Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines.

PubMed

Campbell, Jonathan J; Husmann, Anke; Hume, Robert D; Watson, Christine J; Cameron, Ruth E

2017-01-01

Cancer is characterized by cell heterogeneity and the development of 3D in vitro assays that can distinguish more invasive or migratory phenotypes could enhance diagnosis or drug discovery. 3D collagen scaffolds have been used to develop analogues of complex tissues in vitro and are suited to routine biochemical and immunological assays. We sought to increase 3D model tractability and modulate the migration rate of seeded cells using an ice-templating technique to create either directional/anisotropic or non-directional/isotropic porous architectures within cross-linked collagen scaffolds. Anisotropic scaffolds supported the enhanced migration of an invasive breast cancer cell line MDA-MB-231 with an altered spatial distribution of proliferative cells in contrast to invasive MDA-MB-468 and non-invasive MCF-7 cells lines. In addition, MDA-MB-468 showed increased migration upon epithelial-to-mesenchymal transition (EMT) in anisotropic scaffolds. The provision of controlled architecture in this system may act both to increase assay robustness and as a tuneable parameter to capture detection of a migrated population within a set time, with consequences for primary tumour migration analysis. The separation of invasive clones from a cancer biomass with in vitro platforms could enhance drug development and diagnosis testing by contributing assay metrics including migration rate, as well as modelling cell-cell and cell-matrix interaction in a system compatible with routine histopathological testing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication

PubMed Central

Korithoski, Bryan; Kolaczkowski, Oralia; Mukherjee, Krishanu; Kola, Reema; Earl, Chandra; Kolaczkowski, Bryan

2015-01-01

The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that—in the absence of ubiquitin—it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2). Although the RLRs originated in the earliest animals, both the IPS1 gene and the twin-CARD domain architecture of RIG-I and MDA5 arose much later in the deuterostome lineage, probably through a series of tandem partial-gene duplication events facilitated by tight clustering of RLRs and IPS1 in the ancestral deuterostome genome. Functional differentiation of RIG-I CARD1 and CARD2 appears to have occurred early during this proliferation of RLR and related CARDs, potentially driven by adaptive coevolution between RIG-I CARD domains and IPS1 CARD. However, functional differentiation of MDA5 CARD1 and CARD2 occurred later. These results fit a general model in which duplications of protein-protein interaction domains into novel gene contexts could facilitate the expansion of signaling networks and suggest a potentially important role for functionally-linked gene clusters in generating novel immune-signaling pathways. PMID:26356745

Petri net model for analysis of concurrently processed complex algorithms

NASA Technical Reports Server (NTRS)

Stoughton, John W.; Mielke, Roland R.

1986-01-01

This paper presents a Petri-net model suitable for analyzing the concurrent processing of computationally complex algorithms. The decomposed operations are to be processed in a multiple processor, data driven architecture. Of particular interest is the application of the model to both the description of the data/control flow of a particular algorithm, and to the general specification of the data driven architecture. A candidate architecture is also presented.

CrossTalk. The Journal of Defense Software Engineering. Volume 23, Number 6, Nov/Dec 2010

DTIC Science & Technology

2010-11-01

Model of archi- tectural design. It guides developers to apply effort to their software architecture commensurate with the risks faced by...Driven Model is the promotion of risk to prominence. It is possible to apply the Risk-Driven Model to essentially any software development process...succeed without any planned architecture work, while many high-risk projects would fail without it . The Risk-Driven Model walks a middle path

Colaborated Architechture Framework for Composition UML 2.0 in Zachman Framework

NASA Astrophysics Data System (ADS)

Hermawan; Hastarista, Fika

2016-01-01

Zachman Framework (ZF) is the framework of enterprise architechture that most widely adopted in the Enterprise Information System (EIS) development. In this study, has been developed Colaborated Architechture Framework (CAF) to collaborate ZF with Unified Modeling Language (UML) 2.0 modeling. The CAF provides the composition of ZF matrix that each cell is consist of the Model Driven architechture (MDA) from the various UML models and many Software Requirement Specification (SRS) documents. Implementation of this modeling is used to develops Enterprise Resource Planning (ERP). Because ERP have a coverage of applications in large numbers and complexly relations, it is necessary to use Agile Model Driven Design (AMDD) approach as an advanced method to transforms MDA into components of application modules with efficiently and accurately. Finally, through the using of the CAF, give good achievement in fullfilment the needs from all stakeholders that are involved in the overall process stage of Rational Unified Process (RUP), and also obtaining a high satisfaction to fullfiled the functionality features of the ERP software in PT. Iglas (Persero) Gresik.

Medical Data Architecture (MDA) Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Gurram, M.; Wolfe, S.; Marker, N.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2018-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current in-flight medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are a variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable a more medically autonomous crew than the current paradigm. The medical system requirements are being developed in parallel with the exploration mission architecture and vehicle design. ExMC has recognized that in order to make informed decisions about a medical data architecture framework, current methods for medical data management must not only be understood, but an architecture must also be identified that provides the crew with actionable insight to medical conditions. This medical data architecture will provide the necessary functionality to address the challenges of executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. Hence, the products supported by current prototype development will directly inform exploration medical system requirements.

Mars Sample Return Architecture Assessment Study

NASA Astrophysics Data System (ADS)

Centuori, S.; Hermosín, P.; Martín, J.; De Zaiacomo, G.; Colin, S.; Godfrey, A.; Myles, J.; Johnson, H.; Sachdev, T.; Ahmed, R.

2018-04-01

Current paper presents the results of ESA funded activity "Mars Sample Return Architecture Assessment Study" carried-out by DEIMOS Space, Lockheed Martin UK Ampthill, and MDA Corporation, where more than 500 mission design options have been studied.

Network-driven design principles for neuromorphic systems.

PubMed

Partzsch, Johannes; Schüffny, Rene

2015-01-01

Synaptic connectivity is typically the most resource-demanding part of neuromorphic systems. Commonly, the architecture of these systems is chosen mainly on technical considerations. As a consequence, the potential for optimization arising from the inherent constraints of connectivity models is left unused. In this article, we develop an alternative, network-driven approach to neuromorphic architecture design. We describe methods to analyse performance of existing neuromorphic architectures in emulating certain connectivity models. Furthermore, we show step-by-step how to derive a neuromorphic architecture from a given connectivity model. For this, we introduce a generalized description for architectures with a synapse matrix, which takes into account shared use of circuit components for reducing total silicon area. Architectures designed with this approach are fitted to a connectivity model, essentially adapting to its connection density. They are guaranteeing faithful reproduction of the model on chip, while requiring less total silicon area. In total, our methods allow designers to implement more area-efficient neuromorphic systems and verify usability of the connectivity resources in these systems.

Network-driven design principles for neuromorphic systems

PubMed Central

Partzsch, Johannes; Schüffny, Rene

2015-01-01

Synaptic connectivity is typically the most resource-demanding part of neuromorphic systems. Commonly, the architecture of these systems is chosen mainly on technical considerations. As a consequence, the potential for optimization arising from the inherent constraints of connectivity models is left unused. In this article, we develop an alternative, network-driven approach to neuromorphic architecture design. We describe methods to analyse performance of existing neuromorphic architectures in emulating certain connectivity models. Furthermore, we show step-by-step how to derive a neuromorphic architecture from a given connectivity model. For this, we introduce a generalized description for architectures with a synapse matrix, which takes into account shared use of circuit components for reducing total silicon area. Architectures designed with this approach are fitted to a connectivity model, essentially adapting to its connection density. They are guaranteeing faithful reproduction of the model on chip, while requiring less total silicon area. In total, our methods allow designers to implement more area-efficient neuromorphic systems and verify usability of the connectivity resources in these systems. PMID:26539079

Medical Data Architecture Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Lindsey, A.; Marker, N.; Wolfe, S.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2017-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current International Space Station (ISS) medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable an increasingly autonomous crew than the current ISS paradigm. The MDA will develop capabilities that support automated data collection, and the necessary functionality and challenges in executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. To attain this goal, the first year of the MDA project focused on reducing technical risk, developing documentation and instituting iterative development processes that established the basis for the first version of MDA software (or Test Bed 1). Test Bed 1 is based on a nominal operations scenario authored by the ExMC Element Scientist. This narrative was decomposed into a Concept of Operations that formed the basis for Test Bed 1 requirements. These requirements were successfully vetted through the MDA Test Bed 1 System Requirements Review, which permitted the MDA project to begin software code development and component integration. This paper highlights the MDA objectives, development processes, and accomplishments, and identifies the fiscal year 2017 milestones and deliverables in the upcoming year.

Preliminary Results from a Model-Driven Architecture Methodology for Development of an Event-Driven Space Communications Service Concept

NASA Technical Reports Server (NTRS)

Roberts, Christopher J.; Morgenstern, Robert M.; Israel, David J.; Borky, John M.; Bradley, Thomas H.

2017-01-01

NASA's next generation space communications network will involve dynamic and autonomous services analogous to services provided by current terrestrial wireless networks. This architecture concept, known as the Space Mobile Network (SMN), is enabled by several technologies now in development. A pillar of the SMN architecture is the establishment and utilization of a continuous bidirectional control plane space link channel and a new User Initiated Service (UIS) protocol to enable more dynamic and autonomous mission operations concepts, reduced user space communications planning burden, and more efficient and effective provider network resource utilization. This paper provides preliminary results from the application of model driven architecture methodology to develop UIS. Such an approach is necessary to ensure systematic investigation of several open questions concerning the efficiency, robustness, interoperability, scalability and security of the control plane space link and UIS protocol.

Contextualizing Learning Scenarios According to Different Learning Management Systems

ERIC Educational Resources Information Center

Drira, R.; Laroussi, M.; Le Pallec, X.; Warin, B.

2012-01-01

In this paper, we first demonstrate that an instructional design process of Technology Enhanced Learning (TEL) systems based on a Model Driven Approach (MDA) addresses the limits of Learning Technology Standards (LTS), such as SCORM and IMS-LD. Although these standards ensure the interoperability of TEL systems across different Learning Management…

A Comparison and Evaluation of Real-Time Software Systems Modeling Languages

NASA Technical Reports Server (NTRS)

Evensen, Kenneth D.; Weiss, Kathryn Anne

2010-01-01

A model-driven approach to real-time software systems development enables the conceptualization of software, fostering a more thorough understanding of its often complex architecture and behavior while promoting the documentation and analysis of concerns common to real-time embedded systems such as scheduling, resource allocation, and performance. Several modeling languages have been developed to assist in the model-driven software engineering effort for real-time systems, and these languages are beginning to gain traction with practitioners throughout the aerospace industry. This paper presents a survey of several real-time software system modeling languages, namely the Architectural Analysis and Design Language (AADL), the Unified Modeling Language (UML), Systems Modeling Language (SysML), the Modeling and Analysis of Real-Time Embedded Systems (MARTE) UML profile, and the AADL for UML profile. Each language has its advantages and disadvantages, and in order to adequately describe a real-time software system's architecture, a complementary use of multiple languages is almost certainly necessary. This paper aims to explore these languages in the context of understanding the value each brings to the model-driven software engineering effort and to determine if it is feasible and practical to combine aspects of the various modeling languages to achieve more complete coverage in architectural descriptions. To this end, each language is evaluated with respect to a set of criteria such as scope, formalisms, and architectural coverage. An example is used to help illustrate the capabilities of the various languages.

Enhancement of the Acquisition Process for a Combat System-A Case Study to Model the Workflow Processes for an Air Defense System Acquisition

DTIC Science & Technology

2009-12-01

Business Process Modeling BPMN Business Process Modeling Notation SoA Service-oriented Architecture UML Unified Modeling Language CSP...system developers. Supporting technologies include Business Process Modeling Notation ( BPMN ), Unified Modeling Language (UML), model-driven architecture

A Multilateral Negotiation Model for Cloud Service Market

NASA Astrophysics Data System (ADS)

Yoo, Dongjin; Sim, Kwang Mong

Trading cloud services between consumers and providers is a complicated issue of cloud computing. Since a consumer can negotiate with multiple providers to acquire the same service and each provider can receive many requests from multiple consumers, to facilitate the trading of cloud services among multiple consumers and providers, a multilateral negotiation model for cloud market is necessary. The contribution of this work is the proposal of a business model supporting a multilateral price negotiation for trading cloud services. The design of proposed systems for cloud service market includes considering a many-to-many negotiation protocol, and price determining factor from service level feature. Two negotiation strategies are implemented: 1) MDA (Market Driven Agent); and 2) adaptive concession making responding to changes of bargaining position are proposed for cloud service market. Empirical results shows that MDA achieved better performance in some cases that the adaptive concession making strategy, it is noted that unlike the MDA, the adaptive concession making strategy does not assume that an agent has information of the number of competitors (e.g., a consumer agent adopting the adaptive concession making strategy need not know the number of consumer agents competing for the same service).

The use of geospatial web services for exchanging utilities data

NASA Astrophysics Data System (ADS)

Kuczyńska, Joanna

2013-04-01

Geographic information technologies and related geo-information systems currently play an important role in the management of public administration in Poland. One of these tasks is to maintain and update Geodetic Evidence of Public Utilities (GESUT), part of the National Geodetic and Cartographic Resource, which contains an important for many institutions information of technical infrastructure. It requires an active exchange of data between the Geodesy and Cartography Documentation Centers and institutions, which administrate transmission lines. The administrator of public utilities, is legally obliged to provide information about utilities to GESUT. The aim of the research work was to develop a universal data exchange methodology, which can be implemented on a variety of hardware and software platforms. This methodology use Unified Modeling Language (UML), eXtensible Markup Language (XML), and Geography Markup Language (GML). The proposed methodology is based on the two different strategies: Model Driven Architecture (MDA) and Service Oriented Architecture (SOA). Used solutions are consistent with the INSPIRE Directive and ISO 19100 series standards for geographic information. On the basis of analysis of the input data structures, conceptual models were built for both databases. Models were written in the universal modeling language: UML. Combined model that defines a common data structure was also built. This model was transformed into developed for the exchange of geographic information GML standard. The structure of the document describing the data that may be exchanged is defined in the .xsd file. Network services were selected and implemented in the system designed for data exchange based on open source tools. Methodology was implemented and tested. Data in the agreed data structure and metadata were set up on the server. Data access was provided by geospatial network services: data searching possibilities by Catalog Service for the Web (CSW), data collection by Web Feature Service (WFS). WFS provides also operation for modification data, for example to update them by utility administrator. The proposed solution significantly increases the efficiency of data exchange and facilitates maintenance the National Geodetic and Cartographic Resource.

Data Strategies to Support Automated Multi-Sensor Data Fusion in a Service Oriented Architecture

DTIC Science & Technology

2008-06-01

and employ vast quantities of content. This dissertation provides two software architectural patterns and an auto-fusion process that guide the...UDDI), Simple Order Access Protocol (SOAP), Java, Maritime Domain Awareness (MDA), Business Process Execution Language for Web Service (BPEL4WS) 16...content. This dissertation provides two software architectural patterns and an auto-fusion process that guide the development of a distributed

caCORE version 3: Implementation of a model driven, service-oriented architecture for semantic interoperability.

PubMed

Komatsoulis, George A; Warzel, Denise B; Hartel, Francis W; Shanbhag, Krishnakant; Chilukuri, Ram; Fragoso, Gilberto; Coronado, Sherri de; Reeves, Dianne M; Hadfield, Jillaine B; Ludet, Christophe; Covitz, Peter A

2008-02-01

One of the requirements for a federated information system is interoperability, the ability of one computer system to access and use the resources of another system. This feature is particularly important in biomedical research systems, which need to coordinate a variety of disparate types of data. In order to meet this need, the National Cancer Institute Center for Bioinformatics (NCICB) has created the cancer Common Ontologic Representation Environment (caCORE), an interoperability infrastructure based on Model Driven Architecture. The caCORE infrastructure provides a mechanism to create interoperable biomedical information systems. Systems built using the caCORE paradigm address both aspects of interoperability: the ability to access data (syntactic interoperability) and understand the data once retrieved (semantic interoperability). This infrastructure consists of an integrated set of three major components: a controlled terminology service (Enterprise Vocabulary Services), a standards-based metadata repository (the cancer Data Standards Repository) and an information system with an Application Programming Interface (API) based on Domain Model Driven Architecture. This infrastructure is being leveraged to create a Semantic Service-Oriented Architecture (SSOA) for cancer research by the National Cancer Institute's cancer Biomedical Informatics Grid (caBIG).

caCORE version 3: Implementation of a model driven, service-oriented architecture for semantic interoperability

PubMed Central

Komatsoulis, George A.; Warzel, Denise B.; Hartel, Frank W.; Shanbhag, Krishnakant; Chilukuri, Ram; Fragoso, Gilberto; de Coronado, Sherri; Reeves, Dianne M.; Hadfield, Jillaine B.; Ludet, Christophe; Covitz, Peter A.

