzes the conversion of the viral RNA into an integration-competent double-stranded DNA, with a variety of enzymatic activities that include the ability to displace a non-template strand concomitantly with polymerization. Here, using high-resolution optical tweezers to follow the activity of the murine leukemia Virus RT, we show that strand-displacement polymerization is frequently interrupted. Abundant pauses are modulated by the strength of the DNA duplex ∼8 bp ahead, indicating the existence of uncharacterized RT/DNA interactions, and correspond to backtracking of the enzyme, whose recovery is also modulated by the duplex strength. Dissociation and reinitiation events, which induce long periods of inactivity and are likely the rate-limiting step in the synthesis of the genome in vivo, are modulated by the template structure and the viral nucleocapsid protein. Our results emphasize the potential regulatory role of conserved structural motifs, and may provide useful information for the development of potent and specific inhibitors. PMID:28973474

Neuropeptide Substance P and the Immune Response

PubMed Central

Tehrani, Mohsen; Grace, Peter M.; Pothoulakis, Charalabos; Dana, Reza

2016-01-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response. PMID:27314883

Neuropeptide substance P and the immune response.

PubMed

Mashaghi, Alireza; Marmalidou, Anna; Tehrani, Mohsen; Grace, Peter M; Pothoulakis, Charalabos; Dana, Reza

2016-11-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.

Nipple pain associated with breastfeeding: incorporating current neurophysiology into clinical reasoning.

PubMed

Amir, Lisa H; Jones, Lester E; Buck, Miranda L

2015-03-01

New mothers frequently experience breastfeeding problems, in particular nipple pain. This is often attributed to compression, skin damage, infection or dermatitis. To outline an integrated approach to breastfeeding pain assessment that seeks to enhance current practice. Our clinical reasoning model resolves the complexity of pain into three categories: local stimulation, external influences and central modulation. Tissue pathology, damage or inflammation leads to local stimulation of nociceptors. External influences such as creams and breast pumps, as well as factors related to the mother, the infant and the maternal-infant interaction, may exacerbate the pain. Central nervous system modulation includes the enhancement of nociceptive transmission at the spinal cord and modification of the descending inhibitory influences. A broad range of factors can modulate pain through central mechanisms including maternal illness, exhaustion, lack of support, anxiety, depression or history of abuse. General practitioners (GPs) can use this model to explain nipple pain in complex settings, thus increasing management options for women.

Dynamic interactions between cells and their extracellular matrix mediate embryonic development.

PubMed

Goody, Michelle F; Henry, Clarissa A

2010-06-01

Cells and their surrounding extracellular matrix microenvironment interact throughout all stages of life. Understanding the continuously changing scope of cell-matrix interactions in vivo is crucial to garner insights into both congenital birth defects and disease progression. A current challenge in the field of developmental biology is to adapt in vitro tools and rapidly evolving imaging technology to study cell-matrix interactions in a complex 4-D environment. In this review, we highlight the dynamic modulation of cell-matrix interactions during development. We propose that individual cell-matrix adhesion proteins are best considered as complex proteins that can play multiple, often seemingly contradictory roles, depending upon the context of the microenvironment. In addition, cell-matrix proteins can also exert different short versus long term effects. It is thus important to consider cell behavior in light of the microenvironment because of the constant and dynamic reciprocal interactions occurring between them. Finally, we suggest that analysis of cell-matrix interactions at multiple levels (molecules, cells, tissues) in vivo is critical for an integrated understanding because different information can be acquired from all size scales. Copyright 2010 Wiley-Liss, Inc.

The functional integration of the anterior cingulate cortex during conflict processing.

PubMed

Fan, Jin; Hof, Patrick R; Guise, Kevin G; Fossella, John A; Posner, Michael I

2008-04-01

Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.

VMS-ROT: A New Module of the Virtual Multifrequency Spectrometer for Simulation, Interpretation, and Fitting of Rotational Spectra

PubMed Central

2017-01-01

The Virtual Multifrequency Spectrometer (VMS) is a tool that aims at integrating a wide range of computational and experimental spectroscopic techniques with the final goal of disclosing the static and dynamic physical–chemical properties “hidden” in molecular spectra. VMS is composed of two parts, namely, VMS-Comp, which provides access to the latest developments in the field of computational spectroscopy, and VMS-Draw, which provides a powerful graphical user interface (GUI) for an intuitive interpretation of theoretical outcomes and a direct comparison to experiment. In the present work, we introduce VMS-ROT, a new module of VMS that has been specifically designed to deal with rotational spectroscopy. This module offers an integrated environment for the analysis of rotational spectra: from the assignment of spectral transitions to the refinement of spectroscopic parameters and the simulation of the spectrum. While bridging theoretical and experimental rotational spectroscopy, VMS-ROT is strongly integrated with quantum-chemical calculations, and it is composed of four independent, yet interacting units: (1) the computational engine for the calculation of the spectroscopic parameters that are employed as a starting point for guiding experiments and for the spectral interpretation, (2) the fitting-prediction engine for the refinement of the molecular parameters on the basis of the assigned transitions and the prediction of the rotational spectrum of the target molecule, (3) the GUI module that offers a powerful set of tools for a vis-à-vis comparison between experimental and simulated spectra, and (4) the new assignment tool for the assignment of experimental transitions in terms of quantum numbers upon comparison with the simulated ones. The implementation and the main features of VMS-ROT are presented, and the software is validated by means of selected test cases ranging from isolated molecules of different sizes to molecular complexes. VMS-ROT therefore offers an integrated environment for the analysis of the rotational spectra, with the innovative perspective of an intimate connection to quantum-chemical calculations that can be exploited at different levels of refinement, as an invaluable support and complement for experimental studies. PMID:28742339

BiologicalNetworks 2.0 - an integrative view of genome biology data

PubMed Central

2010-01-01

Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other) and their relations (interactions, co-expression, co-citations, and other). The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org. PMID:21190573

The selective digital integrator: A new device for modulated polarization spectroscopy

NASA Astrophysics Data System (ADS)

Vrancic, Aljosa

1998-12-01

A new device, a selective digital integrator (SDI), for the acquisition of modulated polarization spectroscopy (MPS) signals is described. Special attention is given to the accurate measurement of very small (AC component of interest <10-3 x DC component), rapidly modulated (~50 kHz) signals at or below noise levels. Various data acquisition methods and problems associated with the collection of modulated signals are discussed. The SDI solves most of these problems and has the following advantages: it provides the average-time resolved profile of a modulated signal; it eliminates errors if the modulation is not sinusoidal; it enables separate measurements of the various phases of the signal modulation cycle; it permits simultaneous measurement of absorption, circular dichroism (CD) and linear dichroism (LD) spectra; it facilitates 3-D absorbance measurements; it has a wide gain-switching-free dynamic range (10 orders of magnitude or more); it offers a constant S/N ratio mode of operation; it eliminates the need for photomultiplier voltage feedback, and it has faster scanning speeds. The time-resolution, selectivity, wide dynamic range, and low-overhead on-the-fly data processing are useful for other modulated spectroscopy (MS) and non-MS experiments such as pulse height distribution and time-resolved pulse counting measurements. The advantages of the MPS-SDI method are tested on the first Rydberg electronic transitions of (+)-3- methylcyclopentanone. The experimental results validate the predicted SDI capabilities. However, they also point to two difficulties that had not been noted previously: the presence of LD in a gaseous sample and a pressure- dependence of the relative peak heights of the CD spectrum. Models for these anomalies are proposed. The presence of the oscillatory LD (but not an LD background) is explained with a sample cell model based on the observed polarization-dependent time-resolved profiles of transmitted light intensity. To obtain expressions for these intensities, a theoretical background, which provides a new approach to the treatment of light/matter interaction, is included as an Appendix. To explain the second anomaly, present only at high optical densities, a model based on the presence of scattered light is introduced and verified. The mode of correction for the scattering problem is outlined.

Integrating Learning Styles and Personality Traits into an Affective Model to Support Learner's Learning

NASA Astrophysics Data System (ADS)

Leontidis, Makis; Halatsis, Constantin

The aim of this paper is to present a model in order to integrate the learning style and the personality traits of a learner into an enhanced Affective Style which is stored in the learner’s model. This model which can deal with the cognitive abilities as well as the affective preferences of the learner is called Learner Affective Model (LAM). The LAM is used to retain learner’s knowledge and activities during his interaction with a Web-based learning environment and also to provide him with the appropriate pedagogical guidance. The proposed model makes use of an ontological approach in combination with the Bayesian Network model and contributes to the efficient management of the LAM in an Affective Module.

Empathy-Related Responses to Depicted People in Art Works

PubMed Central

Kesner, Ladislav; Horáček, Jiří

2017-01-01

Existing theories of empathic response to visual art works postulate the primacy of automatic embodied reaction to images based on mirror neuron mechanisms. Arguing for a more inclusive concept of empathy-related response and integrating four distinct bodies of literature, we discuss contextual, and personal factors which modulate empathic response to depicted people. We then present an integrative model of empathy-related responses to depicted people in art works. The model assumes that a response to empathy-eliciting figural artworks engages the dynamic interaction of two mutually interlinked sets of processes: socio-affective/cognitive processing, related to the person perception, and esthetic processing, primarily concerned with esthetic appreciation and judgment and attention to non-social aspects of the image. The model predicts that the specific pattern of interaction between empathy-related and esthetic processing is co-determined by several sets of factors: (i) the viewer's individual characteristics, (ii) the context variables (which include various modes of priming by narratives and other images), (iii) multidimensional features of the image, and (iv) aspects of a viewer's response. Finally we propose that the model is implemented by the interaction of functionally connected brain networks involved in socio-cognitive and esthetic processing. PMID:28286487

Orientation is different: Interaction between contour integration and feature contrasts in visual search.

PubMed

Jingling, Li; Tseng, Chia-Huei; Zhaoping, Li

2013-09-10

Salient items usually capture attention and are beneficial to visual search. Jingling and Tseng (2013), nevertheless, have discovered that a salient collinear column can impair local visual search. The display used in that study had 21 rows and 27 columns of bars, all uniformly horizontal (or vertical) except for one column of bars orthogonally oriented to all other bars, making this unique column of collinear (or noncollinear) bars salient in the display. Observers discriminated an oblique target bar superimposed on one of the bars either in the salient column or in the background. Interestingly, responses were slower for a target in a salient collinear column than in the background. This opens a theoretical question of how contour integration interacts with salience computation, which is addressed here by an examination of how salience modulated the search impairment from the collinear column. We show that the collinear column needs to have a high orientation contrast with its neighbors to exert search interference. A collinear column of high contrast in color or luminance did not produce the same impairment. Our results show that orientation-defined salience interacted with collinear contour differently from other feature dimensions, which is consistent with the neuronal properties in V1.

Integrated optical signal processing with magnetostatic waves

NASA Technical Reports Server (NTRS)

Fisher, A. D.; Lee, J. N.