2008-01-01

One of the requirements for a federated information system is interoperability, the ability of one computer system to access and use the resources of another system. This feature is particularly important in biomedical research systems, which need to coordinate a variety of disparate types of data. In order to meet this need, the National Cancer Institute Center for Bioinformatics (NCICB) has created the cancer Common Ontologic Representation Environment (caCORE), an interoperability infrastructure based on Model Driven Architecture. The caCORE infrastructure provides a mechanism to create interoperable biomedical information systems. Systems built using the caCORE paradigm address both aspects of interoperability: the ability to access data (syntactic interoperability) and understand the data once retrieved (semantic interoperability). This infrastructure consists of an integrated set of three major components: a controlled terminology service (Enterprise Vocabulary Services), a standards-based metadata repository (the cancer Data Standards Repository) and an information system with an Application Programming Interface (API) based on Domain Model Driven Architecture. This infrastructure is being leveraged to create a Semantic Service Oriented Architecture (SSOA) for cancer research by the National Cancer Institute’s cancer Biomedical Informatics Grid (caBIG™). PMID:17512259

Semantic Web-Driven LMS Architecture towards a Holistic Learning Process Model Focused on Personalization

ERIC Educational Resources Information Center

Kerkiri, Tania

2010-01-01

A comprehensive presentation is here made on the modular architecture of an e-learning platform with a distinctive emphasis on content personalization, combining advantages from semantic web technology, collaborative filtering and recommendation systems. Modules of this architecture handle information about both the domain-specific didactic…

Strategies for concurrent processing of complex algorithms in data driven architectures

NASA Technical Reports Server (NTRS)

Stoughton, John W.; Mielke, Roland R.

1988-01-01

The purpose is to document research to develop strategies for concurrent processing of complex algorithms in data driven architectures. The problem domain consists of decision-free algorithms having large-grained, computationally complex primitive operations. Such are often found in signal processing and control applications. The anticipated multiprocessor environment is a data flow architecture containing between two and twenty computing elements. Each computing element is a processor having local program memory, and which communicates with a common global data memory. A new graph theoretic model called ATAMM which establishes rules for relating a decomposed algorithm to its execution in a data flow architecture is presented. The ATAMM model is used to determine strategies to achieve optimum time performance and to develop a system diagnostic software tool. In addition, preliminary work on a new multiprocessor operating system based on the ATAMM specifications is described.

Model-Driven Development of Safety Architectures

NASA Technical Reports Server (NTRS)

Denney, Ewen; Pai, Ganesh; Whiteside, Iain

2017-01-01

We describe the use of model-driven development for safety assurance of a pioneering NASA flight operation involving a fleet of small unmanned aircraft systems (sUAS) flying beyond visual line of sight. The central idea is to develop a safety architecture that provides the basis for risk assessment and visualization within a safety case, the formal justification of acceptable safety required by the aviation regulatory authority. A safety architecture is composed from a collection of bow tie diagrams (BTDs), a practical approach to manage safety risk by linking the identified hazards to the appropriate mitigation measures. The safety justification for a given unmanned aircraft system (UAS) operation can have many related BTDs. In practice, however, each BTD is independently developed, which poses challenges with respect to incremental development, maintaining consistency across different safety artifacts when changes occur, and in extracting and presenting stakeholder specific information relevant for decision making. We show how a safety architecture reconciles the various BTDs of a system, and, collectively, provide an overarching picture of system safety, by considering them as views of a unified model. We also show how it enables model-driven development of BTDs, replete with validations, transformations, and a range of views. Our approach, which we have implemented in our toolset, AdvoCATE, is illustrated with a running example drawn from a real UAS safety case. The models and some of the innovations described here were instrumental in successfully obtaining regulatory flight approval.

Strategies for concurrent processing of complex algorithms in data driven architectures

NASA Technical Reports Server (NTRS)

Stoughton, John W.; Mielke, Roland R.

1988-01-01

Research directed at developing a graph theoretical model for describing data and control flow associated with the execution of large grained algorithms in a special distributed computer environment is presented. This model is identified by the acronym ATAMM which represents Algorithms To Architecture Mapping Model. The purpose of such a model is to provide a basis for establishing rules for relating an algorithm to its execution in a multiprocessor environment. Specifications derived from the model lead directly to the description of a data flow architecture which is a consequence of the inherent behavior of the data and control flow described by the model. The purpose of the ATAMM based architecture is to provide an analytical basis for performance evaluation. The ATAMM model and architecture specifications are demonstrated on a prototype system for concept validation.

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

Riensche, Roderick M.; Paulson, Patrick R.; Danielson, Gary R.

We describe a methodology and architecture to support the development of games in a predictive analytics context. These games serve as part of an overall family of systems designed to gather input knowledge, calculate results of complex predictive technical and social models, and explore those results in an engaging fashion. The games provide an environment shaped and driven in part by the outputs of the models, allowing users to exert influence over a limited set of parameters, and displaying the results when those actions cause changes in the underlying model. We have crafted a prototype system in which we aremore » implementing test versions of games driven by models in such a fashion, using a flexible architecture to allow for future continuation and expansion of this work.« less

Medical Data Architecture Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Gurram, M.; Wolfe, S.; Marker, N.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2018-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current in-flight medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are a variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable a more medically autonomous crew than the current paradigm. The medical system requirements are being developed in parallel with the exploration mission architecture and vehicle design. ExMC has recognized that in order to make informed decisions about a medical data architecture framework, current methods for medical data management must not only be understood, but an architecture must also be identified that provides the crew with actionable insight to medical conditions. This medical data architecture will provide the necessary functionality to address the challenges of executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. Hence, the products supported by current prototype development will directly inform exploration medical system requirements.

Strategies for concurrent processing of complex algorithms in data driven architectures

NASA Technical Reports Server (NTRS)

Stoughton, John W.; Mielke, Roland R.

1987-01-01

The results of ongoing research directed at developing a graph theoretical model for describing data and control flow associated with the execution of large grained algorithms in a spatial distributed computer environment is presented. This model is identified by the acronym ATAMM (Algorithm/Architecture Mapping Model). The purpose of such a model is to provide a basis for establishing rules for relating an algorithm to its execution in a multiprocessor environment. Specifications derived from the model lead directly to the description of a data flow architecture which is a consequence of the inherent behavior of the data and control flow described by the model. The purpose of the ATAMM based architecture is to optimize computational concurrency in the multiprocessor environment and to provide an analytical basis for performance evaluation. The ATAMM model and architecture specifications are demonstrated on a prototype system for concept validation.

Atomic structure of the Y complex of the nuclear pore

DOE PAGES

Kelley, Kotaro; Knockenhauer, Kevin E.; Kabachinski, Greg; ...

2015-03-30

The nuclear pore complex (NPC) is the principal gateway for transport into and out of the nucleus. Selectivity is achieved through the hydrogel-like core of the NPC. The structural integrity of the NPC depends on ~15 architectural proteins, which are organized in distinct subcomplexes to form the >40-MDa ring-like structure. In this paper, we present the 4.1-Å crystal structure of a heterotetrameric core element ('hub') of the Y complex, the essential NPC building block, from Myceliophthora thermophila. Using the hub structure together with known Y-complex fragments, we built the entire ~0.5-MDa Y complex. Our data reveal that the conserved coremore » of the Y complex has six rather than seven members. Finally, evolutionarily distant Y-complex assemblies share a conserved core that is very similar in shape and dimension, thus suggesting that there are closely related architectural codes for constructing the NPC in all eukaryotes.« less

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP.

PubMed

Shim, Yoonsik; Philippides, Andrew; Staras, Kevin; Husbands, Phil

2016-10-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture.

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP

PubMed Central

Staras, Kevin

2016-01-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture. PMID:27760125

Managing business compliance using model-driven security management

NASA Astrophysics Data System (ADS)

Lang, Ulrich; Schreiner, Rudolf

Compliance with regulatory and governance standards is rapidly becoming one of the hot topics of information security today. This is because, especially with regulatory compliance, both business and government have to expect large financial and reputational losses if compliance cannot be ensured and demonstrated. One major difficulty of implementing such regulations is caused the fact that they are captured at a high level of abstraction that is business-centric and not IT centric. This means that the abstract intent needs to be translated in a trustworthy, traceable way into compliance and security policies that the IT security infrastructure can enforce. Carrying out this mapping process manually is time consuming, maintenance-intensive, costly, and error-prone. Compliance monitoring is also critical in order to be able to demonstrate compliance at any given point in time. The problem is further complicated because of the need for business-driven IT agility, where IT policies and enforcement can change frequently, e.g. Business Process Modelling (BPM) driven Service Oriented Architecture (SOA). Model Driven Security (MDS) is an innovative technology approach that can solve these problems as an extension of identity and access management (IAM) and authorization management (also called entitlement management). In this paper we will illustrate the theory behind Model Driven Security for compliance, provide an improved and extended architecture, as well as a case study in the healthcare industry using our OpenPMF 2.0 technology.

Differential nuclear shape dynamics of invasive andnon-invasive breast cancer cells are associated with actin cytoskeleton organization and stability.

PubMed

Chiotaki, Rena; Polioudaki, Hara; Theodoropoulos, Panayiotis A

2014-08-01

Cancer cells often exhibit characteristic aberrations in their nuclear architecture, which are indicative of their malignant potential. In this study, we have examined the nuclear and cytoskeletal composition, attachment configuration dynamics, and osmotic or drug treatment response of invasive (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive nuclear elasticity and deformability and displayed distinct kinetic profiles during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour malformations following actin reorganization.

Pharmacokinetic modeling of 4,4'-methylenedianiline released from reused polyurethane dialyzer potting materials.

PubMed

Do Luu, H M; Hutter, J C

2000-01-01

4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of (14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time. Copyright 2000 John Wiley & Sons, Inc.

Functional language and data flow architectures

NASA Technical Reports Server (NTRS)

Ercegovac, M. D.; Patel, D. R.; Lang, T.

1983-01-01

This is a tutorial article about language and architecture approaches for highly concurrent computer systems based on the functional style of programming. The discussion concentrates on the basic aspects of functional languages, and sequencing models such as data-flow, demand-driven and reduction which are essential at the machine organization level. Several examples of highly concurrent machines are described.

A generative tool for building health applications driven by ISO 13606 archetypes.

PubMed

Menárguez-Tortosa, Marcos; Martínez-Costa, Catalina; Fernández-Breis, Jesualdo Tomás

2012-10-01

The use of Electronic Healthcare Records (EHR) standards in the development of healthcare applications is crucial for achieving the semantic interoperability of clinical information. Advanced EHR standards make use of the dual model architecture, which provides a solution for clinical interoperability based on the separation of the information and knowledge. However, the impact of such standards is biased by the limited availability of tools that facilitate their usage and practical implementation. In this paper, we present an approach for the automatic generation of clinical applications for the ISO 13606 EHR standard, which is based on the dual model architecture. This generator has been generically designed, so it can be easily adapted to other dual model standards and can generate applications for multiple technological platforms. Such good properties are based on the combination of standards for the representation of generic user interfaces and model-driven engineering techniques.

Strategies for concurrent processing of complex algorithms in data driven architectures

NASA Technical Reports Server (NTRS)

Stoughton, John W.; Mielke, Roland R.; Som, Sukhamony

1990-01-01

The performance modeling and enhancement for periodic execution of large-grain, decision-free algorithms in data flow architectures is examined. Applications include real-time implementation of control and signal processing algorithms where performance is required to be highly predictable. The mapping of algorithms onto the specified class of data flow architectures is realized by a marked graph model called ATAMM (Algorithm To Architecture Mapping Model). Performance measures and bounds are established. Algorithm transformation techniques are identified for performance enhancement and reduction of resource (computing element) requirements. A systematic design procedure is described for generating operating conditions for predictable performance both with and without resource constraints. An ATAMM simulator is used to test and validate the performance prediction by the design procedure. Experiments on a three resource testbed provide verification of the ATAMM model and the design procedure.

Strategies for concurrent processing of complex algorithms in data driven architectures

NASA Technical Reports Server (NTRS)

Som, Sukhamoy; Stoughton, John W.; Mielke, Roland R.

1990-01-01

Performance modeling and performance enhancement for periodic execution of large-grain, decision-free algorithms in data flow architectures are discussed. Applications include real-time implementation of control and signal processing algorithms where performance is required to be highly predictable. The mapping of algorithms onto the specified class of data flow architectures is realized by a marked graph model called algorithm to architecture mapping model (ATAMM). Performance measures and bounds are established. Algorithm transformation techniques are identified for performance enhancement and reduction of resource (computing element) requirements. A systematic design procedure is described for generating operating conditions for predictable performance both with and without resource constraints. An ATAMM simulator is used to test and validate the performance prediction by the design procedure. Experiments on a three resource testbed provide verification of the ATAMM model and the design procedure.

Structure and assembly of scalable porous protein cages

NASA Astrophysics Data System (ADS)

Sasaki, Eita; Böhringer, Daniel; van de Waterbeemd, Michiel; Leibundgut, Marc; Zschoche, Reinhard; Heck, Albert J. R.; Ban, Nenad; Hilvert, Donald

2017-03-01

Proteins that self-assemble into regular shell-like polyhedra are useful, both in nature and in the laboratory, as molecular containers. Here we describe cryo-electron microscopy (EM) structures of two versatile encapsulation systems that exploit engineered electrostatic interactions for cargo loading. We show that increasing the number of negative charges on the lumenal surface of lumazine synthase, a protein that naturally assembles into a ~1-MDa dodecahedron composed of 12 pentamers, induces stepwise expansion of the native protein shell, giving rise to thermostable ~3-MDa and ~6-MDa assemblies containing 180 and 360 subunits, respectively. Remarkably, these expanded particles assume unprecedented tetrahedrally and icosahedrally symmetric structures constructed entirely from pentameric units. Large keyhole-shaped pores in the shell, not present in the wild-type capsid, enable diffusion-limited encapsulation of complementarily charged guests. The structures of these supercharged assemblies demonstrate how programmed electrostatic effects can be effectively harnessed to tailor the architecture and properties of protein cages.

Key design elements of a data utility for national biosurveillance: event-driven architecture, caching, and Web service model.

PubMed

Tsui, Fu-Chiang; Espino, Jeremy U; Weng, Yan; Choudary, Arvinder; Su, Hoah-Der; Wagner, Michael M

2005-01-01

The National Retail Data Monitor (NRDM) has monitored over-the-counter (OTC) medication sales in the United States since December 2002. The NRDM collects data from over 18,600 retail stores and processes over 0.6 million sales records per day. This paper describes key architectural features that we have found necessary for a data utility component in a national biosurveillance system. These elements include event-driven architecture to provide analyses of data in near real time, multiple levels of caching to improve query response time, high availability through the use of clustered servers, scalable data storage through the use of storage area networks and a web-service function for interoperation with affiliated systems. The methods and architectural principles are relevant to the design of any production data utility for public health surveillance-systems that collect data from multiple sources in near real time for use by analytic programs and user interfaces that have substantial requirements for time-series data aggregated in multiple dimensions.

Virtual Sensor Web Architecture

NASA Astrophysics Data System (ADS)

Bose, P.; Zimdars, A.; Hurlburt, N.; Doug, S.

2006-12-01

NASA envisions the development of smart sensor webs, intelligent and integrated observation network that harness distributed sensing assets, their associated continuous and complex data sets, and predictive observation processing mechanisms for timely, collaborative hazard mitigation and enhanced science productivity and reliability. This paper presents Virtual Sensor Web Infrastructure for Collaborative Science (VSICS) Architecture for sustained coordination of (numerical and distributed) model-based processing, closed-loop resource allocation, and observation planning. VSICS's key ideas include i) rich descriptions of sensors as services based on semantic markup languages like OWL and SensorML; ii) service-oriented workflow composition and repair for simple and ensemble models; event-driven workflow execution based on event-based and distributed workflow management mechanisms; and iii) development of autonomous model interaction management capabilities providing closed-loop control of collection resources driven by competing targeted observation needs. We present results from initial work on collaborative science processing involving distributed services (COSEC framework) that is being extended to create VSICS.

Hybrid Architectural Framework for C4ISR and Discrete-Event Simulation (DES) to Support Sensor-Driven Model Synthesis in Real-World Scenarios

DTIC Science & Technology

2013-09-01

which utilizes FTA and then loads it into a DES engine to generate simulation results. .......44 Figure 21. This simulation architecture is...While Discrete Event Simulation ( DES ) can provide accurate time estimation and fast simulation speed, models utilizing it often suffer...C4ISR progress in MDW is developed in this research to demonstrate the feasibility of AEMF- DES and explore its potential. The simulation (MDSIM

Notification Event Architecture for Traveler Screening: Predictive Traveler Screening Using Event Driven Business Process Management

ERIC Educational Resources Information Center

Lynch, John Kenneth

2013-01-01

Using an exploratory model of the 9/11 terrorists, this research investigates the linkages between Event Driven Business Process Management (edBPM) and decision making. Although the literature on the role of technology in efficient and effective decision making is extensive, research has yet to quantify the benefit of using edBPM to aid the…

Composable Framework Support for Software-FMEA Through Model Execution

NASA Astrophysics Data System (ADS)

Kocsis, Imre; Patricia, Andras; Brancati, Francesco; Rossi, Francesco

2016-08-01

Performing Failure Modes and Effect Analysis (FMEA) during software architecture design is becoming a basic requirement in an increasing number of domains; however, due to the lack of standardized early design phase model execution, classic SW-FMEA approaches carry significant risks and are human effort-intensive even in processes that use Model-Driven Engineering.Recently, modelling languages with standardized executable semantics have emerged. Building on earlier results, this paper describes framework support for generating executable error propagation models from such models during software architecture design. The approach carries the promise of increased precision, decreased risk and more automated execution for SW-FMEA during dependability- critical system development.

An Object Oriented Extensible Architecture for Affordable Aerospace Propulsion Systems

NASA Technical Reports Server (NTRS)

Follen, Gregory J.