1984-01-01

Magneto-optical devices based on Bragg diffraction of light by magnetostatic waves (MSW's) offer the potential of large time-bandwidth optical signal processing at microwave frequencies of 1 to 20 GHz and higher. A thin-film integrated-optical configuration, with the interacting MSW and guided-optical wave both propagating in a common ferrite layer, is necessary to avoid shape-factor demagnetization effects. The underlying theory of the MSW-optical interaction is outlined, including the development of expressions for optical diffraction efficiency as a function of MSW power and other relevant parameters. Bradd diffraction of guided-optical waves by transversely-propagating magnetostatic waves and collinear TE/TM mode conversion included by MSW's have been demonstrated in yttrium iron garnet (YIG) thin films. Diffraction levels as large as 4% (7 mm interaction length) and a modulation dynamic range of approx 30 dB have been observed. Advantages of these MSW-based devices over the analogous acousto-optical devices include: much greater operating frequencies, tunability of the MSW dispersion relation by varying either the RF frequency or the applied bias magnetic field, simple broad-band MSW transducer structures (e.g., a single stripline), and the potential for very high diffraction efficiencies.

Monolithically integrated InGaAsP/InP laser/modulator using identical layer approach for opto-electronic oscillator

NASA Astrophysics Data System (ADS)

Wu, Chi; Keo, Sam A.; Yao, X. S.; Turner, Tasha E.; Davis, Lawrence J.; Young, Martin G.; Maleki, Lute; Forouhar, Siamak

1998-08-01

The microwave optoelectronic oscillator (OEO) has been demonstrated on a breadboard. The future trend is to integrate the whole OEO on a chip, which requires the development of high power and high efficiency integrated photonic components. In this paper, we will present the design and fabrication of an integrated semiconductor laser/modulator using the identical active layer approach on InGaAsP/InP material. The best devices have threshold currents of 50-mA at room temperature for CW operation. The device length is approximately 3-mm, resulting in a mode spacing of 14 GHz. For only 5-dBm microwave power applied to the modulator section, modulation response with 30 dB resonate enhancement has been observed. This work shows the promise for an on-chip integrated OEO.

Content congruency and its interplay with temporal synchrony modulate integration between rhythmic audiovisual streams.

PubMed

Su, Yi-Huang

2014-01-01

Both lower-level stimulus factors (e.g., temporal proximity) and higher-level cognitive factors (e.g., content congruency) are known to influence multisensory integration. The former can direct attention in a converging manner, and the latter can indicate whether information from the two modalities belongs together. The present research investigated whether and how these two factors interacted in the perception of rhythmic, audiovisual (AV) streams derived from a human movement scenario. Congruency here was based on sensorimotor correspondence pertaining to rhythm perception. Participants attended to bimodal stimuli consisting of a humanlike figure moving regularly to a sequence of auditory beat, and detected a possible auditory temporal deviant. The figure moved either downwards (congruently) or upwards (incongruently) to the downbeat, while in both situations the movement was either synchronous with the beat, or lagging behind it. Greater cross-modal binding was expected to hinder deviant detection. Results revealed poorer detection for congruent than for incongruent streams, suggesting stronger integration in the former. False alarms increased in asynchronous stimuli only for congruent streams, indicating greater tendency for deviant report due to visual capture of asynchronous auditory events. In addition, a greater increase in perceived synchrony was associated with a greater reduction in false alarms for congruent streams, while the pattern was reversed for incongruent ones. These results demonstrate that content congruency as a top-down factor not only promotes integration, but also modulates bottom-up effects of synchrony. Results are also discussed regarding how theories of integration and attentional entrainment may be combined in the context of rhythmic multisensory stimuli.

In situ targeting TEM8 via immune response and polypeptide recognition by wavelength-modulated surface plasmon resonance biosensor

PubMed Central

Wang, Yimin; Luo, Zewei; Liu, Kunping; Wang, Jie; Duan, Yixiang

2016-01-01

There is an increasing interest in real-time and in situ monitoring of living cell activities in life science and medicine. This paper reports a whole cell sensing protocol over the interface of Au film coupled in a wavelength-modulated surface plasmon resonance (WMSPR) biosensor. With dual parabolic mirrors integrated in the sensor, the compact and miniaturized instrument shows satisfactory refractive index sensitivity (2220 nm/RIU) and a high resolution of resonance wavelength shift of 0.3 nm to liquid samples. The affinity interactions between the biomarker of human tumor endothelial marker 8 (TEM8) and antibody (Ab) or specific polypeptide (PEP) were firstly introduced to WMSPR biosensor analysis. Both the interaction events of Ab-cell and PEP-cell over the Au film interface can be recognized by the sensor and the balance time of interactions is about 20 min. The concentration range of Ab for quantitative monitoring of the TEM8 expression on human colon carcinoma SW620 cells was investigated. The present low-cost and time-saving method provides a time resolution of binding specificity between Ab/PEP and TEM8 for real-time analysis of antigen on living tumor cell surface. PMID:26822761

Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain

PubMed Central

Wojtaszek, Jessica L.; Wang, Su; Kim, Hyungjin; Wu, Qinglin; D'Andrea, Alan D.; Zhou, Pei

2014-01-01

FAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ–ubiquitin interaction is thought to be exclusively encapsulated within the ββα module of UBZ, we show that the FAAP20–ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended β-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44Ub for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20–ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair. PMID:25414354

An Integrated Teaching Module.

ERIC Educational Resources Information Center

Samuel, Marie R.; Seiferth, Berniece B.

This integrated teaching module provides elementary and junior high school teachers with a "hands-on" approach to studying the Anasazi Indian. Emphasis is on creative exploration that focuses on integrating art, music, poetry, writing, geography, dance, history, anthropology, sociology, and archaeology. Replicas of artifacts,…

Systematic pan-cancer analysis reveals immune cell interactions in the tumor microenvironment

PubMed Central

Varn, Frederick S.; Wang, Yue; Mullins, David W.; Fiering, Steven; Cheng, Chao

2017-01-01

With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multi-dimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we inferred the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a co-infiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we found that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors likely explained differences between tumors originating from the same tissue. We concluded this analysis by examining the prognostic value of individual immune cell subsets as well as how co-infiltration of functionally discordant cell types associated with patient survival. In multiple tumor types, we found that the protective effect of CD8+ T cell infiltration was heavily modulated by co-infiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response. PMID:28126714

Wide-band analog frequency modulation of optic signals using indirect techniques

NASA Technical Reports Server (NTRS)

Fitzmartin, D. J.; Balboni, E. J.; Gels, R. G.

1991-01-01

The wideband frequency modulation (FM) of an optical carrier by a radio frequency (RF) or microwave signal can be accomplished independent of laser type when indirect modulation is employed. Indirect modulators exploit the integral relation of phase to frequency so that phase modulators can be used to impress frequency modulation on an optical carrier. The use of integrated optics phase modulators, which are highly linear, enables the generation of optical wideband FM signals with very low intermodulation distortion. This modulator can be used as part of an optical wideband FM link for RF and microwave signals. Experimental results from the test of an indirect frequency modulator for an optical carrier are discussed.

New insights into the interplay between the lysine transporter LysP and the pH sensor CadC in Escherichia coli.

PubMed

Rauschmeier, Martina; Schüppel, Valentina; Tetsch, Larissa; Jung, Kirsten

2014-01-09

The coordination of signal transduction and substrate transport represents a sophisticated way to integrate information on metabolite fluxes into transcriptional regulation. This widely distributed process involves protein-protein interactions between two integral membrane proteins. Here we report new insights into the molecular mechanism of the regulatory interplay between the lysine-specific permease LysP and the membrane-integrated pH sensor CadC, which together induce lysine-dependent adaptation of E. coli under acidic stress. In vivo analyses revealed that, in the absence of either stimulus, the two proteins form a stable association, which is modulated by lysine and low pH. In addition to its transmembrane helix, the periplasmic domain of CadC also participated in the interaction. Site-directed mutagenesis pinpointed Arg265 and Arg268 in CadC as well as Asp275 and Asp278 in LysP as potential periplasmic interaction sites. Moreover, a systematic analysis of 100 LysP variants with single-site replacements indicated that the lysine signal is transduced from co-sensor to sensor via lysine-dependent conformational changes (upon substrate binding and/or transport) of LysP. Our results suggest a scenario in which CadC is inhibited by LysP via intramembrane and periplasmic contacts under non-inducing conditions. Upon induction, lysine-dependent conformational changes in LysP transduce the lysine signal via a direct conformational coupling to CadC without resolving the interaction completely. Moreover, concomitant pH-dependent protonation of periplasmic amino acids in both proteins dissolves their electrostatic connections resulting in further destabilization of the CadC/LysP interaction. © 2013.

Development of an integrated model for the Campaspe catchment: a tool to help improve understanding of the interaction between society, policy, farming decision, ecology, hydrology and climate

NASA Astrophysics Data System (ADS)

Iwanaga, Takuya; Zare, Fateme; Croke, Barry; Fu, Baihua; Merritt, Wendy; Partington, Daniel; Ticehurst, Jenifer; Jakeman, Anthony

2018-06-01

Management of water resources requires understanding of the hydrology and hydrogeology, as well as the policy and human drivers and their impacts. This understanding requires relevant inputs from a wide range of disciplines, which will vary depending on the specific case study. One approach to gain understanding of the impact of climate and society on water resources is through the use of an integrated modelling process that engages stakeholders and experts in specifics of problem framing, co-design of the underpinning conceptual model, and discussion of the ensuing results. In this study, we have developed such an integrated modelling process for the Campaspe basin in northern Victoria, Australia. The numerical model built has a number of components:

• - Node/link based surface water hydrology module based on the IHACRES rainfall-streamflow model
• - Distributed groundwater model for the lower catchment (MODFLOW)
• - Farm decision optimisation module (to determine irrigation requirements)
• - Policy module (setting conditions on availability of water based on existing rules)
• - Ecology module (determining the impacts of available streamflow on platypus, fish and river red gum trees)

Interharmonic modulation products as a means to quantify nonlinear D-region interactions

NASA Astrophysics Data System (ADS)

Moore, Robert

Experimental observations performed during dual beam ionospheric HF heating experiments at the High frequency Active Auroral Research Program (HAARP) HF transmitter in Gakona, Alaska are used to quantify the relative importance of specific nonlinear interactions that occur within the D region ionosphere. During these experiments, HAARP broadcast two amplitude modulated HF beams whose center frequencies were separated by less than 20 kHz. One beam was sinusoidally modulated at 500 Hz while the second beam was sinusoidally modulated using a 1-7 kHz linear frequency-time chirp. ELF/VLF observations performed at two different locations (3 and 98 km from HAARP) provide clear evidence of strong interactions between all field components of the two HF beams in the form of low and high order interharmonic modulation products. From a theoretical standpoint, the observed interharmonic modulation products could be produced by several different nonlinearities. The two primary nonlinearities take the form of wave-medium interactions (i.e., cross modulation), wherein the ionospheric conductivity modulation produced by one signal crosses onto the other signal via collision frequency modification, and wave-wave interactions, wherein the conduction current associated with one wave mixes with the electric field of the other wave to produce electron temperature oscillations. We are able to separate and quantify these two different nonlinearities, and we conclude that the wave-wave interactions dominate the wave-medium interactions by a factor of two. These results are of great importance for the modeling of transioinospheric radio wave propagation, in that both the wave-wave and the wave-medium interactions could be responsible for a significant amount of anomalous absorption.