2003-01-01

Driven by a need to explore and develop propulsion systems that exceeded current computing capabilities, NASA Glenn embarked on a novel strategy leading to the development of an architecture that enables propulsion simulations never thought possible before. Full engine 3 Dimensional Computational Fluid Dynamic propulsion system simulations were deemed impossible due to the impracticality of the hardware and software computing systems required. However, with a software paradigm shift and an embracing of parallel and distributed processing, an architecture was designed to meet the needs of future propulsion system modeling. The author suggests that the architecture designed at the NASA Glenn Research Center for propulsion system modeling has potential for impacting the direction of development of affordable weapons systems currently under consideration by the Applied Vehicle Technology Panel (AVT).

Framework for a clinical information system.

PubMed

Van De Velde, R; Lansiers, R; Antonissen, G

2002-01-01

The design and implementation of Clinical Information System architecture is presented. This architecture has been developed and implemented based on components following a strong underlying conceptual and technological model. Common Object Request Broker and n-tier technology featuring centralised and departmental clinical information systems as the back-end store for all clinical data are used. Servers located in the "middle" tier apply the clinical (business) model and application rules. The main characteristics are the focus on modelling and reuse of both data and business logic. Scalability as well as adaptability to constantly changing requirements via component driven computing are the main reasons for that approach.

Robotic assembly and maintenance of future space stations based on the ISS mission operations experience

NASA Astrophysics Data System (ADS)

Rembala, Richard; Ower, Cameron

2009-10-01

MDA has provided 25 years of real-time engineering support to Shuttle (Canadarm) and ISS (Canadarm2) robotic operations beginning with the second shuttle flight STS-2 in 1981. In this capacity, our engineering support teams have become familiar with the evolution of mission planning and flight support practices for robotic assembly and support operations at mission control. This paper presents observations on existing practices and ideas to achieve reduced operational overhead to present programs. It also identifies areas where robotic assembly and maintenance of future space stations and space-based facilities could be accomplished more effectively and efficiently. Specifically, our experience shows that past and current space Shuttle and ISS assembly and maintenance operations have used the approach of extensive preflight mission planning and training to prepare the flight crews for the entire mission. This has been driven by the overall communication latency between the earth and remote location of the space station/vehicle as well as the lack of consistent robotic and interface standards. While the early Shuttle and ISS architectures included robotics, their eventual benefits on the overall assembly and maintenance operations could have been greater through incorporating them as a major design driver from the beginning of the system design. Lessons learned from the ISS highlight the potential benefits of real-time health monitoring systems, consistent standards for robotic interfaces and procedures and automated script-driven ground control in future space station assembly and logistics architectures. In addition, advances in computer vision systems and remote operation, supervised autonomous command and control systems offer the potential to adjust the balance between assembly and maintenance tasks performed using extra vehicular activity (EVA), extra vehicular robotics (EVR) and EVR controlled from the ground, offloading the EVA astronaut and even the robotic operator on-orbit of some of the more routine tasks. Overall these proposed approaches when used effectively offer the potential to drive down operations overhead and allow more efficient and productive robotic operations.

Automated UAV-based video exploitation using service oriented architecture framework

NASA Astrophysics Data System (ADS)

Se, Stephen; Nadeau, Christian; Wood, Scott

2011-05-01

Airborne surveillance and reconnaissance are essential for successful military missions. Such capabilities are critical for troop protection, situational awareness, mission planning, damage assessment, and others. Unmanned Aerial Vehicles (UAVs) gather huge amounts of video data but it is extremely labour-intensive for operators to analyze hours and hours of received data. At MDA, we have developed a suite of tools that can process the UAV video data automatically, including mosaicking, change detection and 3D reconstruction, which have been integrated within a standard GIS framework. In addition, the mosaicking and 3D reconstruction tools have also been integrated in a Service Oriented Architecture (SOA) framework. The Visualization and Exploitation Workstation (VIEW) integrates 2D and 3D visualization, processing, and analysis capabilities developed for UAV video exploitation. Visualization capabilities are supported through a thick-client Graphical User Interface (GUI), which allows visualization of 2D imagery, video, and 3D models. The GUI interacts with the VIEW server, which provides video mosaicking and 3D reconstruction exploitation services through the SOA framework. The SOA framework allows multiple users to perform video exploitation by running a GUI client on the operator's computer and invoking the video exploitation functionalities residing on the server. This allows the exploitation services to be upgraded easily and allows the intensive video processing to run on powerful workstations. MDA provides UAV services to the Canadian and Australian forces in Afghanistan with the Heron, a Medium Altitude Long Endurance (MALE) UAV system. On-going flight operations service provides important intelligence, surveillance, and reconnaissance information to commanders and front-line soldiers.

A task-based support architecture for developing point-of-care clinical decision support systems for the emergency department.

PubMed

Wilk, S; Michalowski, W; O'Sullivan, D; Farion, K; Sayyad-Shirabad, J; Kuziemsky, C; Kukawka, B

2013-01-01

The purpose of this study was to create a task-based support architecture for developing clinical decision support systems (CDSSs) that assist physicians in making decisions at the point-of-care in the emergency department (ED). The backbone of the proposed architecture was established by a task-based emergency workflow model for a patient-physician encounter. The architecture was designed according to an agent-oriented paradigm. Specifically, we used the O-MaSE (Organization-based Multi-agent System Engineering) method that allows for iterative translation of functional requirements into architectural components (e.g., agents). The agent-oriented paradigm was extended with ontology-driven design to implement ontological models representing knowledge required by specific agents to operate. The task-based architecture allows for the creation of a CDSS that is aligned with the task-based emergency workflow model. It facilitates decoupling of executable components (agents) from embedded domain knowledge (ontological models), thus supporting their interoperability, sharing, and reuse. The generic architecture was implemented as a pilot system, MET3-AE--a CDSS to help with the management of pediatric asthma exacerbation in the ED. The system was evaluated in a hospital ED. The architecture allows for the creation of a CDSS that integrates support for all tasks from the task-based emergency workflow model, and interacts with hospital information systems. Proposed architecture also allows for reusing and sharing system components and knowledge across disease-specific CDSSs.

Key Design Elements of a Data Utility for National Biosurveillance: Event-driven Architecture, Caching, and Web Service Model

PubMed Central

Tsui, Fu-Chiang; Espino, Jeremy U.; Weng, Yan; Choudary, Arvinder; Su, Hoah-Der; Wagner, Michael M.

2005-01-01

The National Retail Data Monitor (NRDM) has monitored over-the-counter (OTC) medication sales in the United States since December 2002. The NRDM collects data from over 18,600 retail stores and processes over 0.6 million sales records per day. This paper describes key architectural features that we have found necessary for a data utility component in a national biosurveillance system. These elements include event-driven architecture to provide analyses of data in near real time, multiple levels of caching to improve query response time, high availability through the use of clustered servers, scalable data storage through the use of storage area networks and a web-service function for interoperation with affiliated systems. The methods and architectural principles are relevant to the design of any production data utility for public health surveillance—systems that collect data from multiple sources in near real time for use by analytic programs and user interfaces that have substantial requirements for time-series data aggregated in multiple dimensions. PMID:16779138

A CSP-Based Agent Modeling Framework for the Cougaar Agent-Based Architecture

NASA Technical Reports Server (NTRS)

Gracanin, Denis; Singh, H. Lally; Eltoweissy, Mohamed; Hinchey, Michael G.; Bohner, Shawn A.

2005-01-01

Cognitive Agent Architecture (Cougaar) is a Java-based architecture for large-scale distributed agent-based applications. A Cougaar agent is an autonomous software entity with behaviors that represent a real-world entity (e.g., a business process). A Cougaar-based Model Driven Architecture approach, currently under development, uses a description of system's functionality (requirements) to automatically implement the system in Cougaar. The Communicating Sequential Processes (CSP) formalism is used for the formal validation of the generated system. Two main agent components, a blackboard and a plugin, are modeled as CSP processes. A set of channels represents communications between the blackboard and individual plugins. The blackboard is represented as a CSP process that communicates with every agent in the collection. The developed CSP-based Cougaar modeling framework provides a starting point for a more complete formal verification of the automatically generated Cougaar code. Currently it is used to verify the behavior of an individual agent in terms of CSP properties and to analyze the corresponding Cougaar society.

A model-driven approach for representing clinical archetypes for Semantic Web environments.

PubMed

Martínez-Costa, Catalina; Menárguez-Tortosa, Marcos; Fernández-Breis, Jesualdo Tomás; Maldonado, José Alberto

2009-02-01

The life-long clinical information of any person supported by electronic means configures his Electronic Health Record (EHR). This information is usually distributed among several independent and heterogeneous systems that may be syntactically or semantically incompatible. There are currently different standards for representing and exchanging EHR information among different systems. In advanced EHR approaches, clinical information is represented by means of archetypes. Most of these approaches use the Archetype Definition Language (ADL) to specify archetypes. However, ADL has some drawbacks when attempting to perform semantic activities in Semantic Web environments. In this work, Semantic Web technologies are used to specify clinical archetypes for advanced EHR architectures. The advantages of using the Ontology Web Language (OWL) instead of ADL are described and discussed in this work. Moreover, a solution combining Semantic Web and Model-driven Engineering technologies is proposed to transform ADL into OWL for the CEN EN13606 EHR architecture.

Using Data-Driven Model-Brain Mappings to Constrain Formal Models of Cognition

PubMed Central

Borst, Jelmer P.; Nijboer, Menno; Taatgen, Niels A.; van Rijn, Hedderik; Anderson, John R.

2015-01-01

In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-based biases. In this paper we used model-based fMRI analysis to create a data-driven model-brain mapping for five modules of the ACT-R cognitive architecture. We then validated this mapping by applying it to two new datasets with associated models. The new mapping was at least as powerful as an existing mapping that was based on the literature, and indicated where the models were supported by the data and where they have to be improved. We conclude that data-driven model-brain mappings can provide strong constraints on cognitive models, and that model-based fMRI is a suitable way to create such mappings. PMID:25747601

The relationship of prenatal maternal depression or anxiety to maternal caregiving behavior and infant behavior self-regulation during infant heel lance: an ethological time-based study of behavior.

PubMed

Warnock, Fay F; Craig, Kenneth D; Bakeman, Roger; Castral, Thaila; Mirlashari, Jila

2016-09-07

Sensitive and responsive maternal caregiving behavior strengthens infant self-regulatory capacities (HL), but this regulatory role may be diminished in some mothers with second-trimester prenatal exposure to depression and/ or anxiety (MDA). This study examined maternal and infant behavior during infant heel lance (HL) when mothers had or did not have MDA. Ethological methods and micro-analytic approaches capable of distinguishing and comparing time-based patterning in maternal and infant behavior were used to clarify biological mechanisms, such as MDA, that may underlie observed behavior. Aims were to examine group differences in caregiving behavior between mothers with and without MDA 5 min Pre-HL and 5 min Post-H, and relationships between MDA, maternal caregiving behavior and infant pain behavior self-regulation, concurrently. At second trimester, mothers were assessed for symptoms of mild-severe depression or anxiety. Mothers whose scores exceeded predetermined cut-off scores on one or more of the mental health measures were allocated to the MDA-exposure group, those below to the non-MDA-exposure group. Reliable observers, blinded to MDA status and study phases, coded video records of the caregiving behavior of each study mother for the full duration of the 5 min Pre-HL and 5 min Post-HL study phases. Group differences and associations between mean measures of maternal mental health scores, time-based measures of maternal behavior, and time-based measures of infant pain behavior regulation (previously coded) were concurrently analyzed using comparative and correlational statistics. MDA-exposed mothers spent significantly more time not embracing, engaging or responding to infant cues than maternal controls Pre-HL and Post-HL. MDA was associated with atypical maternal caregiving behavior, which in turn was related to atypical infant pain behavior self-regulation during and after the HL. Our findings have implication for practice. We recommend inclusion of mothers with MDA and their infants in interventions that strengthen the early mother-infant interaction and mother's regulatory caregiving role. MDA and maternal caregiving behavior must be considered in future infant pain studies to examine if they confound effectiveness of mother driven caregiving interventions for neonatal pain. We highlight the importance of examining maternal mental health throughout the perinatal and postnatal trajectory, and particularly the newborn period.

Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD.

PubMed

Grande-García, Araceli; Lallous, Nada; Díaz-Tejada, Celsa; Ramón-Maiques, Santiago

2014-02-04

Upregulation of CAD, the multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidines in animals, is essential for cell proliferation. Deciphering the architecture and functioning of CAD is of interest for its potential usage as an antitumoral target. However, there is no detailed structural information about CAD other than that it self-assembles into hexamers of ∼1.5 MDa. Here we report the crystal structure and functional characterization of the dihydroorotase domain of human CAD. Contradicting all assumptions, the structure reveals an active site enclosed by a flexible loop with two Zn²⁺ ions bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate ion. Site-directed mutagenesis and functional assays prove the involvement of the Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes supports a reclassification of the DHOase family and provides strong evidence against current models of the architecture of CAD. Copyright © 2014 Elsevier Ltd. All rights reserved.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

PubMed

Verver, Suzanne; Walker, Martin; Kim, Young Eun; Fobi, Grace; Tekle, Afework H; Zouré, Honorat G M; Wanji, Samuel; Boakye, Daniel A; Kuesel, Annette C; de Vlas, Sake J; Boussinesq, Michel; Basáñez, Maria-Gloria; Stolk, Wilma A

2018-06-01

Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

PubMed Central

de Vlas, Sake J.; Fischer, Peter U.; Weil, Gary J.; Goldman, Ann S.

2013-01-01

The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020. PMID:23301115

Unusual varieties and duplication of Rig-I like receptors encoded in the marine mollusk, Crassostrea gigas

NASA Astrophysics Data System (ADS)

Tian, Z. H.; Jiao, C. Z.

2017-07-01

RIG-I like receptors (RLRs) play key roles in sensing non-self nucleic acids in cytoplasm and trigger antiviral innate immune response in vertebrates and human body. Here we carried out in silico analysis to identify and investigate the putative RLRs encoded in the genome of marine mollusk, Crassostrea gigas (cgRLRs), an invertebrate species. We found the unusual duplication and varieties on domain architecture of putative cgRLRs encoded in the genome of C. gigas. Three putative cgRLRs (accessions numbers are EKC24603, EKC31344.1 and EKC38304.1 on GenBank), have the similar domain architecture with that of human RIG-I or MDA5, and one protein (EKC34573.1) with that of human LGP2; The fifth putative cgRLRs (EKC38303.1) is somewhat similar with human RIG-I/MDA5 except that it has only one caspase activation and recruitment domain (CARD) in its N-terminal. Other nine proteins were identified to be partialy similar with RLRs while with the incomplete sequences, which maybe reflect the events of partial duplication of cgRLRs genes occurred in the oyster genome.

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.

PubMed

Gabor, K A; Charette, J R; Pietraszewski, M J; Wingfield, D J; Shim, J S; Millard, P J; Kim, C H

2015-08-01

Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrating geo web services for a user driven exploratory analysis

NASA Astrophysics Data System (ADS)

Moncrieff, Simon; Turdukulov, Ulanbek; Gulland, Elizabeth-Kate

2016-04-01

In data exploration, several online data sources may need to be dynamically aggregated or summarised over spatial region, time interval, or set of attributes. With respect to thematic data, web services are mainly used to present results leading to a supplier driven service model limiting the exploration of the data. In this paper we propose a user need driven service model based on geo web processing services. The aim of the framework is to provide a method for the scalable and interactive access to various geographic data sources on the web. The architecture combines a data query, processing technique and visualisation methodology to rapidly integrate and visually summarise properties of a dataset. We illustrate the environment on a health related use case that derives Age Standardised Rate - a dynamic index that needs integration of the existing interoperable web services of demographic data in conjunction with standalone non-spatial secure database servers used in health research. Although the example is specific to the health field, the architecture and the proposed approach are relevant and applicable to other fields that require integration and visualisation of geo datasets from various web services and thus, we believe is generic in its approach.

Quantifying the Contribution of Thermally Driven Recirculation to a High-Ozone Event Along the Colorado Front Range Using Lidar

NASA Technical Reports Server (NTRS)

Sullivan, John T.; McGee, Thomas J.; Langford, Andrew O.; Alvarez, Raul J., II; Senff, Christoph; Reddy, Patrick J.; Thompson, Anne M.; Twigg, Laurence W.; Sumnicht, Grant K.; Lee, Pius;

Maritime domain awareness community of interest net centric information sharing

NASA Astrophysics Data System (ADS)

Andress, Mark; Freeman, Brian; Rhiddlehover, Trey; Shea, John

2007-04-01

This paper highlights the approach taken by the Maritime Domain Awareness (MDA) Community of Interest (COI) in establishing an approach to data sharing that seeks to overcome many of the obstacles to sharing both within the federal government and with international and private sector partners. The approach uses the DOD Net Centric Data Strategy employed through Net Centric Enterprise Services (NCES) Service Oriented Architecture (SOA) foundation provided by Defense Information Systems Agency (DISA), but is unique in that the community is made up of more than just Defense agencies. For the first pilot project, the MDA COI demonstrated how four agencies from DOD, the Intelligence Community, Department of Homeland Security (DHS), and Department of Transportation (DOT) could share Automatic Identification System (AIS) data in a common format using shared enterprise service components.

PDS4 - Some Principles for Agile Data Curation

NASA Astrophysics Data System (ADS)

Hughes, J. S.; Crichton, D. J.; Hardman, S. H.; Joyner, R.; Algermissen, S.; Padams, J.