A simple integrated assessment approach to global change simulation and evaluation

NASA Astrophysics Data System (ADS)

Ogutu, Keroboto; D'Andrea, Fabio; Ghil, Michael

2016-04-01

We formulate and study the Coupled Climate-Economy-Biosphere (CoCEB) model, which constitutes the basis of our idealized integrated assessment approach to simulating and evaluating global change. CoCEB is composed of a physical climate module, based on Earth's energy balance, and an economy module that uses endogenous economic growth with physical and human capital accumulation. A biosphere model is likewise under study and will be coupled to the existing two modules. We concentrate on the interactions between the two subsystems: the effect of climate on the economy, via damage functions, and the effect of the economy on climate, via a control of the greenhouse gas emissions. Simple functional forms of the relation between the two subsystems permit simple interpretations of the coupled effects. The CoCEB model is used to make hypotheses on the long-term effect of investment in emission abatement, and on the comparative efficacy of different approaches to abatement, in particular by investing in low carbon technology, in deforestation reduction or in carbon capture and storage (CCS). The CoCEB model is very flexible and transparent, and it allows one to easily formulate and compare different functional representations of climate change mitigation policies. Using different mitigation measures and their cost estimates, as found in the literature, one is able to compare these measures in a coherent way.

Estrogenic encounters: How interactions between aromatase and the environment modulate aggression

PubMed Central

Trainor, Brian C.; Kyomen, Helen H.; Marler, Catherine A.

2007-01-01

Initial investigations into the mechanistic basis of aggression focused on the role of testosterone (T) and a variety of studies on non-human animals found that elevated T levels promote aggression. However, many correlational studies have not detected a significant association between aggression and peripheral T levels. One reason for this inconsistency may be due to differential metabolism of T within the brain, in particular, the conversion of T to estrogen by aromatase. Thus, differences in aromatase enzyme activity, estrogen receptor expression, and related cofactors may have important effects on how steroids affect aggressive behavior. Hormone manipulation studies conducted in a wide variety of species indicate that estrogens modulate aggression. There is also growing evidence that social experience has important effects on the production of estrogen within the brain, and some cases can not be explained by androgenic regulation of aromatase. Such changes in central aromatase activity may play an important role in determining how social experiences affect the probability of whether an individual engages in aggressive behavior. Although studies have been conducted in many taxa, there has been relatively little integration between literatures examining aggression in different species. In this review, we compare and contrast studies examining aggression in birds, mammals, and humans. By taking an integrative approach to our review, we consider mechanisms that could explain species differences in how estrogen modulates aggression. PMID:16376420

ISLE (Image and Signal Processing LISP Environment) reference manual

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

Sherwood, R.J.; Searfus, R.M.

1990-01-01

ISLE is a rapid prototyping system for performing image and signal processing. It is designed to meet the needs of a person doing development of image and signal processing algorithms in a research environment. The image and signal processing modules in ISLE form a very capable package in themselves. They also provide a rich environment for quickly and easily integrating user-written software modules into the package. ISLE is well suited to applications in which there is a need to develop a processing algorithm in an interactive manner. It is straightforward to develop the algorithms, load it into ISLE, apply themore » algorithm to an image or signal, display the results, then modify the algorithm and repeat the develop-load-apply-display cycle. ISLE consists of a collection of image and signal processing modules integrated into a cohesive package through a standard command interpreter. ISLE developer elected to concentrate their effort on developing image and signal processing software rather than developing a command interpreter. A COMMON LISP interpreter was selected for the command interpreter because it already has the features desired in a command interpreter, it supports dynamic loading of modules for customization purposes, it supports run-time parameter and argument type checking, it is very well documented, and it is a commercially supported product. This manual is intended to be a reference manual for the ISLE functions The functions are grouped into a number of categories and briefly discussed in the Function Summary chapter. The full descriptions of the functions and all their arguments are given in the Function Descriptions chapter. 6 refs.« less

Development of an Integrated Hydrologic Modeling System for Rainfall-Runoff Simulation

NASA Astrophysics Data System (ADS)

Lu, B.; Piasecki, M.

2008-12-01

This paper aims to present the development of an integrated hydrological model which involves functionalities of digital watershed processing, online data retrieval, hydrologic simulation and post-event analysis. The proposed system is intended to work as a back end to the CUAHSI HIS cyberinfrastructure developments. As a first step into developing this system, a physics-based distributed hydrologic model PIHM (Penn State Integrated Hydrologic Model) is wrapped into OpenMI(Open Modeling Interface and Environment ) environment so as to seamlessly interact with OpenMI compliant meteorological models. The graphical user interface is being developed from the openGIS application called MapWindows which permits functionality expansion through the addition of plug-ins. . Modules required to set up through the GUI workboard include those for retrieving meteorological data from existing database or meteorological prediction models, obtaining geospatial data from the output of digital watershed processing, and importing initial condition and boundary condition. They are connected to the OpenMI compliant PIHM to simulate rainfall-runoff processes and includes a module for automatically displaying output after the simulation. Online databases are accessed through the WaterOneFlow web services, and the retrieved data are either stored in an observation database(OD) following the schema of Observation Data Model(ODM) in case for time series support, or a grid based storage facility which may be a format like netCDF or a grid-based-data database schema . Specific development steps include the creation of a bridge to overcome interoperability issue between PIHM and the ODM, as well as the embedding of TauDEM (Terrain Analysis Using Digital Elevation Models) into the model. This module is responsible for developing watershed and stream network using digital elevation models. Visualizing and editing geospatial data is achieved by the usage of MapWinGIS, an ActiveX control developed by MapWindow team. After applying to the practical watershed, the performance of the model can be tested by the post-event analysis module.

Fundamental concepts of integrated and fiber optic sensors

NASA Technical Reports Server (NTRS)

Tuma, Margaret L.

1995-01-01

This chapter discusses fiber optic and integrated optic sensor concepts. Unfortunately, there is no standard method to categorize these sensor concepts. Here, fiber optic and integrated optic sensor concepts will be categorized by the primary modulation technique. These modulation techniques have been classified as: intensity, phase, wavelength, polarization, and time/frequency modulation. All modulate the output light with respect to changes in the physical or chemical property to be measured. Each primary modulation technique is then divided into fiber optic and integrated optic sections which are treated independently. For each sensor concept, possible sensor applications are discussed. The sensors and references discussed are not exhaustive, but sufficient to give the reader an overview of sensor concepts developed to date. Sensor multiplexing techniques such as wavelength division, time division, and frequency division will not be discussed as they are beyond the scope of this report.

miREE: miRNA recognition elements ensemble

PubMed Central

2011-01-01

Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/ PMID:22115078

The Impact of Interactive, Computerized Educational Modules on Preclinical Medical Education

ERIC Educational Resources Information Center

Bryner, Benjamin S.; Saddawi-Konefka, Daniel; Gest, Thomas R.

2008-01-01

Interactive computerized modules have been linked to improved retention of material in clinical medicine. This study examined the effects of a new series of interactive learning modules for preclinical medical education, specifically in the areas of quiz performance, perceived difficulty of concepts, study time, and perceived stress level. We…

Energy Conservation Curriculum for Secondary and Post-Secondary Students. Module 1: Awareness of the Energy Dilemma.

ERIC Educational Resources Information Center

Navarro Coll., Corsicana, TX.

This module is the first in a series of eleven modules in an energy conservation curriculum for secondary and postsecondary vocational students. It is designed for use by itself, to be integrated with the other ten modules into a program on energy conservation, or to be integrated into conventional vocational courses as a unit of instruction. The…

Design and Development of ChemInfoCloud: An Integrated Cloud Enabled Platform for Virtual Screening.

PubMed

Karthikeyan, Muthukumarasamy; Pandit, Deepak; Bhavasar, Arvind; Vyas, Renu

2015-01-01

The power of cloud computing and distributed computing has been harnessed to handle vast and heterogeneous data required to be processed in any virtual screening protocol. A cloud computing platorm ChemInfoCloud was built and integrated with several chemoinformatics and bioinformatics tools. The robust engine performs the core chemoinformatics tasks of lead generation, lead optimisation and property prediction in a fast and efficient manner. It has also been provided with some of the bioinformatics functionalities including sequence alignment, active site pose prediction and protein ligand docking. Text mining, NMR chemical shift (1H, 13C) prediction and reaction fingerprint generation modules for efficient lead discovery are also implemented in this platform. We have developed an integrated problem solving cloud environment for virtual screening studies that also provides workflow management, better usability and interaction with end users using container based virtualization, OpenVz.

High-frequency Born synthetic seismograms based on coupled normal modes

USGS Publications Warehouse

Pollitz, Fred F.

2011-01-01

High-frequency and full waveform synthetic seismograms on a 3-D laterally heterogeneous earth model are simulated using the theory of coupled normal modes. The set of coupled integral equations that describe the 3-D response are simplified into a set of uncoupled integral equations by using the Born approximation to calculate scattered wavefields and the pure-path approximation to modulate the phase of incident and scattered wavefields. This depends upon a decomposition of the aspherical structure into smooth and rough components. The uncoupled integral equations are discretized and solved in the frequency domain, and time domain results are obtained by inverse Fourier transform. Examples show the utility of the normal mode approach to synthesize the seismic wavefields resulting from interaction with a combination of rough and smooth structural heterogeneities. This approach is applied to an ∼4 Hz shallow crustal wave propagation around the site of the San Andreas Fault Observatory at Depth (SAFOD).

The Design of Modular Web-Based Collaboration

NASA Astrophysics Data System (ADS)

Intapong, Ploypailin; Settapat, Sittapong; Kaewkamnerdpong, Boonserm; Achalakul, Tiranee

Online collaborative systems are popular communication channels as the systems allow people from various disciplines to interact and collaborate with ease. The systems provide communication tools and services that can be integrated on the web; consequently, the systems are more convenient to use and easier to install. Nevertheless, most of the currently available systems are designed according to some specific requirements and cannot be straightforwardly integrated into various applications. This paper provides the design of a new collaborative platform, which is component-based and re-configurable. The platform is called the Modular Web-based Collaboration (MWC). MWC shares the same concept as computer supported collaborative work (CSCW) and computer-supported collaborative learning (CSCL), but it provides configurable tools for online collaboration. Each tool module can be integrated into users' web applications freely and easily. This makes collaborative system flexible, adaptable and suitable for online collaboration.