2015-12-01

PDS4, a research data management and curation system for NASA's Planetary Science Archive, was developed using principles that promote the characteristics of agile development. The result is an efficient system that produces better research data products while using less resources (time, effort, and money) and maximizes their usefulness for current and future scientists. The key principle is architectural. The PDS4 information architecture is developed and maintained independent of the infrastructure's process, application and technology architectures. The information architecture is based on an ontology-based information model developed to leverage best practices from standard reference models for digital archives, digital object registries, and metadata registries and capture domain knowledge from a panel of planetary science domain experts. The information model provides a sharable, stable, and formal set of information requirements for the system and is the primary source for information to configure most system components, including the product registry, search engine, validation and display tools, and production pipelines. Multi-level governance is also allowed for the effective management of the informational elements at the common, discipline, and project level. This presentation will describe the development principles, components, and uses of the information model and how an information model-driven architecture exhibits characteristics of agile curation including early delivery, evolutionary development, adaptive planning, continuous improvement, and rapid and flexible response to change.

High performance cellular level agent-based simulation with FLAME for the GPU.

PubMed

Richmond, Paul; Walker, Dawn; Coakley, Simon; Romano, Daniela

2010-05-01

Driven by the availability of experimental data and ability to simulate a biological scale which is of immediate interest, the cellular scale is fast emerging as an ideal candidate for middle-out modelling. As with 'bottom-up' simulation approaches, cellular level simulations demand a high degree of computational power, which in large-scale simulations can only be achieved through parallel computing. The flexible large-scale agent modelling environment (FLAME) is a template driven framework for agent-based modelling (ABM) on parallel architectures ideally suited to the simulation of cellular systems. It is available for both high performance computing clusters (www.flame.ac.uk) and GPU hardware (www.flamegpu.com) and uses a formal specification technique that acts as a universal modelling format. This not only creates an abstraction from the underlying hardware architectures, but avoids the steep learning curve associated with programming them. In benchmarking tests and simulations of advanced cellular systems, FLAME GPU has reported massive improvement in performance over more traditional ABM frameworks. This allows the time spent in the development and testing stages of modelling to be drastically reduced and creates the possibility of real-time visualisation for simple visual face-validation.

Coordination control of flexible manufacturing systems

NASA Astrophysics Data System (ADS)

Menon, Satheesh R.

One of the first attempts was made to develop a model driven system for coordination control of Flexible Manufacturing Systems (FMS). The structure and activities of the FMS are modeled using a colored Petri Net based system. This approach has the advantage of being able to model the concurrency inherent in the system. It provides a method for encoding the system state, state transitions and the feasible transitions at any given state. Further structural analysis (for detecting conflicting actions, deadlocks which might occur during operation, etc.) can be performed. The problem is also addressed of implementing and testing the behavior of existing dynamic scheduling approaches in simulations of realistic situations. A simulation architecture was proposed and performance evaluation was carried out for establishing the correctness of the model, stability of the system from a structural (deadlocks) and temporal (boundedness of backlogs) points of view, and for collection of statistics for performance measures such as machine and robot utilizations, average wait times and idle times of resources. A real-time implementation architecture for the coordination controller was also developed and implemented in a software simulated environment. Given the current technology of FMS control, the model-driven colored Petri net-based approach promises to develop a very flexible control environment.

Non-destructive determination of Malondialdehyde (MDA) distribution in oilseed rape leaves by laboratory scale NIR hyperspectral imaging

NASA Astrophysics Data System (ADS)

Kong, Wenwen; Liu, Fei; Zhang, Chu; Zhang, Jianfeng; Feng, Hailin

2016-10-01

The feasibility of hyperspectral imaging with 400-1000 nm was investigated to detect malondialdehyde (MDA) content in oilseed rape leaves under herbicide stress. After comparing the performance of different preprocessing methods, linear and nonlinear calibration models, the optimal prediction performance was achieved by extreme learning machine (ELM) model with only 23 wavelengths selected by competitive adaptive reweighted sampling (CARS), and the result was RP = 0.929 and RMSEP = 2.951. Furthermore, MDA distribution map was successfully achieved by partial least squares (PLS) model with CARS. This study indicated that hyperspectral imaging technology provided a fast and nondestructive solution for MDA content detection in plant leaves.

MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA

PubMed Central

Berke, Ian C; Modis, Yorgo

2012-01-01

Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood. Here, we show that MDA5 cooperatively binds short RNA ligands as a dimer with a 16–18-basepair footprint. A crystal structure of the MDA5 helicase-insert domain demonstrates an evolutionary relationship with the archaeal Hef helicases. In X-ray solution structures, the CARDs in unliganded MDA5 are flexible, and RNA binds on one side of an asymmetric MDA5 dimer, bridging the two subunits. On longer RNA, full-length and CARD-deleted MDA5 constructs assemble into ATP-sensitive filaments. We propose a signalling model in which the CARDs on MDA5–RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry. PMID:22314235

MDA5 assembles into a polar helical filament on dsRNA

PubMed Central

Berke, Ian C.; Yu, Xiong; Modis, Yorgo; Egelman, Edward H.

2012-01-01

Melanoma differentiation-associated protein 5 (MDA5) detects viral dsRNA in the cytoplasm. On binding of RNA, MDA5 forms polymers, which trigger assembly of the signaling adaptor mitochondrial antiviral-signaling protein (MAVS) into its active fibril form. The molecular mechanism of MDA5 signaling is not well understood, however. Here we show that MDA5 forms helical filaments on dsRNA and report the 3D structure of the filaments using electron microscopy (EM) and image reconstruction. MDA5 assembles into a polar, single-start helix around the RNA. Fitting of an MDA5 homology model into the structure suggests a key role for the MDA5 C-terminal domain in cooperative filament assembly. Our study supports a signal transduction mechanism in which the helical array of MDA5 within filaments nucleates the assembly of MAVS fibrils. We conclude that MDA5 is a polymerization-dependent signaling platform that uses the amyloid-like self-propagating properties of MAVS to amplify signaling. PMID:23090998

Empowering citizens with access control mechanisms to their personal health resources.

PubMed

Calvillo, J; Román, I; Roa, L M

2013-01-01

Advancements in information and communication technologies have allowed the development of new approaches to the management and use of healthcare resources. Nowadays it is possible to address complex issues such as meaningful access to distributed data or communication and understanding among heterogeneous systems. As a consequence, the discussion focuses on the administration of the whole set of resources providing knowledge about a single subject of care (SoC). New trends make the SoC administrator and responsible for all these elements (related to his/her demographic data, health, well-being, social conditions, etc.) and s/he is granted the ability of controlling access to them by third parties. The subject of care exchanges his/her passive role without any decision capacity for an active one allowing to control who accesses what. We study the necessary access control infrastructure to support this approach and develop mechanisms based on semantic tools to assist the subject of care with the specification of access control policies. This infrastructure is a building block of a wider scenario, the Person-Oriented Virtual Organization (POVO), aiming at integrating all the resources related to each citizen's health-related data. The POVO covers the wide range and heterogeneity of available healthcare resources (e.g., information sources, monitoring devices, or software simulation tools) and grants each SoC the access control to them. Several methodological issues are crucial for the design of the targeted infrastructure. The distributed system concept and focus are reviewed from the service oriented architecture (SOA) perspective. The main frameworks for the formalization of distributed system architectures (Reference Model-Open Distributed Processing, RM-ODP; and Model Driven Architecture, MDA) are introduced, as well as how the use of the Unified Modelling Language (UML) is standardized. The specification of access control policies and decision making mechanisms are essential keys for this approach and they are accomplished by using semantic technologies (i.e., ontologies, rule languages, and inference engines). The results are mainly focused on the security and access control of the proposed scenario. An ontology has been designed and developed for the POVO covering the terminology of the scenario and easing the automation of administration tasks. Over that ontology, an access control mechanism based on rule languages allows specifying access control policies, and an inference engine performs the decision making process automatically. The usability of solutions to ease administration tasks to the SoC is improved by the Me-As-An-Admin (M3A) application. This guides the SoC through the specification of personal access control policies to his/her distributed resources by using semantic technologies (e.g., metamodeling, model-to-text transformations, etc.). All results are developed as services and included in an architecture in accordance with standards and principles of openness and interoperability. Current technology can bring health, social and well-being care actually centered on citizens, and granting each person the management of his/her health information. However, the application of technology without adopting methodologies or normalized guidelines will reduce the interoperability of solutions developed, failing in the development of advanced services and improved scenarios for health delivery. Standards and reference architectures can be cornerstones for future-proof and powerful developments. Finally, not only technology must follow citizen-centric approaches, but also the gaps needing legislative efforts that support these new paradigms of healthcare delivery must be identified and addressed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A generic architecture for an adaptive, interoperable and intelligent type 2 diabetes mellitus care system.

PubMed

Uribe, Gustavo A; Blobel, Bernd; López, Diego M; Schulz, Stefan

2015-01-01

Chronic diseases such as Type 2 Diabetes Mellitus (T2DM) constitute a big burden to the global health economy. T2DM Care Management requires a multi-disciplinary and multi-organizational approach. Because of different languages and terminologies, education, experiences, skills, etc., such an approach establishes a special interoperability challenge. The solution is a flexible, scalable, business-controlled, adaptive, knowledge-based, intelligent system following a systems-oriented, architecture-centric, ontology-based and policy-driven approach. The architecture of real systems is described, using the basics and principles of the Generic Component Model (GCM). For representing the functional aspects of a system the Business Process Modeling Notation (BPMN) is used. The system architecture obtained is presented using a GCM graphical notation, class diagrams and BPMN diagrams. The architecture-centric approach considers the compositional nature of the real world system and its functionalities, guarantees coherence, and provides right inferences. The level of generality provided in this paper facilitates use case specific adaptations of the system. By that way, intelligent, adaptive and interoperable T2DM care systems can be derived from the presented model as presented in another publication.

Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations.

PubMed

Gädt, Torben; Ieong, Nga Sze; Cambridge, Graeme; Winnik, Mitchell A; Manners, Ian

2009-02-01

Block copolymers consist of two or more chemically distinct polymer segments, or blocks, connected by a covalent link. In a selective solvent for one of the blocks, core-corona micelle structures are formed. We demonstrate that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers. The use of platelet micelles as initiators enables the formation of scarf-like architectures in which cylindrical micelle tassels of controlled length are grown from specific crystal faces. A similar process enables the fabrication of brushes of cylindrical micelles on a crystalline homopolymer substrate. Living polymerizations driven by heteroepitaxial growth can also be accomplished and are illustrated by the formation of tri- and pentablock and scarf architectures with cylinder-cylinder and platelet-cylinder connections, respectively, that involve different core-forming metalloblocks.

Non-destructive determination of Malondialdehyde (MDA) distribution in oilseed rape leaves by laboratory scale NIR hyperspectral imaging

PubMed Central

Kong, Wenwen; Liu, Fei; Zhang, Chu; Zhang, Jianfeng; Feng, Hailin

2016-01-01

The feasibility of hyperspectral imaging with 400–1000 nm was investigated to detect malondialdehyde (MDA) content in oilseed rape leaves under herbicide stress. After comparing the performance of different preprocessing methods, linear and nonlinear calibration models, the optimal prediction performance was achieved by extreme learning machine (ELM) model with only 23 wavelengths selected by competitive adaptive reweighted sampling (CARS), and the result was RP = 0.929 and RMSEP = 2.951. Furthermore, MDA distribution map was successfully achieved by partial least squares (PLS) model with CARS. This study indicated that hyperspectral imaging technology provided a fast and nondestructive solution for MDA content detection in plant leaves. PMID:27739491

Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a 1H-NMR-based untargeted metabolomics approach.

PubMed

Almanza-Aguilera, Enrique; Urpi-Sarda, Mireia; Llorach, Rafael; Vázquez-Fresno, Rosa; Garcia-Aloy, Mar; Carmona, Francesc; Sanchez, Alex; Madrid-Gambin, Francisco; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina

2017-10-01

The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A 1 H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

A Distributed Laboratory for Event-Driven Coastal Prediction and Hazard Planning

NASA Astrophysics Data System (ADS)

Bogden, P.; Allen, G.; MacLaren, J.; Creager, G. J.; Flournoy, L.; Sheng, Y. P.; Graber, H.; Graves, S.; Conover, H.; Luettich, R.; Perrie, W.; Ramakrishnan, L.; Reed, D. A.; Wang, H. V.

2006-12-01

The 2005 Atlantic hurricane season was the most active in recorded history. Collectively, 2005 hurricanes caused more than 2,280 deaths and record damages of over 100 billion dollars. Of the storms that made landfall, Dennis, Emily, Katrina, Rita, and Wilma caused most of the destruction. Accurate predictions of storm-driven surge, wave height, and inundation can save lives and help keep recovery costs down, provided the information gets to emergency response managers in time. The information must be available well in advance of landfall so that responders can weigh the costs of unnecessary evacuation against the costs of inadequate preparation. The SURA Coastal Ocean Observing and Prediction (SCOOP) Program is a multi-institution collaboration implementing a modular, distributed service-oriented architecture for real time prediction and visualization of the impacts of extreme atmospheric events. The modular infrastructure enables real-time prediction of multi- scale, multi-model, dynamic, data-driven applications. SURA institutions are working together to create a virtual and distributed laboratory integrating coastal models, simulation data, and observations with computational resources and high speed networks. The loosely coupled architecture allows teams of computer and coastal scientists at multiple institutions to innovate complex system components that are interconnected with relatively stable interfaces. The operational system standardizes at the interface level to enable substantial innovation by complementary communities of coastal and computer scientists. This architectural philosophy solves a long-standing problem associated with the transition from research to operations. The SCOOP Program thereby implements a prototype laboratory consistent with the vision of a national, multi-agency initiative called the Integrated Ocean Observing System (IOOS). Several service- oriented components of the SCOOP enterprise architecture have already been designed and implemented, including data archive and transport services, metadata registry and retrieval (catalog), resource management, and portal interfaces. SCOOP partners are integrating these at the service level and implementing reconfigurable workflows for several kinds of user scenarios, and are working with resource providers to prototype new policies and technologies for on-demand computing.

MoSeS: Modelling and Simulation for e-Social Science.

PubMed

Townend, Paul; Xu, Jie; Birkin, Mark; Turner, Andy; Wu, Belinda

2009-07-13

MoSeS (Modelling and Simulation for e-Social Science) is a research node of the National Centre for e-Social Science. MoSeS uses e-Science techniques to execute an events-driven model that simulates discrete demographic processes; this allows us to project the UK population 25 years into the future. This paper describes the architecture, simulation methodology and latest results obtained by MoSeS.

Intelligent fuzzy controller for event-driven real time systems

NASA Technical Reports Server (NTRS)

Grantner, Janos; Patyra, Marek; Stachowicz, Marian S.

1992-01-01

Most of the known linguistic models are essentially static, that is, time is not a parameter in describing the behavior of the object's model. In this paper we show a model for synchronous finite state machines based on fuzzy logic. Such finite state machines can be used to build both event-driven, time-varying, rule-based systems and the control unit section of a fuzzy logic computer. The architecture of a pipelined intelligent fuzzy controller is presented, and the linguistic model is represented by an overall fuzzy relation stored in a single rule memory. A VLSI integrated circuit implementation of the fuzzy controller is suggested. At a clock rate of 30 MHz, the controller can perform 3 MFLIPS on multi-dimensional fuzzy data.

Teleport Generation 3 (Teleport Gen 3)

DTIC Science & Technology

2016-03-01

Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA - Information...144A) reported since the previous MAIS Annual Report to Congress. The program recently achieved a FDD from the MDA on February 13, 2015. Teleport Gen 3...February 13, 2015 granting approval of the FDD . Acronyms and Abbreviations MLGC - MUOS to Legacy UHF SATCOM Gateway Component MOT&E - Multiservice

MODULAR APPLICATION OF COMPUTATIONAL MODELS OF INHALED REACTIVE GAS DOSIMETRY FOR RISK ASSESSMENT OF RESPIRATORY TRACT TOXICITY: CHLORINE

EPA Science Inventory

Inhaled reactive gases typically cause respiratory tract toxicity with a prominent proximal to distal lesion pattern. This pattern is largely driven by airflow and interspecies differences between rodents and humans result from factors such as airway architecture, ventilation ra...

The Role of Multiphysics Simulation in Multidisciplinary Analysis

NASA Technical Reports Server (NTRS)

Rifai, Steven M.; Ferencz, Robert M.; Wang, Wen-Ping; Spyropoulos, Evangelos T.; Lawrence, Charles; Melis, Matthew E.

1998-01-01

This article describes the applications of the Spectrum(Tm) Solver in Multidisciplinary Analysis (MDA). Spectrum, a multiphysics simulation software based on the finite element method, addresses compressible and incompressible fluid flow, structural, and thermal modeling as well as the interaction between these disciplines. Multiphysics simulation is based on a single computational framework for the modeling of multiple interacting physical phenomena. Interaction constraints are enforced in a fully-coupled manner using the augmented-Lagrangian method. Within the multiphysics framework, the finite element treatment of fluids is based on Galerkin-Least-Squares (GLS) method with discontinuity capturing operators. The arbitrary-Lagrangian-Eulerian method is utilized to account for deformable fluid domains. The finite element treatment of solids and structures is based on the Hu-Washizu variational principle. The multiphysics architecture lends itself naturally to high-performance parallel computing. Aeroelastic, propulsion, thermal management and manufacturing applications are presented.

An MDA Based Ontology Platform: AIR

NASA Astrophysics Data System (ADS)

Gaševic, Dragan; Djuric, Dragan; Devedžic, Vladan

In the past few years, software engineering has witnessed two major shifts: model-driven engineering has entered the mainstream, and some leading development tools have become open and extensible.1 AI has always been a spring of new ideas that have been adopted in software engineering, but most of its gems have stayed buried in laboratories, available only to a limited number of AI practitioners. Should AI tools be integrated into mainstream tools and could it be done? We think that it is feasible, and that both communities can benefit from this integration. In fact, some efforts in this direction have already been made, both by major industrial standardization bodies such as the OMG, and by academic laboratories.

Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

PubMed Central

Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

2012-01-01

Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

Modular design, application architecture, and usage of a self-service model for enterprise data delivery: The Duke Enterprise Data Unified Content Explorer (DEDUCE)

PubMed Central

Horvath, Monica M.; Rusincovitch, Shelley A.; Brinson, Stephanie; Shang, Howard C.; Evans, Steve; Ferranti, Jeffrey M.

2015-01-01

Purpose Data generated in the care of patients are widely used to support clinical research and quality improvement, which has hastened the development of self-service query tools. User interface design for such tools, execution of query activity, and underlying application architecture have not been widely reported, and existing tools reflect a wide heterogeneity of methods and technical frameworks. We describe the design, application architecture, and use of a self-service model for enterprise data delivery within Duke Medicine. Methods Our query platform, the Duke Enterprise Data Unified Content Explorer (DEDUCE), supports enhanced data exploration, cohort identification, and data extraction from our enterprise data warehouse (EDW) using a series of modular environments that interact with a central keystone module, Cohort Manager (CM). A data-driven application architecture is implemented through three components: an application data dictionary, the concept of “smart dimensions”, and dynamically-generated user interfaces. Results DEDUCE CM allows flexible hierarchies of EDW queries within a grid-like workspace. A cohort “join” functionality allows switching between filters based on criteria occurring within or across patient encounters. To date, 674 users have been trained and activated in DEDUCE, and logon activity shows a steady increase, with variability between months. A comparison of filter conditions and export criteria shows that these activities have different patterns of usage across subject areas. Conclusions Organizations with sophisticated EDWs may find that users benefit from development of advanced query functionality, complimentary to the user interfaces and infrastructure used in other well-published models. Driven by its EDW context, the DEDUCE application architecture was also designed to be responsive to source data and to allow modification through alterations in metadata rather than programming, allowing an agile response to source system changes. PMID:25051403

Modular design, application architecture, and usage of a self-service model for enterprise data delivery: the Duke Enterprise Data Unified Content Explorer (DEDUCE).

PubMed

Horvath, Monica M; Rusincovitch, Shelley A; Brinson, Stephanie; Shang, Howard C; Evans, Steve; Ferranti, Jeffrey M

2014-12-01

Data generated in the care of patients are widely used to support clinical research and quality improvement, which has hastened the development of self-service query tools. User interface design for such tools, execution of query activity, and underlying application architecture have not been widely reported, and existing tools reflect a wide heterogeneity of methods and technical frameworks. We describe the design, application architecture, and use of a self-service model for enterprise data delivery within Duke Medicine. Our query platform, the Duke Enterprise Data Unified Content Explorer (DEDUCE), supports enhanced data exploration, cohort identification, and data extraction from our enterprise data warehouse (EDW) using a series of modular environments that interact with a central keystone module, Cohort Manager (CM). A data-driven application architecture is implemented through three components: an application data dictionary, the concept of "smart dimensions", and dynamically-generated user interfaces. DEDUCE CM allows flexible hierarchies of EDW queries within a grid-like workspace. A cohort "join" functionality allows switching between filters based on criteria occurring within or across patient encounters. To date, 674 users have been trained and activated in DEDUCE, and logon activity shows a steady increase, with variability between months. A comparison of filter conditions and export criteria shows that these activities have different patterns of usage across subject areas. Organizations with sophisticated EDWs may find that users benefit from development of advanced query functionality, complimentary to the user interfaces and infrastructure used in other well-published models. Driven by its EDW context, the DEDUCE application architecture was also designed to be responsive to source data and to allow modification through alterations in metadata rather than programming, allowing an agile response to source system changes. Copyright © 2014 Elsevier Inc. All rights reserved.

The Best of all Possible Worlds: Applying the Model Driven Architecture Approach to a JC3IEDM OWL Ontology Modeled in UML

DTIC Science & Technology

2014-04-25

EA’s Java application programming interface (API), the team built a tool called OWL2EA that can ingest an OWL file and generate the corresponding UML...ObjectItemStructure specification shown in Figure 10. Running this script in the relational database server MySQL creates the physical schema that

Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

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

Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com; Rojas, Paola, E-mail: parojas2010@gmail.com; Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2more » and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.« less

Managing Complex Interoperability Solutions using Model-Driven Architecture

DTIC Science & Technology

2011-06-01

such as Oracle or MySQL . Each data model for a specific RDBMS is a distinct PSM. Or the system may want to exchange information with other C2...reduced number of transformations, e.g., from an RDBMS physical schema to the corresponding SQL script needed to instantiate the tables in a relational...tance of models. In engineering, a model serves several purposes: 1. It presents an abstract view of a complex system or of a complex information

Reference Architecture Model Enabling Standards Interoperability.

PubMed

Blobel, Bernd

2017-01-01

Advanced health and social services paradigms are supported by a comprehensive set of domains managed by different scientific disciplines. Interoperability has to evolve beyond information and communication technology (ICT) concerns, including the real world business domains and their processes, but also the individual context of all actors involved. So, the system must properly reflect the environment in front and around the computer as essential and even defining part of the health system. This paper introduces an ICT-independent system-theoretical, ontology-driven reference architecture model allowing the representation and harmonization of all domains involved including the transformation into an appropriate ICT design and implementation. The entire process is completely formalized and can therefore be fully automated.

Framework for a clinical information system.

PubMed

Van de Velde, R

2000-01-01

The current status of our work towards the design and implementation of a reference architecture for a Clinical Information System is presented. This architecture has been developed and implemented based on components following a strong underlying conceptual and technological model. Common Object Request Broker and n-tier technology featuring centralised and departmental clinical information systems as the back-end store for all clinical data are used. Servers located in the 'middle' tier apply the clinical (business) model and application rules to communicate with so-called 'thin client' workstations. The main characteristics are the focus on modelling and reuse of both data and business logic as there is a shift away from data and functional modelling towards object modelling. Scalability as well as adaptability to constantly changing requirements via component driven computing are the main reasons for that approach.

MDA-9/syntenin and IGFBP-2 promote angiogenesis in human melanoma.

PubMed

Das, Swadesh K; Bhutia, Sujit K; Azab, Belal; Kegelman, Timothy P; Peachy, Leyla; Santhekadur, Prasanna K; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2013-01-15

Melanoma differentiation-associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacologic approaches were used to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma, and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, chorioallantoic membrane (CAM) assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several proangiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the extracellular matrix (ECM), activating Src and FAK resulting in activation by phosphorylation of Akt, which induces hypoxia inducible factor 1-α (HIF-1α). The HIF-1α activates transcription of insulin growth factor-binding protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell nonautonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (nonautonomous).

MDA-9/Syntenin and IGFBP-2 Promote Angiogenesis in Human Melanoma

PubMed Central

Das, Swadesh K.; Bhutia, Sujit K.; Azab, Belal; Kegelman, Timothy P.; Peachy, Leyla; Santhekadur, Prasanna K.; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B.

2012-01-01

Melanoma differentiation associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacological approaches were employed to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, CAM assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several pro-angiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the ECM activating Src and FAK resulting in activation by phosphorylation of Akt, which induces HIF-1α. The HIF-1α activates transcription of Insulin Growth Factor Binding Protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell non-autonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (non-autonomous). PMID:23233738

The need of adequate information to achieve total compliance of mass drug administration in Pekalongan

NASA Astrophysics Data System (ADS)

Ginandjar, Praba; Saraswati, Lintang Dian; Taufik, Opik; Nurjazuli; Widjanarko, Bagoes

2017-02-01

World Health Organization (WHO) initiated The Global Program to Eliminate Lymphatic Filariasis (LF) through mass drug administration (MDA). Pekalongan started MDA in 2011. Yet the LF prevalence in 2015 remained exceed the threshold (1%). This study aimed to describe the inhibiting factors related to the compliance of MDA in community level. This was a rapid survey with cross sectional approach. A two-stages random sampling was used in this study. In the first stage, 25 clusters were randomly selected from 27 villages with proportionate to population size (PPS) methods (C-Survey). In the second stage, 10 subjects were randomly selected from each cluster. Subject consisted of 250 respondents from 25 selected clusters. Variables consisted of MDA coverage, practice of taking medication during MDA, enabling and inhibiting factors to MDA in community level. The results showed most respondents had poor knowledge on filariasis, which influence awareness of the disease. Health-illness perception, did not receive the drugs, lactation, side effect, and size of the drugs were dominant factors of non-compliance to MDA. MDA information and community empowerment were needed to improve MDA coverage. Further study to explore the appropriate model of socialization will support the success of MDA program

Strategic Industrial Alliances in Paper Industry: XML- vs Ontology-Based Integration Platforms

ERIC Educational Resources Information Center

Naumenko, Anton; Nikitin, Sergiy; Terziyan, Vagan; Zharko, Andriy

2005-01-01

Purpose: To identify cases related to design of ICT platforms for industrial alliances, where the use of Ontology-driven architectures based on Semantic web standards is more advantageous than application of conventional modeling together with XML standards. Design/methodology/approach: A comparative analysis of the two latest and the most obvious…

Semantic interoperability--HL7 Version 3 compared to advanced architecture standards.

PubMed

Blobel, B G M E; Engel, K; Pharow, P

2006-01-01

To meet the challenge for high quality and efficient care, highly specialized and distributed healthcare establishments have to communicate and co-operate in a semantically interoperable way. Information and communication technology must be open, flexible, scalable, knowledge-based and service-oriented as well as secure and safe. For enabling semantic interoperability, a unified process for defining and implementing the architecture, i.e. structure and functions of the cooperating systems' components, as well as the approach for knowledge representation, i.e. the used information and its interpretation, algorithms, etc. have to be defined in a harmonized way. Deploying the Generic Component Model, systems and their components, underlying concepts and applied constraints must be formally modeled, strictly separating platform-independent from platform-specific models. As HL7 Version 3 claims to represent the most successful standard for semantic interoperability, HL7 has been analyzed regarding the requirements for model-driven, service-oriented design of semantic interoperable information systems, thereby moving from a communication to an architecture paradigm. The approach is compared with advanced architectural approaches for information systems such as OMG's CORBA 3 or EHR systems such as GEHR/openEHR and CEN EN 13606 Electronic Health Record Communication. HL7 Version 3 is maturing towards an architectural approach for semantic interoperability. Despite current differences, there is a close collaboration between the teams involved guaranteeing a convergence between competing approaches.

The Action Execution Process Implemented in Different Cognitive Architectures: A Review

NASA Astrophysics Data System (ADS)

Dong, Daqi; Franklin, Stan

2014-12-01

An agent achieves its goals by interacting with its environment, cyclically choosing and executing suitable actions. An action execution process is a reasonable and critical part of an entire cognitive architecture, because the process of generating executable motor commands is not only driven by low-level environmental information, but is also initiated and affected by the agent's high-level mental processes. This review focuses on cognitive models of action, or more specifically, of the action execution process, as implemented in a set of popular cognitive architectures. We examine the representations and procedures inside the action execution process, as well as the cooperation between action execution and other high-level cognitive modules. We finally conclude with some general observations regarding the nature of action execution.

A stochastic model for the probability of malaria extinction by mass drug administration.

PubMed

Pemberton-Ross, Peter; Chitnis, Nakul; Pothin, Emilie; Smith, Thomas A

2017-09-18

Mass drug administration (MDA) has been proposed as an intervention to achieve local extinction of malaria. Although its effect on the reproduction number is short lived, extinction may subsequently occur in a small population due to stochastic fluctuations. This paper examines how the probability of stochastic extinction depends on population size, MDA coverage and the reproduction number under control, R c . A simple compartmental model is developed which is used to compute the probability of extinction using probability generating functions. The expected time to extinction in small populations after MDA for various scenarios in this model is calculated analytically. The results indicate that mass drug administration (Firstly, R c must be sustained at R c  < 1.2 to avoid the rapid re-establishment of infections in the population. Secondly, the MDA must produce effective cure rates of >95% to have a non-negligible probability of successful elimination. Stochastic fluctuations only significantly affect the probability of extinction in populations of about 1000 individuals or less. The expected time to extinction via stochastic fluctuation is less than 10 years only in populations less than about 150 individuals. Clustering of secondary infections and of MDA distribution both contribute positively to the potential probability of success, indicating that MDA would most effectively be administered at the household level. There are very limited circumstances in which MDA will lead to local malaria elimination with a substantial probability.

Virtual Plants Need Water Too: Functional-Structural Root System Models in the Context of Drought Tolerance Breeding

PubMed Central

Ndour, Adama; Vadez, Vincent; Pradal, Christophe; Lucas, Mikaël

2017-01-01

Developing a sustainable agricultural model is one of the great challenges of the coming years. The agricultural practices inherited from the Green Revolution of the 1960s show their limits today, and new paradigms need to be explored to counter rising issues such as the multiplication of climate-change related drought episodes. Two such new paradigms are the use of functional-structural plant models to complement and rationalize breeding approaches and a renewed focus on root systems as untapped sources of plant amelioration. Since the late 1980s, numerous functional and structural models of root systems were developed and used to investigate the properties of root systems in soil or lab-conditions. In this review, we focus on the conception and use of such root models in the broader context of research on root-driven drought tolerance, on the basis of root system architecture (RSA) phenotyping. Such models result from the integration of architectural, physiological and environmental data. Here, we consider the different phenotyping techniques allowing for root architectural and physiological study and their limits. We discuss how QTL and breeding studies support the manipulation of RSA as a way to improve drought resistance. We then go over the integration of the generated data within architectural models, how those architectural models can be coupled with functional hydraulic models, and how functional parameters can be measured to feed those models. We then consider the assessment and validation of those hydraulic models through confrontation of simulations to experimentations. Finally, we discuss the up and coming challenges facing root systems functional-structural modeling approaches in the context of breeding. PMID:29018456

Virtual Plants Need Water Too: Functional-Structural Root System Models in the Context of Drought Tolerance Breeding.

PubMed

Ndour, Adama; Vadez, Vincent; Pradal, Christophe; Lucas, Mikaël

2017-01-01

Developing a sustainable agricultural model is one of the great challenges of the coming years. The agricultural practices inherited from the Green Revolution of the 1960s show their limits today, and new paradigms need to be explored to counter rising issues such as the multiplication of climate-change related drought episodes. Two such new paradigms are the use of functional-structural plant models to complement and rationalize breeding approaches and a renewed focus on root systems as untapped sources of plant amelioration. Since the late 1980s, numerous functional and structural models of root systems were developed and used to investigate the properties of root systems in soil or lab-conditions. In this review, we focus on the conception and use of such root models in the broader context of research on root-driven drought tolerance, on the basis of root system architecture (RSA) phenotyping. Such models result from the integration of architectural, physiological and environmental data. Here, we consider the different phenotyping techniques allowing for root architectural and physiological study and their limits. We discuss how QTL and breeding studies support the manipulation of RSA as a way to improve drought resistance. We then go over the integration of the generated data within architectural models, how those architectural models can be coupled with functional hydraulic models, and how functional parameters can be measured to feed those models. We then consider the assessment and validation of those hydraulic models through confrontation of simulations to experimentations. Finally, we discuss the up and coming challenges facing root systems functional-structural modeling approaches in the context of breeding.

Goal-Driven Autonomy and Robust Architecture for Long-Duration Missions (Year 1: 1 July 2013 - 31 July 2014)

DTIC Science & Technology

2014-09-30

Mental Domain = Ω Goal Management goal change goal input World =Ψ Memory Mission & Goals( ) World Model (-Ψ) Episodic Memory Semantic Memory ...Activations Trace Meta-Level Control Introspective Monitoring Memory Reasoning Trace ( ) Strategies Episodic Memory Metaknowledge Self Model...it is from incorrect or missing memory associations (i.e., indices). Similarly, correct information may exist in the input stream, but may not be

The Best of All Possible Worlds: Applying the Model Driven Architecture Approach to a JC3IEDM OWL Ontology Modeled in UML

DTIC Science & Technology

2014-06-01

from the ODM standard. Leveraging SPARX EA’s Java application programming interface (API), the team built a tool called OWL2EA that can ingest an OWL...server MySQL creates the physical schema that enables a user to store and retrieve data conforming to the vocabulary of the JC3IEDM. 6. GENERATING AN

Software Product Lines: Report of the 2009 U.S. Army Software Product Line Workshop

DTIC Science & Technology

2009-04-01

record system was fielded in 2008. One early challenge for Overwatch was coming up with a funding model that would support core asset development (a...match the organizational model to the funding model . Product line architecture is essential. Address product line requirements up front. Put processes...when trying to move from a customer-driven, product-specific funding model to one in which at least some of the funds are allocated to the creation and

Variation of the hydraulic properties within gravity-driven deposits in basinal carbonates

NASA Astrophysics Data System (ADS)

Jablonska, D.; Zambrano, M.; Emanuele, T.; Di Celma, C.