Statistics of extreme waves in the framework of one-dimensional Nonlinear Schrodinger Equation

NASA Astrophysics Data System (ADS)

Agafontsev, Dmitry; Zakharov, Vladimir

2013-04-01

We examine the statistics of extreme waves for one-dimensional classical focusing Nonlinear Schrodinger (NLS) equation, iΨt + Ψxx + |Ψ |2Ψ = 0, (1) as well as the influence of the first nonlinear term beyond Eq. (1) - the six-wave interactions - on the statistics of waves in the framework of generalized NLS equation accounting for six-wave interactions, dumping (linear dissipation, two- and three-photon absorption) and pumping terms, We solve these equations numerically in the box with periodically boundary conditions starting from the initial data Ψt=0 = F(x) + ?(x), where F(x) is an exact modulationally unstable solution of Eq. (1) seeded by stochastic noise ?(x) with fixed statistical properties. We examine two types of initial conditions F(x): (a) condensate state F(x) = 1 for Eq. (1)-(2) and (b) cnoidal wave for Eq. (1). The development of modulation instability in Eq. (1)-(2) leads to formation of one-dimensional wave turbulence. In the integrable case the turbulence is called integrable and relaxes to one of infinite possible stationary states. Addition of six-wave interactions term leads to appearance of collapses that eventually are regularized by the dumping terms. The energy lost during regularization of collapses in (2) is restored by the pumping term. In the latter case the system does not demonstrate relaxation-like behavior. We measure evolution of spectra Ik =< |Ψk|2 >, spatial correlation functions and the PDFs for waves amplitudes |Ψ|, concentrating special attention on formation of "fat tails" on the PDFs. For the classical integrable NLS equation (1) with condensate initial condition we observe Rayleigh tails for extremely large waves and a "breathing region" for middle waves with oscillations of the frequency of waves appearance with time, while nonintegrable NLS equation with dumping and pumping terms (2) with the absence of six-wave interactions α = 0 demonstrates perfectly Rayleigh PDFs without any oscillations with time. In case of the cnoidal wave initial condition we observe severely non-Rayleigh PDFs for the classical NLS equation (1) with the regions corresponding to 2-, 3- and so on soliton collisions clearly seen of the PDFs. Addition of six-wave interactions in Eq. (2) for condensate initial condition results in appearance of non-Rayleigh addition to the PDFs that increase with six-wave interaction constant α and disappears with the absence of six-wave interactions α = 0. References: [1] D.S. Agafontsev, V.E. Zakharov, Rogue waves statistics in the framework of one-dimensional Generalized Nonlinear Schrodinger Equation, arXiv:1202.5763v3.

Integrating a New Medicinal Chemistry and Pharmacology Course Sequence into the PharmD Curriculum

PubMed Central

Engels, Melanie; Garcia, George

2015-01-01

Objective. To evaluate the implementation of an integrated medicinal chemistry/pharmacology course sequence and its alignment with a therapeutics series. Design. Each topic was divided into modules consisting of 2-hour blocks, and the content was integrated and aligned with the therapeutics series. Recitation sessions emphasizing application skills in an interactive environment followed each of three 2-hour blocks. To ensure that students achieved competency in each unit, students failing any unit examination were encouraged to undergo remediation. Assessment. Student feedback was collected by an independent researcher through social media and focus groups and relayed anonymously to course directors for midcourse improvements. Responses from surveys, interviews, and student ratings of faculty members and of courses were used to implement changes for future editions of the courses. Conclusion. The majority of students and faculty members felt the integration and alignment processes were beneficial changes to the curriculum. Elements of the new sequence, including remediation, were viewed positively by students and faculty members as well. PMID:25741029

Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

ERIC Educational Resources Information Center

Florida, Jennifer

2012-01-01

The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

DATA COLLECTION MANAGER MODULE OF REGION III'S MULTI-CRITERIA INTEGRATED RESOURCE ASSESSMENT (MIRA) ENVIRONMENTAL DECISION MAKING APPROACH

EPA Science Inventory

This proposal pertains to the on-going development of the Data Collection Manager (DCM) module, which is one of three modules that compose MIRA, Multi-criteria Integrated Resource Assessment. MIRA is Region III's newly conceived and continually developing decision support approac...

Versatile communication strategies among tandem WW domain repeats

PubMed Central

Dodson, Emma Joy; Fishbain-Yoskovitz, Vered; Rotem-Bamberger, Shahar

2015-01-01

Interactions mediated by short linear motifs in proteins play major roles in regulation of cellular homeostasis since their transient nature allows for easy modulation. We are still far from a full understanding and appreciation of the complex regulation patterns that can be, and are, achieved by this type of interaction. The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions. This review is an attempt to overview, and classify, different ways by which two and more tandem repeats cooperate in binding to their targets, in the well-characterized family of WW domains and their corresponding polyproline ligands. PMID:25710931

Applying Economics Using Interactive Learning Modules

ERIC Educational Resources Information Center

Goma, Ophelia D.

2010-01-01

This article describes the use of web-based, interactive learning modules in the principles of economics course. The learning modules introduce students to important, historical economic events while providing real-world application of the economic theory presented in class. Each module is designed to supplement and complement the economic theory…

High extinction ratio integrated optical modulator for quantum telecommunication systems

NASA Astrophysics Data System (ADS)

Tronev, A.; Parfenov, M.; Agruzov, P.; Ilichev, I.; Shamray, A.

2018-01-01

A method for increasing the extinction ratio of integrated optical Mach-Zehnder modulators based on LiNbO3 via the photorefractive effect is proposed. The influence of the photorefractive effect on the X- and Y-splitters of intensity modulators is experimentally studied. An increase in the modulator extinction ratio by 17 dB (from 30 to 47 dB) is obtained. It is shown that fabricated modulators with a high extinction ratio are important for quantum key distribution systems.

Aerosol and monsoon climate interactions over Asia

NASA Astrophysics Data System (ADS)

Li, Zhanqing; Lau, W. K.-M.; Ramanathan, V.; Wu, G.; Ding, Y.; Manoj, M. G.; Liu, J.; Qian, Y.; Li, J.; Zhou, T.; Fan, J.; Rosenfeld, D.; Ming, Y.; Wang, Y.; Huang, J.; Wang, B.; Xu, X.; Lee, S.-S.; Cribb, M.; Zhang, F.; Yang, X.; Zhao, C.; Takemura, T.; Wang, K.; Xia, X.; Yin, Y.; Zhang, H.; Guo, J.; Zhai, P. M.; Sugimoto, N.; Babu, S. S.; Brasseur, G. P.

2016-12-01

The increasing severity of droughts/floods and worsening air quality from increasing aerosols in Asia monsoon regions are the two gravest threats facing over 60% of the world population living in Asian monsoon regions. These dual threats have fueled a large body of research in the last decade on the roles of aerosols in impacting Asian monsoon weather and climate. This paper provides a comprehensive review of studies on Asian aerosols, monsoons, and their interactions. The Asian monsoon region is a primary source of emissions of diverse species of aerosols from both anthropogenic and natural origins. The distributions of aerosol loading are strongly influenced by distinct weather and climatic regimes, which are, in turn, modulated by aerosol effects. On a continental scale, aerosols reduce surface insolation and weaken the land-ocean thermal contrast, thus inhibiting the development of monsoons. Locally, aerosol radiative effects alter the thermodynamic stability and convective potential of the lower atmosphere leading to reduced temperatures, increased atmospheric stability, and weakened wind and atmospheric circulations. The atmospheric thermodynamic state, which determines the formation of clouds, convection, and precipitation, may also be altered by aerosols serving as cloud condensation nuclei or ice nuclei. Absorbing aerosols such as black carbon and desert dust in Asian monsoon regions may also induce dynamical feedback processes, leading to a strengthening of the early monsoon and affecting the subsequent evolution of the monsoon. Many mechanisms have been put forth regarding how aerosols modulate the amplitude, frequency, intensity, and phase of different monsoon climate variables. A wide range of theoretical, observational, and modeling findings on the Asian monsoon, aerosols, and their interactions are synthesized. A new paradigm is proposed on investigating aerosol-monsoon interactions, in which natural aerosols such as desert dust, black carbon from biomass burning, and biogenic aerosols from vegetation are considered integral components of an intrinsic aerosol-monsoon climate system, subject to external forcing of global warming, anthropogenic aerosols, and land use and change. Future research on aerosol-monsoon interactions calls for an integrated approach and international collaborations based on long-term sustained observations, process measurements, and improved models, as well as using observations to constrain model simulations and projections.

Fermi-Pasta-Ulam recurrence and modulation instability

NASA Astrophysics Data System (ADS)

Kuznetsov, E. A.

2017-01-01

We give a qualitative conceptual explanation of the Fermi-Pasta-Ulam (FPU) like recurrence in the onedimensional focusing nonlinear Schrodinger equation (NLSE). The recurrence can be considered as a result of the nonlinear development of the modulation instability. All known exact localized solitary wave solutions describing propagation on the background of the modulationally unstable condensate show the recurrence to the condensate state after its interaction with solitons. The condensate state locally recovers its original form with the same amplitude but a different phase after soliton leave its initial region. Based on the integrability of the NLSE, we demonstrate that the FPU recurrence takes place not only for condensate, but also for a more general solution in the form of the cnoidal wave. This solution is periodic in space and can be represented as a solitonic lattice. That lattice reduces to isolated soliton solution in the limit of large distance between solitons. The lattice transforms into the condensate in the opposite limit of dense soliton packing. The cnoidal wave is also modulationally unstable due to soliton overlapping. The recurrence happens at the nonlinear stage of the modulation instability. Due to generic nature of the underlying mathematical model, the proposed concept can be applied across disciplines and nonlinear systems, ranging from optical communications to hydrodynamics.

Attention to Multiple Objects Facilitates Their Integration in Prefrontal and Parietal Cortex.

PubMed

Kim, Yee-Joon; Tsai, Jeffrey J; Ojemann, Jeffrey; Verghese, Preeti

2017-05-10

Selective attention is known to interact with perceptual organization. In visual scenes, individual objects that are distinct and discriminable may occur on their own, or in groups such as a stack of books. The main objective of this study is to probe the neural interaction that occurs between individual objects when attention is directed toward one or more objects. Here we record steady-state visual evoked potentials via electrocorticography to directly assess the responses to individual stimuli and to their interaction. When human participants attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective enhancement of only the neural interaction between stimuli, but not the responses to individual stimuli. When only one stimulus is attended, the neural response to that stimulus is selectively enhanced in prefrontal and parietal cortex. In contrast, early visual areas generally manifest responses to individual stimuli and to their interaction regardless of attentional task, although a subset of the responses is modulated similarly to prefrontal and parietal cortex. Thus, the neural representation of the visual scene as one progresses up the cortical hierarchy becomes more highly task-specific and represents either individual stimuli or their interaction, depending on the behavioral goal. Attention to multiple objects facilitates an integration of objects akin to perceptual grouping. SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as distinct entities or as parts of a whole. Here we examine how attention to multiple objects affects their neural representation. Previous studies measured single-cell or fMRI responses and obtained only aggregate measures that combined the activity to individual stimuli as well as their potential interaction. Here, we directly measure electrocorticographic steady-state responses corresponding to individual objects and to their interaction using a frequency-tagging technique. Attention to two stimuli increases the interaction component that is a hallmark for perceptual integration of stimuli. Furthermore, this stimulus-specific interaction is represented in prefrontal and parietal cortex in a task-dependent manner. Copyright © 2017 the authors 0270-6474/17/374942-12$15.00/0.

"Flipping" the introductory clerkship in radiology: impact on medical student performance and perceptions.