2017-12-01

Deepwater gravity-driven deposits represent important stratigraphic heterogeneities within basinal sedimentary successions. A poor understanding of their distribution, internal architecture (at meso- and micro-scale) and hydraulic properties (porosity and permeability), may lead to unexpected compartmentalization issues in reservoir analysis. In this study, we examine gravity-driven deposits within the basinal-carbonate Maiolica Formation adjacent to the Apulian Carbonate Plaftorm, southern Italy. Maiolica formation is represented by horizontal layers of thin-bedded cherty pelagic limestones often intercalated by mass-transport deposits (slumps, debris-flow deposits) and calcarenites of diverse thickness (0.1 m - 40 m) and lateral extent (100 m - >500 m). Locally, gravity-driven deposits compose up to 60 % of the exposed succession. These deposits display broad array of internal architectures (from faulted and folded strata to conglomerates) and various texture. In order to further constrain the variation of the internal architectures and fracture distribution within gravity-driven deposits, field sedimentological and structural analyses were performed. To examine the texture and hydraulic properties of various lithofacies, the laboratory porosity measurements of suitable rock samples were undertaken. These data were supported by 3D pore network quantitative analysis of X-ray Computed microtomography (MicroCT) images performed at resolutions 1.25 and 2.0 microns. This analysis helped to describe the pores and grains geometrical and morphological properties (such as size, shape, specific surface area) and the hydraulic properties (porosity and permeability) of various lithofacies. The integration of the analyses allowed us to show how the internal architecture and the hydraulic properties vary in different types of gravity-driven deposits within the basinal carbonate succession.

An Object Oriented Extensible Architecture for Affordable Aerospace Propulsion Systems

NASA Technical Reports Server (NTRS)

Follen, Gregory J.; Lytle, John K. (Technical Monitor)

2002-01-01

Driven by a need to explore and develop propulsion systems that exceeded current computing capabilities, NASA Glenn embarked on a novel strategy leading to the development of an architecture that enables propulsion simulations never thought possible before. Full engine 3 Dimensional Computational Fluid Dynamic propulsion system simulations were deemed impossible due to the impracticality of the hardware and software computing systems required. However, with a software paradigm shift and an embracing of parallel and distributed processing, an architecture was designed to meet the needs of future propulsion system modeling. The author suggests that the architecture designed at the NASA Glenn Research Center for propulsion system modeling has potential for impacting the direction of development of affordable weapons systems currently under consideration by the Applied Vehicle Technology Panel (AVT). This paper discusses the salient features of the NPSS Architecture including its interface layer, object layer, implementation for accessing legacy codes, numerical zooming infrastructure and its computing layer. The computing layer focuses on the use and deployment of these propulsion simulations on parallel and distributed computing platforms which has been the focus of NASA Ames. Additional features of the object oriented architecture that support MultiDisciplinary (MD) Coupling, computer aided design (CAD) access and MD coupling objects will be discussed. Included will be a discussion of the successes, challenges and benefits of implementing this architecture.

MBSE-Driven Visualization of Requirements Allocation and Traceability

NASA Technical Reports Server (NTRS)

Jackson, Maddalena; Wilkerson, Marcus

2016-01-01

In a Model Based Systems Engineering (MBSE) infusion effort, there is a usually a concerted effort to define the information architecture, ontologies, and patterns that drive the construction and architecture of MBSE models, but less attention is given to the logical follow-on of that effort: how to practically leverage the resulting semantic richness of a well-formed populated model to enable systems engineers to work more effectively, as MBSE promises. While ontologies and patterns are absolutely necessary, an MBSE effort must also design and provide practical demonstration of value (through human-understandable representations of model data that address stakeholder concerns) or it will not succeed. This paper will discuss opportunities that exist for visualization in making the richness of a well-formed model accessible to stakeholders, specifically stakeholders who rely on the model for their day-to-day work. This paper will discuss the value added by MBSE-driven visualizations in the context of a small case study of interactive visualizations created and used on NASA's proposed Europa Mission. The case study visualizations were created for the purpose of understanding and exploring targeted aspects of requirements flow, allocation, and comparing the structure of that flow-down to a conceptual project decomposition. The work presented in this paper is an example of a product that leverages the richness and formalisms of our knowledge representation while also responding to the quality attributes SEs care about.

An Emotion Aware Task Automation Architecture Based on Semantic Technologies for Smart Offices

PubMed Central

2018-01-01

The evolution of the Internet of Things leads to new opportunities for the contemporary notion of smart offices, where employees can benefit from automation to maximize their productivity and performance. However, although extensive research has been dedicated to analyze the impact of workers’ emotions on their job performance, there is still a lack of pervasive environments that take into account emotional behaviour. In addition, integrating new components in smart environments is not straightforward. To face these challenges, this article proposes an architecture for emotion aware automation platforms based on semantic event-driven rules to automate the adaptation of the workplace to the employee’s needs. The main contributions of this paper are: (i) the design of an emotion aware automation platform architecture for smart offices; (ii) the semantic modelling of the system; and (iii) the implementation and evaluation of the proposed architecture in a real scenario. PMID:29748468

An Emotion Aware Task Automation Architecture Based on Semantic Technologies for Smart Offices.

PubMed

Muñoz, Sergio; Araque, Oscar; Sánchez-Rada, J Fernando; Iglesias, Carlos A

2018-05-10

The evolution of the Internet of Things leads to new opportunities for the contemporary notion of smart offices, where employees can benefit from automation to maximize their productivity and performance. However, although extensive research has been dedicated to analyze the impact of workers’ emotions on their job performance, there is still a lack of pervasive environments that take into account emotional behaviour. In addition, integrating new components in smart environments is not straightforward. To face these challenges, this article proposes an architecture for emotion aware automation platforms based on semantic event-driven rules to automate the adaptation of the workplace to the employee’s needs. The main contributions of this paper are: (i) the design of an emotion aware automation platform architecture for smart offices; (ii) the semantic modelling of the system; and (iii) the implementation and evaluation of the proposed architecture in a real scenario.

Architectural approaches for HL7-based health information systems implementation.

PubMed

López, D M; Blobel, B

2010-01-01

Information systems integration is hard, especially when semantic and business process interoperability requirements need to be met. To succeed, a unified methodology, approaching different aspects of systems architecture such as business, information, computational, engineering and technology viewpoints, has to be considered. The paper contributes with an analysis and demonstration on how the HL7 standard set can support health information systems integration. Based on the Health Information Systems Development Framework (HIS-DF), common architectural models for HIS integration are analyzed. The framework is a standard-based, consistent, comprehensive, customizable, scalable methodology that supports the design of semantically interoperable health information systems and components. Three main architectural models for system integration are analyzed: the point to point interface, the messages server and the mediator models. Point to point interface and messages server models are completely supported by traditional HL7 version 2 and version 3 messaging. The HL7 v3 standard specification, combined with service-oriented, model-driven approaches provided by HIS-DF, makes the mediator model possible. The different integration scenarios are illustrated by describing a proof-of-concept implementation of an integrated public health surveillance system based on Enterprise Java Beans technology. Selecting the appropriate integration architecture is a fundamental issue of any software development project. HIS-DF provides a unique methodological approach guiding the development of healthcare integration projects. The mediator model - offered by the HIS-DF and supported in HL7 v3 artifacts - is the more promising one promoting the development of open, reusable, flexible, semantically interoperable, platform-independent, service-oriented and standard-based health information systems.

Spatial clustering and meteorological drivers of summer ozone in Europe

NASA Astrophysics Data System (ADS)

Carro-Calvo, Leopoldo; Ordóñez, Carlos; García-Herrera, Ricardo; Schnell, Jordan L.

2017-04-01

We present a regionalization of summer near-surface ozone (O3) in Europe. For this purpose we apply a K-means algorithm on a gridded MDA8 O3 (maximum daily average 8-h ozone) dataset covering a European domain [15° W - 30° E, 35°-70° N] at 1° x 1° horizontal resolution for the 1998-2012 period. This dataset was compiled by merging observations from the European Monitoring and Evaluation Programme (EMEP) and the European Environment Agency's air quality database (AirBase). The K-means method allows identifying sets of different regions where the O3 concentrations present coherent spatiotemporal patterns and are thus expected to be driven by similar meteorological factors. After some testing, 9 regions were selected: the British Isles, North-Central Europe, Northern Scandinavia, the Baltic countries, the Iberian Peninsula, Western Europe, South-Central Europe, Eastern Europe and the Balkans. For each region we examine the synoptic situations associated with elevated ozone extremes (days exceeding the 95th percentile of the summer MDA8 O3 distribution). Our analyses reveal that there are basically two different kinds of regions in Europe: (a) those in the centre and south of the continent where ozone extremes are associated with elevated temperature within the same region and (b) those in northern Europe where ozone extremes are driven by southerly advection of air masses from warmer, more polluted areas. Even when the observed patterns were initially identified only for days registering high O3 extremes, all summer days can be projected on such patterns to identify the main modes of meteorological variability of O3. We have found that such modes are partly responsible for the day-to-day variability in the O3 concentrations and can explain a relatively large fraction (from 44 to 88 %, depending on the region) of the interannual variability of summer mean MDA8 O3 during the period of analysis. On the other hand, some major teleconnection patterns have been tested but do not seem to exert a large impact on the variability of surface O3 over most regions. The identification of these independent regions where surface ozone presents a coherent behaviour and responds similarly to specific meteorological modes of variability has multiple applications. For instance, the performance of chemical transport models (CTMs) and chemistry-climate models (CCMs) can be separately assessed over such regions to identify areas where they present large biases that need to be corrected. Our results can also be used to test the models' sensitivity to the day-to-day changing meteorology and to climate change over specific regions.

Missile Defense Information Technology Small Business Conference

DTIC Science & Technology

2009-09-01

NetOps Survivability 4 • Supported User Base • Number of Workstations • Number of Servers • Number of Special Circuits • Number of Sites • Number...Contracts, MDIOC • Ground Test (DTC) • MDSEC (SS) • Infrastructure (IC) • BMDS Support (BCT) • JTAAS – SETA • Mod & Sim ( DES ) • Analysis (GML) • Tenants...AUG 09) 4 MDA DOCE Engineering Functions • Design Engineers – Develop detailed design artifacts based on architectural specifications – Coordinate

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

PubMed

Ogedengbe, O O; Naidu, E C S; Akang, E N; Offor, U; Onanuga, I O; Peter, A I; Jegede, A I; Azu, O O

2018-04-14

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture. © 2018 American Society of Andrology and European Academy of Andrology.

Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.

PubMed

Zhang, Cathy; Yan, Zhengming; Arango, Maria E; Painter, Cory L; Anderes, Kenna

2009-01-01

Tumors grafted s.c. or under the mammary fat pad (MFP) rarely develop efficient metastasis. By applying bioluminescence imaging (BLI) technology, the MDA-MB-435-HAL-Luc subrenal capsule (SRC) model was compared with the MFP model for disease progression, metastatic potential, and response to therapy. The luciferase-expressing MDA-MB-435-HAL-Luc cell line was used in both MFP and SRC models. BLI technology allowed longitudinal assessment of disease progression and the therapeutic response to PD-0332991, Avastin, and docetaxel. Immunohistochemical analysis of Ki67 and CD31 staining in the primary tumors was compared in these models. Caliper measurement was used in the MFP model to validate the BLI quantification of primary tumors. The primary tumors in MDA-MB-435-HAL-Luc MFP and SRC models displayed comparable growth rates and vascularity. However, tumor-bearing mice in the SRC model developed lung metastases much earlier (4 weeks) than in the MFP model (>7 weeks), and the metastatic progression contributed significantly to the survival time. In the MFP model, BLI and caliper measurements were comparable for quantifying palpable tumors, but BLI offered an advantage for detecting the primary tumors that fell below a palpable threshold and for visualizing metastases. In the SRC model, BLI allowed longitudinal assessment of the antitumor and antimetastatic effects of PD-0332991, Avastin, and docetaxel, and the results correlated with the survival benefits of these agents. The MDA-MB-435-HAL-Luc SRC model and the MFP model displayed differences in disease progression. BLI is an innovative approach for developing animal models and creates opportunities for improving preclinical evaluations of anticancer agents.

Integrating Software-Architecture-Centric Methods into the Rational Unified Process

DTIC Science & Technology

2004-07-01

Architecture Design ...................................................................................... 19...QAW in a life- cycle context. One issue that needs to be addressed is how scenarios produced in a QAW can be used by a software architecture design method...implementation testing. 18 CMU/SEI-2004-TR-011 CMU/SEI-2004-TR-011 19 4 Architecture Design The Attribute-Driven Design (ADD) method

Data-driven forecasting of high-dimensional chaotic systems with long short-term memory networks.

PubMed

Vlachas, Pantelis R; Byeon, Wonmin; Wan, Zhong Y; Sapsis, Themistoklis P; Koumoutsakos, Petros

2018-05-01

We introduce a data-driven forecasting method for high-dimensional chaotic systems using long short-term memory (LSTM) recurrent neural networks. The proposed LSTM neural networks perform inference of high-dimensional dynamical systems in their reduced order space and are shown to be an effective set of nonlinear approximators of their attractor. We demonstrate the forecasting performance of the LSTM and compare it with Gaussian processes (GPs) in time series obtained from the Lorenz 96 system, the Kuramoto-Sivashinsky equation and a prototype climate model. The LSTM networks outperform the GPs in short-term forecasting accuracy in all applications considered. A hybrid architecture, extending the LSTM with a mean stochastic model (MSM-LSTM), is proposed to ensure convergence to the invariant measure. This novel hybrid method is fully data-driven and extends the forecasting capabilities of LSTM networks.

Science-Driven Computing: NERSC's Plan for 2006-2010

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

Simon, Horst D.; Kramer, William T.C.; Bailey, David H.

NERSC has developed a five-year strategic plan focusing on three components: Science-Driven Systems, Science-Driven Services, and Science-Driven Analytics. (1) Science-Driven Systems: Balanced introduction of the best new technologies for complete computational systems--computing, storage, networking, visualization and analysis--coupled with the activities necessary to engage vendors in addressing the DOE computational science requirements in their future roadmaps. (2) Science-Driven Services: The entire range of support activities, from high-quality operations and user services to direct scientific support, that enable a broad range of scientists to effectively use NERSC systems in their research. NERSC will concentrate on resources needed to realize the promise ofmore » the new highly scalable architectures for scientific discovery in multidisciplinary computational science projects. (3) Science-Driven Analytics: The architectural and systems enhancements and services required to integrate NERSC's powerful computational and storage resources to provide scientists with new tools to effectively manipulate, visualize, and analyze the huge data sets derived from simulations and experiments.« less

Connected Component Model for Multi-Object Tracking.

PubMed

He, Zhenyu; Li, Xin; You, Xinge; Tao, Dacheng; Tang, Yuan Yan

2016-08-01

In multi-object tracking, it is critical to explore the data associations by exploiting the temporal information from a sequence of frames rather than the information from the adjacent two frames. Since straightforwardly obtaining data associations from multi-frames is an NP-hard multi-dimensional assignment (MDA) problem, most existing methods solve this MDA problem by either developing complicated approximate algorithms, or simplifying MDA as a 2D assignment problem based upon the information extracted only from adjacent frames. In this paper, we show that the relation between associations of two observations is the equivalence relation in the data association problem, based on the spatial-temporal constraint that the trajectories of different objects must be disjoint. Therefore, the MDA problem can be equivalently divided into independent subproblems by equivalence partitioning. In contrast to existing works for solving the MDA problem, we develop a connected component model (CCM) by exploiting the constraints of the data association and the equivalence relation on the constraints. Based upon CCM, we can efficiently obtain the global solution of the MDA problem for multi-object tracking by optimizing a sequence of independent data association subproblems. Experiments on challenging public data sets demonstrate that our algorithm outperforms the state-of-the-art approaches.

Gallium, a promising candidate to disrupt the vicious cycle driving osteolytic metastases.

PubMed

Strazic-Geljic, Ivana; Guberovic, Iva; Didak, Blanka; Schmid-Antomarchi, Heidy; Schmid-Alliana, Annie; Boukhechba, Florian; Bouler, Jean-Michel; Scimeca, Jean-Claude; Verron, Elise

2016-09-15

Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoclastic activity. On the other hand, the semi-metallic element gallium (Ga) displays an inhibitory action on osteoclasts, and therefore on bone resorption, as well as antitumour properties. Thus, we explored in vitro Ga effects on osteoclastogenesis in an aggressive bone metastatic environment based on the culture of pre-osteoclast RAW 264.7 cells with conditioned medium from metastatic breast tumour cells, i.e. the breast tumour cell line model MDA-MB-231 and its bone-seeking clone MDA-231BO. We first observed that Ga dose-dependently inhibited the tumour cells-induced osteoclastic differentiation of RAW 264.7 cells. To mimic a more aggressive environment where pro-tumourigenic factors are released from bone matrix due to osteoclastic resorption, metastatic breast tumour cells were stimulated with TGF-β, a mayor cytokine in bone metastasis vicious cycle. In these conditions, we observed that Ga still inhibited cancer cells-driven osteoclastogenesis. Lastly, we evidenced that Ga affected directly and strongly the proliferation/viability of both cancer cell lines, as well as the expression of major osteolytic factors in MDA-231BO cells. With the exception of two small scale clinical studies from 1980s, this is the first time that antitumour properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for the local treatment of bone metastases in patients with breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Asynchronous Data Retrieval from an Object-Oriented Database

NASA Astrophysics Data System (ADS)

Gilbert, Jonathan P.; Bic, Lubomir

We present an object-oriented semantic database model which, similar to other object-oriented systems, combines the virtues of four concepts: the functional data model, a property inheritance hierarchy, abstract data types and message-driven computation. The main emphasis is on the last of these four concepts. We describe generic procedures that permit queries to be processed in a purely message-driven manner. A database is represented as a network of nodes and directed arcs, in which each node is a logical processing element, capable of communicating with other nodes by exchanging messages. This eliminates the need for shared memory and for centralized control during query processing. Hence, the model is suitable for implementation on a multiprocessor computer architecture, consisting of large numbers of loosely coupled processing elements.