PubMed

Belfi, Lily M; Bartolotta, Roger J; Giambrone, Ashley E; Davi, Caryn; Min, Robert J

2015-06-01

Among methods of "blended learning" (ie, combining online modules with in-class instruction), the "flipped classroom" involves student preclass review of material while reserving class time for interactive knowledge application. We integrated blended learning methodology in a "flipped" introductory clerkship in radiology, and assessed the impact of this approach on the student educational experience (performance and perception). In preparation for the "flipped clerkship," radiology faculty and residents created e-learning modules that were uploaded to an open-source website. The clerkship's 101 rising third-year medical students were exposed to different teaching methods during the course, such as blended learning, traditional lecture learning, and independent learning. Students completed precourse and postcourse knowledge assessments and surveys. Student knowledge improved overall as a result of taking the course. Blended learning achieved greater pretest to post-test improvement of high statistical significance (P value, .0060) compared to lecture learning alone. Blended learning also achieved greater pretest to post-test improvement of borderline statistical significance (P value, .0855) in comparison to independent learning alone. The difference in effectiveness of independent learning versus lecture learning was not statistically significant (P value, .2730). Student perceptions of the online modules used in blended learning portions of the course were very positive. They specifically enjoyed the self-paced interactivity and the ability to return to the modules in the future. Blended learning can be successfully applied to the introductory clerkship in radiology. This teaching method offers educators an innovative and efficient approach to medical student education in radiology. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment.

PubMed

Versari, Silvia; Longinotti, Giulia; Barenghi, Livia; Maier, Jeanette Anne Marie; Bradamante, Silvia

2013-11-01

Exposure to microgravity generates alterations that are similar to those involved in age-related diseases, such as cardiovascular deconditioning, bone loss, muscle atrophy, and immune response impairment. Endothelial dysfunction is the common denominator. To shed light on the underlying mechanism, we participated in the Progress 40P mission with Spaceflight of Human Umbilical Vein Endothelial Cells (HUVECs): an Integrated Experiment (SPHINX), which consisted of 12 in-flight and 12 ground-based control modules and lasted 10 d. Postflight microarray analysis revealed 1023 significantly modulated genes, the majority of which are involved in cell adhesion, oxidative phosphorylation, stress responses, cell cycle, and apoptosis. Thioredoxin-interacting protein was the most up-regulated (33-fold), heat-shock proteins 70 and 90 the most down-regulated (5.6-fold). Ion channels (TPCN1, KCNG2, KCNJ14, KCNG1, KCNT1, TRPM1, CLCN4, CLCA2), mitochondrial oxidative phosphorylation, and focal adhesion were widely affected. Cytokine detection in the culture media indicated significant increased secretion of interleukin-1α and interleukin-1β. Nitric oxide was found not modulated. Our data suggest that in cultured HUVECs, microgravity affects the same molecular machinery responsible for sensing alterations of flow and generates a prooxidative environment that activates inflammatory responses, alters endothelial behavior, and promotes senescence.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

PubMed

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks

PubMed Central

Li, Min; Li, Dongyan; Tang, Yu; Wang, Jianxin

2017-01-01

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster. PMID:28858211

Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.

PubMed

Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

2016-06-15

Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

Inborn errors of metabolism and the human interactome: a systems medicine approach.

PubMed

Woidy, Mathias; Muntau, Ania C; Gersting, Søren W

2018-02-05

The group of inborn errors of metabolism (IEM) displays a marked heterogeneity and IEM can affect virtually all functions and organs of the human organism; however, IEM share that their associated proteins function in metabolism. Most proteins carry out cellular functions by interacting with other proteins, and thus are organized in biological networks. Therefore, diseases are rarely the consequence of single gene mutations but of the perturbations caused in the related cellular network. Systematic approaches that integrate multi-omics and database information into biological networks have successfully expanded our knowledge of complex disorders but network-based strategies have been rarely applied to study IEM. We analyzed IEM on a proteome scale and found that IEM-associated proteins are organized as a network of linked modules within the human interactome of protein interactions, the IEM interactome. Certain IEM disease groups formed self-contained disease modules, which were highly interlinked. On the other hand, we observed disease modules consisting of proteins from many different disease groups in the IEM interactome. Moreover, we explored the overlap between IEM and non-IEM disease genes and applied network medicine approaches to investigate shared biological pathways, clinical signs and symptoms, and links to drug targets. The provided resources may help to elucidate the molecular mechanisms underlying new IEM, to uncover the significance of disease-associated mutations, to identify new biomarkers, and to develop novel therapeutic strategies.

HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology

PubMed Central

Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C.; Sahinalp, S. Cenk

2017-01-01

Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the “random walk facility location” (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: “multihitting time,” the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. PMID:28768687

User-centered design and usability testing of an innovative health-related quality of life module.

PubMed

Nagykaldi, Z J; Jordan, M; Quitoriano, J; Ciro, C A; Mold, J W

2014-01-01

Various computerized health risk appraisals (HRAs) are available, but few of them assess health-related quality of life (HRQoL) in a goal-directed framework. This study describes the user-centered development and usability testing of an innovative HRQoL module that extends a validated HRA tool in primary care settings. Systematic user-centered design, usability testing, and qualitative methods were used to develop the HRQoL module in primary care practices. Twenty two patients and 5 clinicians participated in two rounds of interactive technology think-out-loud sessions (TOLs) and semi-structured interviews (SSIs) to iteratively develop a four-step, computerized process that collects information on patient goals for meaningful life activities and current level of disability and presents a personalized and prioritized list of preventive recommendations linked to online resources. Analysis of TOLs and SSIs generated 5 categories and 11 sub-categories related to facilitators and barriers to usability and human-technology interaction. The categories included: Understanding the Purpose, Usability, Perceived Value, Literacy, and Participant Motivation. Some categories were inter-connected. The technology was continually and iteratively improved between sessions until saturation of positive feedback was achieved in 4 categories (addressing motivation will require more research). Usability of all screen units of the module was improved substantially. Clinician feedback emphasized the importance of the module's ability to translate the patient-centered HRQoL Report into actionable items for clinicians to facilitate shared decision-making. Complete integration of the HRQoL module into the existing HRA will require further development and testing. Systematic application of user-centered design and human factors principles in technology development and testing may significantly improve the usability and clinical value of health information systems. This more sophisticated approach helped us translate complex clinical concepts, goal-setting steps, and decision-support processes into an accepted and value-added technology.

Cosmic ray modulation and turbulent interaction regions near 11 AU

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Mcdonald, F. B.; Goldstein, M. L.; Lazarus, A. J.

1985-01-01

When Voyager 2 was near 11 AU, the counting rate of nuclei approx 75 MeV/nucleon decreased during the interval from July, 1982 to November, 1982, and it increased thereafter until August, 1983. A decrease in cosmic ray flux was generally associated with the passage of an interaction region in which the magnetic field strength B was higher than that predicted by the spiral field model, B sub p. Several large enhancements in B/B sup p were associated with merged interaction regions which probably resulted from the interaction of two or more distinct flows. During the passage of interaction regions the cosmic ray intensity decreased at a rate proportional to (B/B sup p -1), and during the passage of rarefaction regions (where B/B sup p 1) the cosmic ray intensity increased at a constant rate. The general form of the cosmic ray intensity profile during this approx 13 month minicycle can be described by integrating these relations using the observed B(t). Latitudinal variations of the interaction regions and of the short-term cosmic ray variations were identified.

Functional Interaction Network Construction and Analysis for Disease Discovery.

PubMed

Wu, Guanming; Haw, Robin

2017-01-01

Network-based approaches project seemingly unrelated genes or proteins onto a large-scale network context, therefore providing a holistic visualization and analysis platform for genomic data generated from high-throughput experiments, reducing the dimensionality of data via using network modules and increasing the statistic analysis power. Based on the Reactome database, the most popular and comprehensive open-source biological pathway knowledgebase, we have developed a highly reliable protein functional interaction network covering around 60 % of total human genes and an app called ReactomeFIViz for Cytoscape, the most popular biological network visualization and analysis platform. In this chapter, we describe the detailed procedures on how this functional interaction network is constructed by integrating multiple external data sources, extracting functional interactions from human curated pathway databases, building a machine learning classifier called a Naïve Bayesian Classifier, predicting interactions based on the trained Naïve Bayesian Classifier, and finally constructing the functional interaction database. We also provide an example on how to use ReactomeFIViz for performing network-based data analysis for a list of genes.

Vocal and visual stimulation, congruence and lateralization affect brain oscillations in interspecies emotional positive and negative interactions.

PubMed

Balconi, Michela; Vanutelli, Maria Elide

2016-01-01

The present research explored the effect of cross-modal integration of emotional cues (auditory and visual (AV)) compared with only visual (V) emotional cues in observing interspecies interactions. The brain activity was monitored when subjects processed AV and V situations, which represented an emotional (positive or negative), interspecies (human-animal) interaction. Congruence (emotionally congruous or incongruous visual and auditory patterns) was also modulated. electroencephalography brain oscillations (from delta to beta) were analyzed and the cortical source localization (by standardized Low Resolution Brain Electromagnetic Tomography) was applied to the data. Frequency band (mainly low-frequency delta and theta) showed a significant brain activity increasing in response to negative compared to positive interactions within the right hemisphere. Moreover, differences were found based on stimulation type, with an increased effect for AV compared with V. Finally, delta band supported a lateralized right dorsolateral prefrontal cortex (DLPFC) activity in response to negative and incongruous interspecies interactions, mainly for AV. The contribution of cross-modality, congruence (incongruous patterns), and lateralization (right DLPFC) in response to interspecies emotional interactions was discussed at light of a "negative lateralized effect."

Testing the interaction between analytical modules: an example with Roundup Ready® soybean line GTS 40-3-2

PubMed Central

2010-01-01

Background The modular approach to analysis of genetically modified organisms (GMOs) relies on the independence of the modules combined (i.e. DNA extraction and GM quantification). The validity of this assumption has to be proved on the basis of specific performance criteria. Results An experiment was conducted using, as a reference, the validated quantitative real-time polymerase chain reaction (PCR) module for detection of glyphosate-tolerant Roundup Ready® GM soybean (RRS). Different DNA extraction modules (CTAB, Wizard and Dellaporta), were used to extract DNA from different food/feed matrices (feed, biscuit and certified reference material [CRM 1%]) containing the target of the real-time PCR module used for validation. Purity and structural integrity (absence of inhibition) were used as basic criteria that a DNA extraction module must satisfy in order to provide suitable template DNA for quantitative real-time (RT) PCR-based GMO analysis. When performance criteria were applied (removal of non-compliant DNA extracts), the independence of GMO quantification from the extraction method and matrix was statistically proved, except in the case of Wizard applied to biscuit. A fuzzy logic-based procedure also confirmed the relatively poor performance of the Wizard/biscuit combination. Conclusions For RRS, this study recognises that modularity can be generally accepted, with the limitation of avoiding combining highly processed material (i.e. biscuit) with a magnetic-beads system (i.e. Wizard). PMID:20687918

Features and functions of nonlinear spatial integration by retinal ganglion cells.

PubMed

Gollisch, Tim

2013-11-01

Ganglion cells in the vertebrate retina integrate visual information over their receptive fields. They do so by pooling presynaptic excitatory inputs from typically many bipolar cells, which themselves collect inputs from several photoreceptors. In addition, inhibitory interactions mediated by horizontal cells and amacrine cells modulate the structure of the receptive field. In many models, this spatial integration is assumed to occur in a linear fashion. Yet, it has long been known that spatial integration by retinal ganglion cells also incurs nonlinear phenomena. Moreover, several recent examples have shown that nonlinear spatial integration is tightly connected to specific visual functions performed by different types of retinal ganglion cells. This work discusses these advances in understanding the role of nonlinear spatial integration and reviews recent efforts to quantitatively study the nature and mechanisms underlying spatial nonlinearities. These new insights point towards a critical role of nonlinearities within ganglion cell receptive fields for capturing responses of the cells to natural and behaviorally relevant visual stimuli. In the long run, nonlinear phenomena of spatial integration may also prove important for implementing the actual neural code of retinal neurons when designing visual prostheses for the eye. Copyright © 2012 Elsevier Ltd. All rights reserved.

Integrable high order UWB pulse photonic generator based on cross phase modulation in a SOA-MZI.

PubMed

Moreno, Vanessa; Rius, Manuel; Mora, José; Muriel, Miguel A; Capmany, José

2013-09-23

We propose and experimentally demonstrate a potentially integrable optical scheme to generate high order UWB pulses. The technique is based on exploiting the cross phase modulation generated in an InGaAsP Mach-Zehnder interferometer containing integrated semiconductor optical amplifiers, and is also adaptable to different pulse modulation formats through an optical processing unit which allows to control of the amplitude, polarity and time delay of the generated taps.

The cognitive impact of interactive design features for learning complex materials in medical education.

PubMed

Song, Hyuksoon S; Pusic, Martin; Nick, Michael W; Sarpel, Umut; Plass, Jan L; Kalet, Adina L

2014-02-01

To identify the most effective way for medical students to interact with a browser-based learning module on the symptoms and neurological underpinnings of stroke syndromes, this study manipulated the way in which subjects interacted with a graphical model of the brain and examined the impact of functional changes on learning outcomes. It was hypothesized that behavioral interactions that were behaviorally more engaging and which required deeper consideration of the model would result in heightened cognitive interaction and better learning than those whose manipulation required less deliberate behavioral and cognitive processing. One hundred forty four students were randomly assigned to four conditions whose model controls incorporated features that required different levels of behavioral and cognitive interaction: Movie (low behavioral/low cognitive, n = 40), Slider (high behavioral/low cognitive, n = 36), Click (low behavioral/high cognitive, n = 30), and Drag (high behavioral/high cognitive, n = 38). Analysis of Covariates (ANCOVA) showed that students who received the treatments associated with lower cognitive interactivity (Movie and Slider) performed better on a transfer task than those receiving the module associated with high cognitive interactivity (Click and Drag, partial eta squared = .03). In addition, the students in the high cognitive interactivity conditions spent significantly more time on the stroke locator activity than other conditions (partial eta squared = .36). The results suggest that interaction with controls that were tightly coupled with the model and whose manipulation required deliberate consideration of the model's features may have overtaxed subjects' cognitive resources. Cognitive effort that facilitated manipulation of content, though directed at the model, may have resulted in extraneous cognitive load, impeding subjects in recognizing the deeper, global relationships in the materials. Instructional designers must, therefore, keep in mind that the way in which functional affordances are integrated with the content can shape both behavioral and cognitive processing, and has significant cognitive load implications.

Design and Analysis of Enhanced Modulation Response in Integrated Coupled Cavities DBR Lasers Using Photon-Photon Resonance

DOE PAGES

Bardella, Paolo; Chow, Weng; Montrosset, Ivo

2016-01-08

In the last decades, various solutions have been proposed to increase the modulation bandwidth and consequently the transmission bit rate of integrated semiconductor lasers. In this manuscript we discuss a design procedure for a recently proposed laser structure realized with the integration of two DBR lasers. Design guidelines will be proposed and dynamic small and large signal simulations, calculated using a Finite Difference Traveling Wave numerical simulator, will be performed to confirm the design results and the effectiveness of the analyzed integrated configuration to achieve a direct modulation bandwidth up to 80 GHz

Ground Operations Autonomous Control and Integrated Health Management

NASA Technical Reports Server (NTRS)

Daniels, James

2014-01-01

The Ground Operations Autonomous Control and Integrated Health Management plays a key role for future ground operations at NASA. The software that is integrated into this system is called G2 2011 Gensym. The purpose of this report is to describe the Ground Operations Autonomous Control and Integrated Health Management with the use of the G2 Gensym software and the G2 NASA toolkit for Integrated System Health Management (ISHM) which is a Computer Software Configuration Item (CSCI). The decision rationale for the use of the G2 platform is to develop a modular capability for ISHM and AC. Toolkit modules include knowledge bases that are generic and can be applied in any application domain module. That way, there's a maximization of reusability, maintainability, and systematic evolution, portability, and scalability. Engine modules are generic, while application modules represent the domain model of a specific application. Furthermore, the NASA toolkit, developed since 2006 (a set of modules), makes it possible to create application domain models quickly, using pre-defined objects that include sensors and components libraries for typical fluid, electrical, and mechanical systems.

Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe.

PubMed

Liu, C C; Crone, N E; Franaszczuk, P J; Cheng, D T; Schretlen, D S; Lenz, F A

2011-08-25

The current model of fear conditioning suggests that it is mediated through modules involving the amygdala (AMY), hippocampus (HIP), and frontal lobe (FL). We now test the hypothesis that habituation and acquisition stages of a fear conditioning protocol are characterized by different event-related causal interactions (ERCs) within and between these modules. The protocol used the painful cutaneous laser as the unconditioned stimulus and ERC was estimated by analysis of local field potentials recorded through electrodes implanted for investigation of epilepsy. During the prestimulus interval of the habituation stage FL>AMY ERC interactions were common. For comparison, in the poststimulus interval of the habituation stage, only a subdivision of the FL (dorsolateral prefrontal cortex, dlPFC) still exerted the FL>AMY ERC interaction (dlFC>AMY). For a further comparison, during the poststimulus interval of the acquisition stage, the dlPFC>AMY interaction persisted and an AMY>FL interaction appeared. In addition to these ERC interactions between modules, the results also show ERC interactions within modules. During the poststimulus interval, HIP>HIP ERC interactions were more common during acquisition, and deep hippocampal contacts exerted causal interactions on superficial contacts, possibly explained by connectivity between the perihippocampal gyrus and the HIP. During the prestimulus interval of the habituation stage, AMY>AMY ERC interactions were commonly found, while interactions between the deep and superficial AMY (indirect pathway) were independent of intervals and stages. These results suggest that the network subserving fear includes distributed or widespread modules, some of which are themselves "local networks." ERC interactions between and within modules can be either static or change dynamically across intervals or stages of fear conditioning. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Apparatus and methods for packaging integrated circuit chips with antenna modules providing closed electromagnetic environment for integrated antennas

NASA Technical Reports Server (NTRS)

Gaucher, Brian P. (Inventor); Grzyb, Janusz (Inventor); Liu, Duixian (Inventor); Pfeiffer, Ullrich R. (Inventor)

2008-01-01

Apparatus and methods are provided for packaging IC chips together with integrated antenna modules designed to provide a closed EM (electromagnetic) environment for antenna radiators, thereby allowing antennas to be designed independent from the packaging technology.

Developing a blended course on dying, loss, and grief.

PubMed

Kavanaugh, Karen; Andreoni, V Ann; Wilkie, Diana J; Burgener, Sandra; Buschmann, Mary Beth Tank; Henderson, Gloria; Hsiung, Yi-Fang Yvonne; Zhao, Zhongsheng

2009-01-01

An important component of end-of-life education is to provide health professionals with content related to dying, loss, and grief. The authors describe the strategies used to develop and offer a blended course (integration of classroom face-to-face learning with online learning) that addressed the sensitive and often emotional content associated with grieving and bereavement. Using Kolb's Experiential Learning Theory, a set of 4 online learning modules, with engaging, interactive elements, was created. Course evaluations demonstrated the success of the blended course in comparison to the traditional, exclusive face-to-face approach.

EWB: The Environment WorkBench Version 4.0

NASA Technical Reports Server (NTRS)

1995-01-01

The Environment WorkBench EWB is a desktop integrated analysis tool for studying a spacecraft's interactions with its environment. Over 100 environment and analysis models are integrated into the menu-based tool. EWB, which was developed for and under the guidance of the NASA Lewis Research Center, is built atop the Module Integrator and Rule-based Intelligent Analytic Database (MIRIAD) architecture. This allows every module in EWB to communicate information to other modules in a transparent manner from the user's point of view. It removes the tedious and error-prone steps of entering data by hand from one model to another. EWB runs under UNIX operating systems (SGI and SUN workstations) and under MS Windows (3.x, 95, and NT) operating systems. MIRIAD, the unique software that makes up the core of EWB, provides the flexibility to easily modify old models and incorporate new ones as user needs change. The MIRIAD approach separates the computer assisted engineering (CAE) tool into three distinct units: 1) A modern graphical user interface to present information; 2) A data dictionary interpreter to coordinate analysis; and 3) A database for storing system designs and analysis results. The user interface is externally programmable through ASCII data files, which contain the location and type of information to be displayed on the screen. This approach provides great flexibility in tailoring the look and feel of the code to individual user needs. MIRIADbased applications, such as EWB, have utilities for viewing tabulated parametric study data, XY line plots, contour plots, and three-dimensional plots of contour data and system geometries. In addition, a Monte Carlo facility is provided to allow statistical assessments (including uncertainties) in models or data.

a Webgis to Support Gpr 3d Data Acquisition: a First Step for the Integration of Underground Utility Networks in 3d City Models

NASA Astrophysics Data System (ADS)

Tabarro, P. G.; Pouliot, J.; Fortier, R.; Losier, L.-M.

2017-10-01

For the planning and sustainable development of large cities, it is critical to accurately locate and map, in 3D, existing underground utility networks (UUN) such as pipelines, cables, ducts, and channels. An emerging non-invasive instrument for collecting underground data such as UUN is the ground-penetrating radar (GPR). Although its capabilities, handling GPR and extracting relevant information from its data are not trivial tasks. For instance, both GPR and its complimentary software stack provide very few capabilities to co-visualize GPR collected data and other sources of spatial data such as orthophotography, DEM or road maps. Furthermore, the GPR interface lacks functionalities for adding annotation, editing geometric objects or querying attributes. A new approach to support GPR survey is proposed in this paper. This approach is based on the integration of multiple sources of geospatial datasets and the use of a Web-GIS system and relevant functionalities adapted to interoperable GPR data acquisition. The Web-GIS is developed as an improved module in an existing platform called GVX. The GVX-GPR module provides an interactive visualization of multiple layers of structured spatial data, including GPR profiles. This module offers new features when compared to traditional GPR surveys such as geo-annotated points of interest for identifying spatial clues in the GPR profiles, integration of city contextual data, high definition drone and satellite pictures, as-built, and more. The paper explains the engineering approach used to design and develop the Web GIS and tests for this survey approach, mapping and recording UUN as part of 3D city model.

Learning other agents` preferences in multiagent negotiation

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

Bui, H.H.; Kieronska, D.; Venkatesh, S.

In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complementmore » knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).« less

Electro-optical co-simulation for integrated CMOS photonic circuits with VerilogA.