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium.

PubMed

Wang, Yuli; Gunasekara, Dulan B; Reed, Mark I; DiSalvo, Matthew; Bultman, Scott J; Sims, Christopher E; Magness, Scott T; Allbritton, Nancy L

2017-06-01

The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models

PubMed Central

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-01-01

Abstract Background With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. Methods We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Results Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Conclusions Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies. PMID:29860286

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models.

PubMed

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-06-01

With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Conceptual Modeling in the Time of the Revolution: Part II

NASA Astrophysics Data System (ADS)

Mylopoulos, John

Conceptual Modeling was a marginal research topic at the very fringes of Computer Science in the 60s and 70s, when the discipline was dominated by topics focusing on programs, systems and hardware architectures. Over the years, however, the field has moved to centre stage and has come to claim a central role both in Computer Science research and practice in diverse areas, such as Software Engineering, Databases, Information Systems, the Semantic Web, Business Process Management, Service-Oriented Computing, Multi-Agent Systems, Knowledge Management, and more. The transformation was greatly aided by the adoption of standards in modeling languages (e.g., UML), and model-based methodologies (e.g., Model-Driven Architectures) by the Object Management Group (OMG) and other standards organizations. We briefly review the history of the field over the past 40 years, focusing on the evolution of key ideas. We then note some open challenges and report on-going research, covering topics such as the representation of variability in conceptual models, capturing model intentions, and models of laws.

integrated Electronic Health Record Increment 1 (iEHR Inc 1)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Acronyms and Abbreviations ADM - Acquisition Decision Memorandum FD - Full Deployment FDD - Full Deployment Decision iEHR Inc 1 2016 MAR UNCLASSIFIED...iEHR Increment 1 APB for FDD achieved in November 2014 was signed by the MDA March 2, 2015. Current estimate is consistent with the FDD APB. iEHR Inc 1 2016 MAR UNCLASSIFIED 11

Implementing An Image Understanding System Architecture Using Pipe

NASA Astrophysics Data System (ADS)

Luck, Randall L.

1988-03-01

This paper will describe PIPE and how it can be used to implement an image understanding system. Image understanding is the process of developing a description of an image in order to make decisions about its contents. The tasks of image understanding are generally split into low level vision and high level vision. Low level vision is performed by PIPE -a high performance parallel processor with an architecture specifically designed for processing video images at up to 60 fields per second. High level vision is performed by one of several types of serial or parallel computers - depending on the application. An additional processor called ISMAP performs the conversion from iconic image space to symbolic feature space. ISMAP plugs into one of PIPE's slots and is memory mapped into the high level processor. Thus it forms the high speed link between the low and high level vision processors. The mechanisms for bottom-up, data driven processing and top-down, model driven processing are discussed.

A real-time biomimetic acoustic localizing system using time-shared architecture

NASA Astrophysics Data System (ADS)

Nourzad Karl, Marianne; Karl, Christian; Hubbard, Allyn

2008-04-01

In this paper a real-time sound source localizing system is proposed, which is based on previously developed mammalian auditory models. Traditionally, following the models, which use interaural time delay (ITD) estimates, the amount of parallel computations needed by a system to achieve real-time sound source localization is a limiting factor and a design challenge for hardware implementations. Therefore a new approach using a time-shared architecture implementation is introduced. The proposed architecture is a purely sample-base-driven digital system, and it follows closely the continuous-time approach described in the models. Rather than having dedicated hardware on a per frequency channel basis, a specialized core channel, shared for all frequency bands is used. Having an optimized execution time, which is much less than the system's sample rate, the proposed time-shared solution allows the same number of virtual channels to be processed as the dedicated channels in the traditional approach. Hence, the time-shared approach achieves a highly economical and flexible implementation using minimal silicon area. These aspects are particularly important in efficient hardware implementation of a real time biomimetic sound source localization system.

Brahms Mobile Agents: Architecture and Field Tests

NASA Technical Reports Server (NTRS)

Clancey, William J.; Sierhuis, Maarten; Kaskiris, Charis; vanHoof, Ron

2002-01-01

We have developed a model-based, distributed architecture that integrates diverse components in a system designed for lunar and planetary surface operations: an astronaut's space suit, cameras, rover/All-Terrain Vehicle (ATV), robotic assistant, other personnel in a local habitat, and a remote mission support team (with time delay). Software processes, called agents, implemented in the Brahms language, run on multiple, mobile platforms. These mobile agents interpret and transform available data to help people and robotic systems coordinate their actions to make operations more safe and efficient. The Brahms-based mobile agent architecture (MAA) uses a novel combination of agent types so the software agents may understand and facilitate communications between people and between system components. A state-of-the-art spoken dialogue interface is integrated with Brahms models, supporting a speech-driven field observation record and rover command system (e.g., return here later and bring this back to the habitat ). This combination of agents, rover, and model-based spoken dialogue interface constitutes a personal assistant. An important aspect of the methodology involves first simulating the entire system in Brahms, then configuring the agents into a run-time system.

Cloud Computing for Mission Design and Operations

NASA Technical Reports Server (NTRS)

Arrieta, Juan; Attiyah, Amy; Beswick, Robert; Gerasimantos, Dimitrios

2012-01-01

The space mission design and operations community already recognizes the value of cloud computing and virtualization. However, natural and valid concerns, like security, privacy, up-time, and vendor lock-in, have prevented a more widespread and expedited adoption into official workflows. In the interest of alleviating these concerns, we propose a series of guidelines for internally deploying a resource-oriented hub of data and algorithms. These guidelines provide a roadmap for implementing an architecture inspired in the cloud computing model: associative, elastic, semantical, interconnected, and adaptive. The architecture can be summarized as exposing data and algorithms as resource-oriented Web services, coordinated via messaging, and running on virtual machines; it is simple, and based on widely adopted standards, protocols, and tools. The architecture may help reduce common sources of complexity intrinsic to data-driven, collaborative interactions and, most importantly, it may provide the means for teams and agencies to evaluate the cloud computing model in their specific context, with minimal infrastructure changes, and before committing to a specific cloud services provider.

Cascade photonic integrated circuit architecture for electro-optic in-phase quadrature/single sideband modulation or frequency conversion.

PubMed

Hasan, Mehedi; Hall, Trevor

2015-11-01

A photonic integrated circuit architecture for implementing frequency upconversion is proposed. The circuit consists of a 1×2 splitter and 2×1 combiner interconnected by two stages of differentially driven phase modulators having 2×2 multimode interference coupler between the stages. A transfer matrix approach is used to model the operation of the architecture. The predictions of the model are validated by simulations performed using an industry standard software tool. The intrinsic conversion efficiency of the proposed design is improved by 6 dB over the alternative functionally equivalent circuit based on dual parallel Mach-Zehnder modulators known in the prior art. A two-tone analysis is presented to study the linearity of the proposed circuit, and a comparison is provided over the alternative. The proposed circuit is suitable for integration in any platform that offers linear electro-optic phase modulation such as LiNbO(3), silicon, III-V, or hybrid technology.

The Sigma Cognitive Architecture and System: Towards Functionally Elegant Grand Unification

NASA Astrophysics Data System (ADS)

Rosenbloom, Paul S.; Demski, Abram; Ustun, Volkan

2016-12-01

Sigma (Σ) is a cognitive architecture and system whose development is driven by a combination of four desiderata: grand unification, generic cognition, functional elegance, and sufficient efficiency. Work towards these desiderata is guided by the graphical architecture hypothesis, that key to progress on them is combining what has been learned from over three decades' worth of separate work on cognitive architectures and graphical models. In this article, these four desiderata are motivated and explained, and then combined with the graphical architecture hypothesis to yield a rationale for the development of Sigma. The current state of the cognitive architecture is then introduced in detail, along with the graphical architecture that sits below it and implements it. Progress in extending Sigma beyond these architectures and towards a full cognitive system is then detailed in terms of both a systematic set of higher level cognitive idioms that have been developed and several virtual humans that are built from combinations of these idioms. Sigma as a whole is then analyzed in terms of how well the progress to date satisfies the desiderata. This article thus provides the first full motivation, presentation and analysis of Sigma, along with a diversity of more specific results that have been generated during its development.

Spatiotemporal prediction of daily ambient ozone levels across China using random forest for human exposure assessment.

PubMed

Zhan, Yu; Luo, Yuzhou; Deng, Xunfei; Grieneisen, Michael L; Zhang, Minghua; Di, Baofeng

2018-02-01

In China, ozone pollution shows an increasing trend and becomes the primary air pollutant in warm seasons. Leveraging the air quality monitoring network, a random forest model is developed to predict the daily maximum 8-h average ozone concentrations ([O 3 ] MDA8 ) across China in 2015 for human exposure assessment. This model captures the observed spatiotemporal variations of [O 3 ] MDA8 by using the data of meteorology, elevation, and recent-year emission inventories (cross-validation R 2  = 0.69 and RMSE = 26 μg/m 3 ). Compared with chemical transport models that require a plenty of variables and expensive computation, the random forest model shows comparable or higher predictive performance based on only a handful of readily-available variables at much lower computational cost. The nationwide population-weighted [O 3 ] MDA8 is predicted to be 84 ± 23 μg/m 3 annually, with the highest seasonal mean in the summer (103 ± 8 μg/m 3 ). The summer [O 3 ] MDA8 is predicted to be the highest in North China (125 ± 17 μg/m 3 ). Approximately 58% of the population lives in areas with more than 100 nonattainment days ([O 3 ] MDA8 >100 μg/m 3 ), and 12% of the population are exposed to [O 3 ] MDA8 >160 μg/m 3 (WHO Interim Target 1) for more than 30 days. As the most populous zones in China, the Beijing-Tianjin Metro, Yangtze River Delta, Pearl River Delta, and Sichuan Basin are predicted to be at 154, 141, 124, and 98 nonattainment days, respectively. Effective controls of O 3 pollution are urgently needed for the highly-populated zones, especially the Beijing-Tianjin Metro with seasonal [O 3 ] MDA8 of 140 ± 29 μg/m 3 in summer. To the best of the authors' knowledge, this study is the first statistical modeling work of ambient O 3 for China at the national level. This timely and extensively validated [O 3 ] MDA8 dataset is valuable for refining epidemiological analyses on O 3 pollution in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells.

PubMed

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor.

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

PubMed

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

Echo State Networks for data-driven downhole pressure estimation in gas-lift oil wells.

PubMed

Antonelo, Eric A; Camponogara, Eduardo; Foss, Bjarne

2017-01-01

Process measurements are of vital importance for monitoring and control of industrial plants. When we consider offshore oil production platforms, wells that require gas-lift technology to yield oil production from low pressure oil reservoirs can become unstable under some conditions. This undesirable phenomenon is usually called slugging flow, and can be identified by an oscillatory behavior of the downhole pressure measurement. Given the importance of this measurement and the unreliability of the related sensor, this work aims at designing data-driven soft-sensors for downhole pressure estimation in two contexts: one for speeding up first-principle model simulation of a vertical riser model; and another for estimating the downhole pressure using real-world data from an oil well from Petrobras based only on topside platform measurements. Both tasks are tackled by employing Echo State Networks (ESN) as an efficient technique for training Recurrent Neural Networks. We show that a single ESN is capable of robustly modeling both the slugging flow behavior and a steady state based only on a square wave input signal representing the production choke opening in the vertical riser. Besides, we compare the performance of a standard network to the performance of a multiple timescale hierarchical architecture in the second task and show that the latter architecture performs better in modeling both large irregular transients and more commonly occurring small oscillations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Affordable non-traditional source data mining for context assessment to improve distributed fusion system robustness

NASA Astrophysics Data System (ADS)

Bowman, Christopher; Haith, Gary; Steinberg, Alan; Morefield, Charles; Morefield, Michael

2013-05-01

This paper describes methods to affordably improve the robustness of distributed fusion systems by opportunistically leveraging non-traditional data sources. Adaptive methods help find relevant data, create models, and characterize the model quality. These methods also can measure the conformity of this non-traditional data with fusion system products including situation modeling and mission impact prediction. Non-traditional data can improve the quantity, quality, availability, timeliness, and diversity of the baseline fusion system sources and therefore can improve prediction and estimation accuracy and robustness at all levels of fusion. Techniques are described that automatically learn to characterize and search non-traditional contextual data to enable operators integrate the data with the high-level fusion systems and ontologies. These techniques apply the extension of the Data Fusion & Resource Management Dual Node Network (DNN) technical architecture at Level 4. The DNN architecture supports effectively assessment and management of the expanded portfolio of data sources, entities of interest, models, and algorithms including data pattern discovery and context conformity. Affordable model-driven and data-driven data mining methods to discover unknown models from non-traditional and `big data' sources are used to automatically learn entity behaviors and correlations with fusion products, [14 and 15]. This paper describes our context assessment software development, and the demonstration of context assessment of non-traditional data to compare to an intelligence surveillance and reconnaissance fusion product based upon an IED POIs workflow.

Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

PubMed

Tien, Joe; Truslow, James G; Nelson, Celeste M

2012-01-01

This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

A new software-based architecture for quantum computer

NASA Astrophysics Data System (ADS)

Wu, Nan; Song, FangMin; Li, Xiangdong

2010-04-01

In this paper, we study a reliable architecture of a quantum computer and a new instruction set and machine language for the architecture, which can improve the performance and reduce the cost of the quantum computing. We also try to address some key issues in detail in the software-driven universal quantum computers.

Applying MDA to SDR for Space to Model Real-time Issues

NASA Technical Reports Server (NTRS)

Blaser, Tammy M.

2007-01-01

NASA space communications systems have the challenge of designing SDRs with highly-constrained Size, Weight and Power (SWaP) resources. A study is being conducted to assess the effectiveness of applying the MDA Platform-Independent Model (PIM) and one or more Platform-Specific Models (PSM) specifically to address NASA space domain real-time issues. This paper will summarize our experiences with applying MDA to SDR for Space to model real-time issues. Real-time issues to be examined, measured, and analyzed are: meeting waveform timing requirements and efficiently applying Real-time Operating System (RTOS) scheduling algorithms, applying safety control measures, and SWaP verification. Real-time waveform algorithms benchmarked with the worst case environment conditions under the heaviest workload will drive the SDR for Space real-time PSM design.

Transforming growth factor expression (TGF-β) correlate with serum level of malondialdehyde (MDA) after EVOO administration in preclinical rat models of preeclampsia

NASA Astrophysics Data System (ADS)

Ilyas, Syafruddin; Hutahaean, Salomo; Evi Irianti, dan

2018-03-01

Preeclampsia can cause cell death either apoptosis or necrosis. One cause is the disturbance of the emergence of malondialdehyde (MDA). Very few reports on the role of Transforming Growth Factor Expression (TGF-β) in the remodeling process of placental cells and their association with serum MDA content. Research of true experiment with complete randomized design (CRD) with five treatment groups. The first group, preeclampsia negative control (T0). The second group, preeclamptic rats model (T1). The third group, preeclamptic rats model+EVOO 0.45g/kg-Body Weight/day (T2). The fourth group, preeclamptic rats model+EVOO 0.90g/kg-BW/day (T3). The fifth group, preeclamptic rats model+EVOO 1.8 g/kg-BW/day (T4). The results showed a significant effect of EVOO on TGF-β expression in preeclampsia rats, meaning that there was a role of TGF-β against pre-eclampsia placenta remodeling. There was a positive and strong relationship (r=0.494) as well as a very significant relationship (p<0.01) between TGF-β and the serum MDA.

Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution.

PubMed

Gai, Zuoqi; Matsuno, Asuka; Kato, Koji; Kato, Sanae; Khan, Md Rafiqul Islam; Shimizu, Takeshi; Yoshioka, Takeya; Kato, Yuki; Kishimura, Hideki; Kanno, Gaku; Miyabe, Yoshikatsu; Terada, Tohru; Tanaka, Yoshikazu; Yao, Min

2015-12-01

Molluscan hemocyanin, a copper-containing oxygen transporter, is one of the largest known proteins. Although molluscan hemocyanins are currently applied as immunotherapeutic agents, their precise structure has not been determined because of their enormous size. Here, we have determined the first X-ray crystal structure of intact molluscan hemocyanin. The structure unveiled the architecture of the 3.8-MDa supermolecule composed of homologous functional units (FUs), wherein the dimers of FUs hierarchically associated to form the entire cylindrical decamer. Most of the specific inter-FU interactions were localized at narrow regions in the FU dimers, suggesting that rigid FU dimers formed by specific interactions assemble with flexibility. Furthermore, the roles of carbohydrates in assembly and allosteric effect, and conserved sulfur-containing residues in copper incorporation, were revealed. The precise structural information obtained in this study will accelerate our understanding of the molecular basis of hemocyanin and its future applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S.