PubMed

Sorace-Agaskar, Cheryl; Leu, Jonathan; Watts, Michael R; Stojanovic, Vladimir

2015-10-19

We present a Cadence toolkit library written in VerilogA for simulation of electro-optical systems. We have identified and described a set of fundamental photonic components at the physical level such that characteristics of composite devices (e.g. ring modulators) are created organically - by simple instantiation of fundamental primitives. Both the amplitude and phase of optical signals as well as optical-electrical interactions are simulated. We show that the results match other simulations and analytic solutions that have previously been compared to theory for both simple devices, such as ring resonators, and more complicated devices and systems such as single-sideband modulators, WDM links and Pound Drever Hall Locking loops. We also illustrate the capability of such toolkit for co-simulation with electronic circuits, which is a key enabler of the electro-optic system development and verification.

Enhancement of the static extinction ratio by using a dual-section distributed feedback laser integrated with an electro-absorption modulator

NASA Astrophysics Data System (ADS)

Cho, Chun-Hyung; Kim, Jongseong; Sung, Hyuk-Kee

2016-09-01

We report on the enhancement of the static extinction ratio by using a dual-section distributed feedback laser diode integrated with an electro-absorption modulator. A directly- modulated dual-section laser can provide improved modulation performance under a low bias level ( i.e., below the threshold level) compared with a standard directly-modulated laser. By combining the extinction ratio from a dual-section laser with that from an electro-absorption modulator section, a total extinction ratio of 49.6. dB are successfully achieved.

Demonstration of a simplified optical mouse lighting module by integrating the non-Lambertian LED chip and the free-form surface.

PubMed

Pan, Jui-Wen; Tu, Sheng-Han

2012-05-20

A cost-effective, high-throughput, and high-yield method for the efficiency enhancement of an optical mouse lighting module is proposed. We integrated imprinting technology and free-form surface design to obtain a lighting module with high illumination efficiency and uniform intensity distribution. The imprinting technique can increase the light extraction efficiency and modulate the intensity distribution of light-emitting diodes. A modulated light source was utilized to add a compact free-form surface element to create a lighting module with 95% uniformity and 80% optical efficiency.

Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia.

PubMed

Milstein, Michelle L; Musa, Hassan; Balbuena, Daniela Ponce; Anumonwo, Justus M B; Auerbach, David S; Furspan, Philip B; Hou, Luqia; Hu, Bin; Schumacher, Sarah M; Vaidyanathan, Ravi; Martens, Jeffrey R; Jalife, José

2012-07-31

The cardiac electrical impulse depends on an orchestrated interplay of transmembrane ionic currents in myocardial cells. Two critical ionic current mechanisms are the inwardly rectifying potassium current (I(K1)), which is important for maintenance of the cell resting membrane potential, and the sodium current (I(Na)), which provides a rapid depolarizing current during the upstroke of the action potential. By controlling the resting membrane potential, I(K1) modifies sodium channel availability and therefore, cell excitability, action potential duration, and velocity of impulse propagation. Additionally, I(K1)-I(Na) interactions are key determinants of electrical rotor frequency responsible for abnormal, often lethal, cardiac reentrant activity. Here, we have used a multidisciplinary approach based on molecular and biochemical techniques, acute gene transfer or silencing, and electrophysiology to show that I(K1)-I(Na) interactions involve a reciprocal modulation of expression of their respective channel proteins (Kir2.1 and Na(V)1.5) within a macromolecular complex. Thus, an increase in functional expression of one channel reciprocally modulates the other to enhance cardiac excitability. The modulation is model-independent; it is demonstrable in myocytes isolated from mouse and rat hearts and with transgenic and adenoviral-mediated overexpression/silencing. We also show that the post synaptic density, discs large, and zonula occludens-1 (PDZ) domain protein SAP97 is a component of this macromolecular complex. We show that the interplay between Na(v)1.5 and Kir2.1 has electrophysiological consequences on the myocardium and that SAP97 may affect the integrity of this complex or the nature of Na(v)1.5-Kir2.1 interactions. The reciprocal modulation between Na(v)1.5 and Kir2.1 and the respective ionic currents should be important in the ability of the heart to undergo self-sustaining cardiac rhythm disturbances.

Integral bypass diodes in an amorphous silicon alloy photovoltaic module

NASA Technical Reports Server (NTRS)

Hanak, J. J.; Flaisher, H.

1991-01-01

Thin-film, tandem-junction, amorphous silicon (a-Si) photovoltaic modules were constructed in which a part of the a-Si alloy cell material is used to form bypass protection diodes. This integral design circumvents the need for incorporating external, conventional diodes, thus simplifying the manufacturing process and reducing module weight.

Integrating Oracle Human Resources with Other Modules

NASA Technical Reports Server (NTRS)

Sparks, Karl; Shope, Shawn

1998-01-01

One of the most challenging aspects of implementing an enterprise-wide business system is achieving integration of the different modules to the satisfaction of diverse customers. The Jet Propulsion Laboratory's (JPL) implementation of the Oracle application suite demonstrates the need to coordinate Oracle Human Resources Management System (HRMS) decision across the Oracle modules.

Drosophila genetics in the classroom.

PubMed

Sofer, W; Tompkins, L

1994-01-01

Drosophila has long been useful for demonstrating the principles of classical Mendelian genetics in the classroom. In recent years, the organism has also helped students understand biochemical and behavioral genetics. In this connection, this article describes the development of a set of integrated laboratory exercises and descriptive materials--a laboratory module--in biochemical genetics for use by high-school students. The module focuses on the Adh gene and its product, the alcohol dehydrogenase enzyme. Among other activities, students using the module get to measure alcohol tolerance and to assay alcohol dehydrogenase activity in Adh-negative and -positive flies. To effectively present the module in the classroom, teachers attend a month-long Dissemination Institute in the summer. During this period, they learn about other research activities that can be adapted for classroom use. One such activity that has proved popular with teachers and students utilizes Drosophila to introduce some of the concepts of behavioral genetics to the high-school student. By establishing closer interactions between high-school educators and research scientists, the gulf between the two communities can begin to be bridged. It is anticipated that the result of a closer relationship will be that the excitement and creativity of science will be more effectively conveyed to students.

Cryptochrome 1 interacts with PIF4 to regulate high temperature-mediated hypocotyl elongation in response to blue light.

PubMed

Ma, Dingbang; Li, Xu; Guo, Yongxia; Chu, Jingfang; Fang, Shuang; Yan, Cunyu; Noel, Joseph P; Liu, Hongtao

2016-01-05

Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors [CRY1 and PHYTOCHROME B (PHYB)] and ambient temperature can mediate morphological responses through the same signaling component-PIF4.

Interactions between facial emotion and identity in face processing: evidence based on redundancy gains.

PubMed

Yankouskaya, Alla; Booth, David A; Humphreys, Glyn

2012-11-01

Interactions between the processing of emotion expression and form-based information from faces (facial identity) were investigated using the redundant-target paradigm, in which we specifically tested whether identity and emotional expression are integrated in a superadditive manner (Miller, Cognitive Psychology 14:247-279, 1982). In Experiments 1 and 2, participants performed emotion and face identity judgments on faces with sad or angry emotional expressions. Responses to redundant targets were faster than responses to either single target when a universal emotion was conveyed, and performance violated the predictions from a model assuming independent processing of emotion and face identity. Experiment 4 showed that these effects were not modulated by varying interstimulus and nontarget contingencies, and Experiment 5 demonstrated that the redundancy gains were eliminated when faces were inverted. Taken together, these results suggest that the identification of emotion and facial identity interact in face processing.

Coupling of a distributed stakeholder-built system dynamics socio-economic model with SAHYSMOD for sustainable soil salinity management - Part 1: Model development

NASA Astrophysics Data System (ADS)

Inam, Azhar; Adamowski, Jan; Prasher, Shiv; Halbe, Johannes; Malard, Julien; Albano, Raffaele

2017-08-01

Effective policies, leading to sustainable management solutions for land and water resources, require a full understanding of interactions between socio-economic and physical processes. However, the complex nature of these interactions, combined with limited stakeholder engagement, hinders the incorporation of socio-economic components into physical models. The present study addresses this challenge by integrating the physical Spatial Agro Hydro Salinity Model (SAHYSMOD) with a participatory group-built system dynamics model (GBSDM) that includes socio-economic factors. A stepwise process to quantify the GBSDM is presented, along with governing equations and model assumptions. Sub-modules of the GBSDM, describing agricultural, economic, water and farm management factors, are linked together with feedbacks and finally coupled with the physically based SAHYSMOD model through commonly used tools (i.e., MS Excel and a Python script). The overall integrated model (GBSDM-SAHYSMOD) can be used to help facilitate the role of stakeholders with limited expertise and resources in model and policy development and implementation. Following the development of the integrated model, a testing methodology was used to validate the structure and behavior of the integrated model. Model robustness under different operating conditions was also assessed. The model structure was able to produce anticipated real behaviours under the tested scenarios, from which it can be concluded that the formulated structures generate the right behaviour for the right reasons.

Electronic Module Design with Scientifically Character-Charged Approach on Kinematics Material Learning to Improve Holistic Competence of High School Students in 10th Grade

NASA Astrophysics Data System (ADS)

Anggraini, R.; Darvina, Y.; Amir, H.; Murtiani, M.; Yulkifli, Y.

2018-04-01

The availability of modules in schools is currently lacking. Learners have not used the module as a source in the learning process. In accordance with the demands of the 2013 curriculum, that learning should be conducted using a scientific approach and loaded with character values as well as learning using interactive learning resources. The solution of this problem is to create an interactive module with a scientifically charged character approach. This interactive module can be used by learners outside the classroom or in the classroom. This interactive module contains straight motion material, parabolic motion and circular motion of high school physics class X semester 1. The purpose of this research is to produce an interactive module with a scientific approach charged with character and determine the validity and practicality. The research is Research and Development. This study was conducted only until the validity test and practice test. The validity test was conducted by three lecturers of Physics of FMIPA UNP as experts. The instruments used in this research are validation sheet and worksheet sheet. Data analysis technique used is product validity analysis. The object of this research is electronic module, while the subject of this research is three validator.

The search for Pleiades in trait constellations: functional integration and phenotypic selection in the complex flowers of Morrenia brachystephana (Apocynaceae).

PubMed

Baranzelli, M C; Sérsic, A N; Cocucci, A A

2014-04-01

Pollinator-mediated natural selection on single traits, such as corolla tube or spur length, has been well documented. However, flower phenotypes are usually complex, and selection is expected to act on several traits that functionally interact rather than on a single isolated trait. Despite the fact that selection on complex phenotypes is expectedly widespread, multivariate selection modelling on such phenotypes still remains under-explored in plants. Species of the subfamily Asclepiadoideae (Apocynaceae) provide an opportunity to study such complex flower contrivances integrated by fine-scaled organs from disparate developmental origin. We studied the correlation structure among linear floral traits (i) by testing a priori morphological, functional or developmental hypotheses among traits and (ii) by exploring the organization of flower covariation, considering alternative expectations of modular organization or whole flower integration through conditional dependence analysis (CDA) and integration matrices. The phenotypic selection approach was applied to determine whether floral traits involved in the functioning of the pollination mechanism were affected by natural selection. Floral integration was low, suggesting that flowers are organized in more than just one correlation pleiad; our hypothetical functional correlation matrix was significantly correlated with the empirical matrix, and the CDA revealed three putative modules. Analyses of phenotypic selection showed significant linear and correlational gradients, lending support to expectations of functional interactions between floral traits. Significant correlational selection gradients found involved traits of different floral whorls, providing evidence for the existence of functional integration across developmental domains. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Recursive expectation-maximization clustering: A method for identifying buffering mechanisms composed of phenomic modules

NASA Astrophysics Data System (ADS)

Guo, Jingyu; Tian, Dehua; McKinney, Brett A.; Hartman, John L.

2010-06-01

Interactions between genetic and/or environmental factors are ubiquitous, affecting the phenotypes of organisms in complex ways. Knowledge about such interactions is becoming rate-limiting for our understanding of human disease and other biological phenomena. Phenomics refers to the integrative analysis of how all genes contribute to phenotype variation, entailing genome and organism level information. A systems biology view of gene interactions is critical for phenomics. Unfortunately the problem is intractable in humans; however, it can be addressed in simpler genetic model systems. Our research group has focused on the concept of genetic buffering of phenotypic variation, in studies employing the single-cell eukaryotic organism, S. cerevisiae. We have developed a methodology, quantitative high throughput cellular phenotyping (Q-HTCP), for high-resolution measurements of gene-gene and gene-environment interactions on a genome-wide scale. Q-HTCP is being applied to the complete set of S. cerevisiae gene deletion strains, a unique resource for systematically mapping gene interactions. Genetic buffering is the idea that comprehensive and quantitative knowledge about how genes interact with respect to phenotypes will lead to an appreciation of how genes and pathways are functionally connected at a systems level to maintain homeostasis. However, extracting biologically useful information from Q-HTCP data is challenging, due to the multidimensional and nonlinear nature of gene interactions, together with a relative lack of prior biological information. Here we describe a new approach for mining quantitative genetic interaction data called recursive expectation-maximization clustering (REMc). We developed REMc to help discover phenomic modules, defined as sets of genes with similar patterns of interaction across a series of genetic or environmental perturbations. Such modules are reflective of buffering mechanisms, i.e., genes that play a related role in the maintenance of physiological homeostasis. To develop the method, 297 gene deletion strains were selected based on gene-drug interactions with hydroxyurea, an inhibitor of ribonucleotide reductase enzyme activity, which is critical for DNA synthesis. To partition the gene functions, these 297 deletion strains were challenged with growth inhibitory drugs known to target different genes and cellular pathways. Q-HTCP-derived growth curves were used to quantify all gene interactions, and the data were used to test the performance of REMc. Fundamental advantages of REMc include objective assessment of total number of clusters and assignment to each cluster a log-likelihood value, which can be considered an indicator of statistical quality of clusters. To assess the biological quality of clusters, we developed a method called gene ontology information divergence z-score (GOid_z). GOid_z summarizes total enrichment of GO attributes within individual clusters. Using these and other criteria, we compared the performance of REMc to hierarchical and K-means clustering. The main conclusion is that REMc provides distinct efficiencies for mining Q-HTCP data. It facilitates identification of phenomic modules, which contribute to buffering mechanisms that underlie cellular homeostasis and the regulation of phenotypic expression.

Cross-Modulated Amplitudes and Frequencies Characterize Interacting Components in Complex Systems

NASA Astrophysics Data System (ADS)

Gans, Fabian; Schumann, Aicko Y.; Kantelhardt, Jan W.; Penzel, Thomas; Fietze, Ingo

2009-03-01

The dynamics of complex systems is characterized by oscillatory components on many time scales. To study the interactions between these components we analyze the cross modulation of their instantaneous amplitudes and frequencies, separating synchronous and antisynchronous modulation. We apply our novel technique to brain-wave oscillations in the human electroencephalogram and show that interactions between the α wave and the δ or β wave oscillators as well as spatial interactions can be quantified and related with physiological conditions (e.g., sleep stages). Our approach overcomes the limitation to oscillations with similar frequencies and enables us to quantify directly nonlinear effects such as positive or negative frequency modulation.

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses

ERIC Educational Resources Information Center

Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, Jeff

2016-01-01

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory…

Narrow linewidth diode laser modules for quantum optical sensor applications in the field and in space

NASA Astrophysics Data System (ADS)

Wicht, A.; Bawamia, A.; Krüger, M.; Kürbis, Ch.; Schiemangk, M.; Smol, R.; Peters, A.; Tränkle, G.

2017-02-01

We present the status of our efforts to develop very compact and robust diode laser modules specifically suited for quantum optics experiments in the field and in space. The paper describes why hybrid micro-integration and GaAs-diode laser technology is best suited to meet the needs of such applications. The electro-optical performance achieved with hybrid micro-integrated, medium linewidth, high power distributed-feedback master-oscillator-power-amplifier modules and with medium power, narrow linewidth extended cavity diode lasers emitting at 767 nm and 780 nm are briefly described and the status of space relevant stress tests and space heritage is summarized. We also describe the performance of an ECDL operating at 1070 nm. Further, a novel and versatile technology platform is introduced that allows for integration of any type of laser system or electro-optical module that can be constructed from two GaAs chips. This facilitates, for the first time, hybrid micro-integration, e.g. of extended cavity diode laser master-oscillator-poweramplifier modules, of dual-stage optical amplifiers, or of lasers with integrated, chip-based phase modulator. As an example we describe the implementation of an ECDL-MOPA designed for experiments on ultra-cold rubidium and potassium atoms on board a sounding rocket and give basic performance parameters.

Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation

DOE PAGES

Mitrea, Diana M.; Cika, Jaclyn A.; Stanley, Christopher B.; ...

2018-02-26

Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid–liquid phase separation (LLPS) via heterotypic interactions with nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), and is integral to the liquid-like nucleolar matrix. Here we show that NPM1 can also undergo LLPS via homotypic interactions between its polyampholytic intrinsically disordered regions, a mechanism that opposes LLPS via heterotypic interactions. Using a combination of biophysical techniques, including confocal microscopy, SAXS, analytical ultracentrifugation, and single-molecule fluorescence, we describe how conformational changes withinmore » NPM1 control valency and switching between the different LLPS mechanisms. We propose that this newly discovered interplay between multiple LLPS mechanisms may influence the direction of vectorial pre-ribosomal particle assembly within, and exit from the nucleolus as part of the ribosome biogenesis process.« less

Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation

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

Mitrea, Diana M.; Cika, Jaclyn A.; Stanley, Christopher B.

Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid–liquid phase separation (LLPS) via heterotypic interactions with nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), and is integral to the liquid-like nucleolar matrix. Here we show that NPM1 can also undergo LLPS via homotypic interactions between its polyampholytic intrinsically disordered regions, a mechanism that opposes LLPS via heterotypic interactions. Using a combination of biophysical techniques, including confocal microscopy, SAXS, analytical ultracentrifugation, and single-molecule fluorescence, we describe how conformational changes withinmore » NPM1 control valency and switching between the different LLPS mechanisms. We propose that this newly discovered interplay between multiple LLPS mechanisms may influence the direction of vectorial pre-ribosomal particle assembly within, and exit from the nucleolus as part of the ribosome biogenesis process.« less

The SH2 domain interaction landscape.

PubMed

Tinti, Michele; Kiemer, Lars; Costa, Stefano; Miller, Martin L; Sacco, Francesca; Olsen, Jesper V; Carducci, Martina; Paoluzi, Serena; Langone, Francesca; Workman, Christopher T; Blom, Nikolaj; Machida, Kazuya; Thompson, Christopher M; Schutkowski, Mike; Brunak, Søren; Mann, Matthias; Mayer, Bruce J; Castagnoli, Luisa; Cesareni, Gianni

2013-04-25

Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Social information influences trust behaviour in adolescents.

PubMed

Lee, Nikki C; Jolles, Jelle; Krabbendam, Lydia

2016-01-01

Trust plays an integral role in daily interactions within adolescents' social environment. Using a trust game paradigm, this study investigated the modulating influence of social information about three interaction partners on trust behaviour in adolescents aged 12-18 (N = 845). After receiving information about their interaction partners prior to the task, participants were most likely to share with a 'good' partner and rate this partner as most trustworthy. Over the course of the task all interaction partners showed similar levels of trustworthy behaviour, but overall participants continued to trust and view the good partner as more trustworthy than 'bad' and 'neutral' partners throughout the game. However, with age the ability to overcome prior social information and adapt trust behaviour improved: middle and late adolescents showed a larger decrease in trust of the good partner than early adolescents, and late adolescents were more likely to reward trustworthy behaviour from the negative partner. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Integrating STEM education through Project-Based Inquiry Learning (PIL) in topic space among year one pupils

NASA Astrophysics Data System (ADS)

Ng, Chee Hoe; Adnan, M.

2018-01-01

This research aims to investigate the effect of integrating STEM education through Project-based Inquiry Learning (PIL) and the users of the STEM modules which consists of five projects on topic Space in Year One Mathematics Syllabus in Kurikulum Standard Sekolah Rendah (KSSR) of Malaysia. STEM education in primary school focuses on the introduces and awareness of students about the importance of STEM education. The projects in STEM modules are covering the different ethnic cultures in Malaysia. The modules are designed using the four phases in PIL. Concepts and the explanation of STEM education on each project are emphasized and provided in the modules so the teachers able to carry out the projects by using the modules. By using the modules in primary Mathematics, the students and teachers will be more understanding on how to integrate the Mathematics’ concepts in STEM education.

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions.

PubMed

Baxter, Robert C

2013-08-01

In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases -8 and -9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNA-dependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and pro-survival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.

Modular biological function is most effectively captured by combining molecular interaction data types.

PubMed

Ames, Ryan M; Macpherson, Jamie I; Pinney, John W; Lovell, Simon C; Robertson, David L

2013-01-01

Large-scale molecular interaction data sets have the potential to provide a comprehensive, system-wide understanding of biological function. Although individual molecules can be promiscuous in terms of their contribution to function, molecular functions emerge from the specific interactions of molecules giving rise to modular organisation. As functions often derive from a range of mechanisms, we demonstrate that they are best studied using networks derived from different sources. Implementing a graph partitioning algorithm we identify subnetworks in yeast protein-protein interaction (PPI), genetic interaction and gene co-regulation networks. Among these subnetworks we identify cohesive subgraphs that we expect to represent functional modules in the different data types. We demonstrate significant overlap between the subgraphs generated from the different data types and show these overlaps can represent related functions as represented by the Gene Ontology (GO). Next, we investigate the correspondence between our subgraphs and the Gene Ontology. This revealed varying degrees of coverage of the biological process, molecular function and cellular component ontologies, dependent on the data type. For example, subgraphs from the PPI show enrichment for 84%, 58% and 93% of annotated GO terms, respectively. Integrating the interaction data into a combined network increases the coverage of GO. Furthermore, the different annotation types of GO are not predominantly associated with one of the interaction data types. Collectively our results demonstrate that successful capture of functional relationships by network data depends on both the specific biological function being characterised and the type of network data being used. We identify functions that require integrated information to be accurately represented, demonstrating the limitations of individual data types. Combining interaction subnetworks across data types is therefore essential for fully understanding the complex and emergent nature of biological function.