PubMed

Younis, Nahla N; Shaheen, Mohamed A; Mahmoud, Mona F

2016-08-01

Hydrogen sulfide (H2S) can protect against hepatic ischemia-reperfusion injury (HIR). However, it is unknown whether it can protect against HIR in insulin resistance. This study investigated the protective effects of silymarin against HIR in a rat model of insulin resistance and the possible involvement of endogenous H2S. Insulin resistance was first established using 10% fructose in drinking water for 10 weeks. HIR was conducted in fructose-fed rats treated with saline or silymarin (100 mg/kg), 15 min before HIR (30 min ischemia, followed by 1 h reperfusion). Insulin resistance and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), total nitrites (NO2(-)), and H2S were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), hydroxyproline, H2S synthesizing activity, and mRNA expression of cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) were determined. Additionally, histopathological examination involved H&E, Sirius red, and caspase-3 immunostaining. Fructose-induced insulin resistance increased serum ALT, TNF-α, H2S and H2S synthesizing activity, and hepatic MDA, hydroxyproline, and CSE mRNA and decreased NO2(-) and GSH. These changes exacerbated the HIR injury in which endogenous H2S production was auxiliary increased. Silymarin preconditioning decreased ALT, AST, MDA, NO2(-), TNF-α, and TNF-α/IL-10 ratio, increased GSH, IL-10, improved hepatic architecture, and lowered caspase-3 immunostaining. Serum H2S, its hepatic synthesizing activity, and CSE and CBS mRNA expressions were all suppressed by silymarin pretreatment. The increases in endogenous H2S exacerbate HIR injury, whereas silymarin preconditioning protected against HIR in insulin resistant rats via powerful antioxidant, anti-inflammatory, and antiapoptotic effects along with suppressing H2S production. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of the Collaborative Optimization Architecture for Launch Vehicle Design

NASA Technical Reports Server (NTRS)

Braun, R. D.; Moore, A. A.; Kroo, I. M.

1996-01-01

Collaborative optimization is a new design architecture specifically created for large-scale distributed-analysis applications. In this approach, problem is decomposed into a user-defined number of subspace optimization problems that are driven towards interdisciplinary compatibility and the appropriate solution by a system-level coordination process. This decentralized design strategy allows domain-specific issues to be accommodated by disciplinary analysts, while requiring interdisciplinary decisions to be reached by consensus. The present investigation focuses on application of the collaborative optimization architecture to the multidisciplinary design of a single-stage-to-orbit launch vehicle. Vehicle design, trajectory, and cost issues are directly modeled. Posed to suit the collaborative architecture, the design problem is characterized by 5 design variables and 16 constraints. Numerous collaborative solutions are obtained. Comparison of these solutions demonstrates the influence which an priori ascent-abort criterion has on development cost. Similarly, objective-function selection is discussed, demonstrating the difference between minimum weight and minimum cost concepts. The operational advantages of the collaborative optimization

R516Q mutation in Melanoma differentiation-associated protein 5 (MDA5) and its pathogenic role towards rare Singleton-Merten syndrome; a signature associated molecular dynamics study.

PubMed

Raghuraman, P; Sudandiradoss, C

2018-02-20

Singleton-Merten syndrome, a critical and rare multifactorial disorder that is closely linked to R516Q mutation in MDA5 protein associated with an enhanced interferon response in the affected individual. In the present study, we provide conclusive key evidence on R516Q mutation and their connectivity towards sequence-structural basis dysfunction of MDA5 protein. Among the various mutations, we found R516Q is the most pathogenic mutation based on mutational signature Q-A-[RE]-G-R-[GA]-R-A-[ED]-[DE]-S-[ST]-Y-[TSAV]-L-V designed from our work. Further, we derived a distant ortholog for this mutational signature from which we identified 343 intra-residue interactions that fall communally in the position required to maintain the structural and functional integration of protein architecture. This identification served us to understand the critical role of hot spots in residual aggregation that holds a native form of folding conformation in the functional region. In addition, the long-range molecular dynamics simulation demarcated the residual dependencies of conformational transition in distinct regions ( L29 360-370 α18 , α19 380-410 L31 , α21 430-480 L33-α22-L35 and α24 510-520 L38 ) occurring upon R516Q mutation. Together, our results emphasise that the dislocation of functional hot spots Pro229, Arg414, Val498, Met510, Ala513, Gly515 and Arg516 in MDA5 protein which is important for interior structural packing and fold arrangements. In a nutshell, our findings are perfectly conceded with other experimental reports and will have potential implications in immune therapeutical advancement for rare singleton-merten syndrome.

Probabilistic Forecasting of Surface Ozone with a Novel Statistical Approach

NASA Technical Reports Server (NTRS)

Balashov, Nikolay V.; Thompson, Anne M.; Young, George S.

2017-01-01

The recent change in the Environmental Protection Agency's surface ozone regulation, lowering the surface ozone daily maximum 8-h average (MDA8) exceedance threshold from 75 to 70 ppbv, poses significant challenges to U.S. air quality (AQ) forecasters responsible for ozone MDA8 forecasts. The forecasters, supplied by only a few AQ model products, end up relying heavily on self-developed tools. To help U.S. AQ forecasters, this study explores a surface ozone MDA8 forecasting tool that is based solely on statistical methods and standard meteorological variables from the numerical weather prediction (NWP) models. The model combines the self-organizing map (SOM), which is a clustering technique, with a step wise weighted quadratic regression using meteorological variables as predictors for ozone MDA8. The SOM method identifies different weather regimes, to distinguish between various modes of ozone variability, and groups them according to similarity. In this way, when a regression is developed for a specific regime, data from the other regimes are also used, with weights that are based on their similarity to this specific regime. This approach, regression in SOM (REGiS), yields a distinct model for each regime taking into account both the training cases for that regime and other similar training cases. To produce probabilistic MDA8 ozone forecasts, REGiS weighs and combines all of the developed regression models on the basis of the weather patterns predicted by an NWP model. REGiS is evaluated over the San Joaquin Valley in California and the northeastern plains of Colorado. The results suggest that the model performs best when trained and adjusted separately for an individual AQ station and its corresponding meteorological site.

Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models.

PubMed

Tullberg, Cecilia; Larsson, Karin; Carlsson, Nils-Gunnar; Comi, Irene; Scheers, Nathalie; Vegarud, Gerd; Undeland, Ingrid

2016-03-01

In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy-trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 μM of MDA, 0.96 μM of HHE, and 1.6 μM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 μM of MDA; 0.16, and 0.026 μM of HHE; 0.23, and 0.005 μM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies.

The structure of human tripeptidyl peptidase II as determined by a hybrid approach.

PubMed

Schönegge, Anne-Marie; Villa, Elizabeth; Förster, Friedrich; Hegerl, Reiner; Peters, Jürgen; Baumeister, Wolfgang; Rockel, Beate

2012-04-04

Tripeptidyl-peptidase II (TPPII) is a high molecular mass (∼5 MDa) serine protease, which is thought to act downstream of the 26S proteasome, cleaving peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has been determined to subnanometer resolution by cryoelectron microscopy and single-particle analysis. The complex is built from two strands forming a quasihelical structure harboring a complex system of inner cavities. HsTPPII particles exhibit some polymorphism resulting in complexes consisting of nine or of eight dimers per strand. To obtain deeper insights into the architecture and function of HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a comparative model of HsTPPII dimers and molecular dynamics flexible fitting. Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optimal Design of Cable-Driven Manipulators Using Particle Swarm Optimization.

PubMed

Bryson, Joshua T; Jin, Xin; Agrawal, Sunil K

2016-08-01

The design of cable-driven manipulators is complicated by the unidirectional nature of the cables, which results in extra actuators and limited workspaces. Furthermore, the particular arrangement of the cables and the geometry of the robot pose have a significant effect on the cable tension required to effect a desired joint torque. For a sufficiently complex robot, the identification of a satisfactory cable architecture can be difficult and can result in multiply redundant actuators and performance limitations based on workspace size and cable tensions. This work leverages previous research into the workspace analysis of cable systems combined with stochastic optimization to develop a generalized methodology for designing optimized cable routings for a given robot and desired task. A cable-driven robot leg performing a walking-gait motion is used as a motivating example to illustrate the methodology application. The components of the methodology are described, and the process is applied to the example problem. An optimal cable routing is identified, which provides the necessary controllable workspace to perform the desired task and enables the robot to perform that task with minimal cable tensions. A robot leg is constructed according to this routing and used to validate the theoretical model and to demonstrate the effectiveness of the resulting cable architecture.

Macro-actor execution on multilevel data-driven architectures

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

Gaudiot, J.L.; Najjar, W.

1988-12-31

The data-flow model of computation brings to multiprocessors high programmability at the expense of increased overhead. Applying the model at a higher level leads to better performance but also introduces loss of parallelism. We demonstrate here syntax directed program decomposition methods for the creation of large macro-actors in numerical algorithms. In order to alleviate some of the problems introduced by the lower resolution interpretation, we describe a multi-level of resolution and analyze the requirements for its actual hardware and software integration.

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research

PubMed Central

Amin, Waqas; Singh, Harpreet; Pople, Andre K.; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V.; Becich, Michael J.

2010-01-01

Context: Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Design: Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. Result: The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. Conclusion: These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems. PMID:20922029

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research.

PubMed

Amin, Waqas; Singh, Harpreet; Pople, Andre K; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V; Becich, Michael J

2010-08-10

Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

PubMed Central

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Introduction Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. Methods MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. Results The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. Conclusion The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor. PMID:15987447

Models for Experimental High Density Housing

NASA Astrophysics Data System (ADS)

Bradecki, Tomasz; Swoboda, Julia; Nowak, Katarzyna; Dziechciarz, Klaudia

2017-10-01

The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio - housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.

The Rasch Model and Missing Data, with an Emphasis on Tailoring Test Items.

ERIC Educational Resources Information Center

de Gruijter, Dato N. M.

Many applications of educational testing have a missing data aspect (MDA). This MDA is perhaps most pronounced in item banking, where each examinee responds to a different subtest of items from a large item pool and where both person and item parameter estimates are needed. The Rasch model is emphasized, and its non-parametric counterpart (the…

Modeling the Economic and Epidemiologic Impact of Hookworm Vaccine and Mass Drug Administration (MDA) in Brazil, a High Transmission Setting

PubMed Central

Bartsch, Sarah M.; Hotez, Peter J.; Hertenstein, Daniel L.; Diemert, David J.; Zapf, Kristina M.; Bottazzi, Maria Elena; Bethony, Jeffrey M.; Brown, Shawn T.; Lee, Bruce Y.

2017-01-01

Background Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. Methods We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Results Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤$790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤$444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) than annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0%, nearly eliminated hookworm infection in children. Conclusion Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally. PMID:27002501

Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting.

PubMed

Bartsch, Sarah M; Hotez, Peter J; Hertenstein, Daniel L; Diemert, David J; Zapf, Kristina M; Bottazzi, Maria Elena; Bethony, Jeffrey M; Brown, Shawn T; Lee, Bruce Y

2016-04-27

Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤ $790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤ $444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) versus annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0% and nearly eliminated hookworm infection in children. Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally. Copyright © 2016 Elsevier Ltd. All rights reserved.

An architecture for a continuous, user-driven, and data-driven application of clinical guidelines and its evaluation.

PubMed

Shalom, Erez; Shahar, Yuval; Lunenfeld, Eitan

2016-02-01

Design, implement, and evaluate a new architecture for realistic continuous guideline (GL)-based decision support, based on a series of requirements that we have identified, such as support for continuous care, for multiple task types, and for data-driven and user-driven modes. We designed and implemented a new continuous GL-based support architecture, PICARD, which accesses a temporal reasoning engine, and provides several different types of application interfaces. We present the new architecture in detail in the current paper. To evaluate the architecture, we first performed a technical evaluation of the PICARD architecture, using 19 simulated scenarios in the preeclampsia/toxemia domain. We then performed a functional evaluation with the help of two domain experts, by generating patient records that simulate 60 decision points from six clinical guideline-based scenarios, lasting from two days to four weeks. Finally, 36 clinicians made manual decisions in half of the scenarios, and had access to the automated GL-based support in the other half. The measures used in all three experiments were correctness and completeness of the decisions relative to the GL. Mean correctness and completeness in the technical evaluation were 1±0.0 and 0.96±0.03 respectively. The functional evaluation produced only several minor comments from the two experts, mostly regarding the output's style; otherwise the system's recommendations were validated. In the clinically oriented evaluation, the 36 clinicians applied manually approximately 41% of the GL's recommended actions. Completeness increased to approximately 93% when using PICARD. Manual correctness was approximately 94.5%, and remained similar when using PICARD; but while 68% of the manual decisions included correct but redundant actions, only 3% of the actions included in decisions made when using PICARD were redundant. The PICARD architecture is technically feasible and is functionally valid, and addresses the realistic continuous GL-based application requirements that we have defined; in particular, the requirement for care over significant time frames. The use of the PICARD architecture in the domain we examined resulted in enhanced completeness and in reduction of redundancies, and is potentially beneficial for general GL-based management of chronic patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Schematic driven layout of Reed Solomon encoders

NASA Technical Reports Server (NTRS)

Arave, Kari; Canaris, John; Miles, Lowell; Whitaker, Sterling

1992-01-01

Two Reed Solomon error correcting encoders are presented. Schematic driven layout tools were used to create the encoder layouts. Special consideration had to be given to the architecture and logic to provide scalability of the encoder designs. Knowledge gained from these projects was used to create a more flexible schematic driven layout system.

Lifelong learning of human actions with deep neural network self-organization.

PubMed

Parisi, German I; Tani, Jun; Weber, Cornelius; Wermter, Stefan

2017-12-01

Lifelong learning is fundamental in autonomous robotics for the acquisition and fine-tuning of knowledge through experience. However, conventional deep neural models for action recognition from videos do not account for lifelong learning but rather learn a batch of training data with a predefined number of action classes and samples. Thus, there is the need to develop learning systems with the ability to incrementally process available perceptual cues and to adapt their responses over time. We propose a self-organizing neural architecture for incrementally learning to classify human actions from video sequences. The architecture comprises growing self-organizing networks equipped with recurrent neurons for processing time-varying patterns. We use a set of hierarchically arranged recurrent networks for the unsupervised learning of action representations with increasingly large spatiotemporal receptive fields. Lifelong learning is achieved in terms of prediction-driven neural dynamics in which the growth and the adaptation of the recurrent networks are driven by their capability to reconstruct temporally ordered input sequences. Experimental results on a classification task using two action benchmark datasets show that our model is competitive with state-of-the-art methods for batch learning also when a significant number of sample labels are missing or corrupted during training sessions. Additional experiments show the ability of our model to adapt to non-stationary input avoiding catastrophic interference. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The emergence of overlapping scale-free genetic architecture in digital organisms.

PubMed

Gerlee, P; Lundh, T

2008-01-01

We have studied the evolution of genetic architecture in digital organisms and found that the gene overlap follows a scale-free distribution, which is commonly found in metabolic networks of many organisms. Our results show that the slope of the scale-free distribution depends on the mutation rate and that the gene development is driven by expansion of already existing genes, which is in direct correspondence to the preferential growth algorithm that gives rise to scale-free networks. To further validate our results we have constructed a simple model of gene development, which recapitulates the results from the evolutionary process and shows that the mutation rate affects the tendency of genes to cluster. In addition we could relate the slope of the scale-free distribution to the genetic complexity of the organisms and show that a high mutation rate gives rise to a more complex genetic architecture.

Strategic Defense Initiative (SDI) System Architecture and Key Tradeoff Studies, Phase IIC, IDEF0 Functional Decomposition Flows; Appendix D

DTIC Science & Technology

1988-03-15

Number: MDA903-85-C-0065 Document Type: HC Number of Copies In Library : 000001 Record ID: 21248 o o I CO CO I Q CO CO r ^ CO 5 Q o CO...8217 • eg 2 CO <D 2? il n S.2 I a 0) c? *- CD a C3i.t fit mooc I- Q_ 8 £ CO « 3 Sa CO o F* c JS a. »| s-s CD U CO •o 2

Advanced and secure architectural EHR approaches.

PubMed

Blobel, Bernd

2006-01-01

Electronic Health Records (EHRs) provided as a lifelong patient record advance towards core applications of distributed and co-operating health information systems and health networks. For meeting the challenge of scalable, flexible, portable, secure EHR systems, the underlying EHR architecture must be based on the component paradigm and model driven, separating platform-independent and platform-specific models. Allowing manageable models, real systems must be decomposed and simplified. The resulting modelling approach has to follow the ISO Reference Model - Open Distributing Processing (RM-ODP). The ISO RM-ODP describes any system component from different perspectives. Platform-independent perspectives contain the enterprise view (business process, policies, scenarios, use cases), the information view (classes and associations) and the computational view (composition and decomposition), whereas platform-specific perspectives concern the engineering view (physical distribution and realisation) and the technology view (implementation details from protocols up to education and training) on system components. Those views have to be established for components reflecting aspects of all domains involved in healthcare environments including administrative, legal, medical, technical, etc. Thus, security-related component models reflecting all view mentioned have to be established for enabling both application and communication security services as integral part of the system's architecture. Beside decomposition and simplification of system regarding the different viewpoint on their components, different levels of systems' granularity can be defined hiding internals or focusing on properties of basic components to form a more complex structure. The resulting models describe both structure and behaviour of component-based systems. The described approach has been deployed in different projects defining EHR systems and their underlying architectural principles. In that context, the Australian GEHR project, the openEHR initiative, the revision of CEN ENV 13606 "Electronic Health Record communication", all based on Archetypes, but also the HL7 version 3 activities are discussed in some detail. The latter include the HL7 RIM, the HL7 Development Framework, the HL7's clinical document architecture (CDA) as well as the set of models from use cases, activity diagrams, sequence diagrams up to Domain Information Models (DMIMs) and their building blocks Common Message Element Types (CMET) Constraining Models to their underlying concepts. The future-proof EHR architecture as open, user-centric, user-friendly, flexible, scalable, portable core application in health information systems and health networks has to follow advanced architectural paradigms.

Quantifying O3 Impacts in Urban Areas Due to Wildfires Using a Generalized Additive Model.

PubMed

Gong, Xi; Kaulfus, Aaron; Nair, Udaysankar; Jaffe, Daniel A

2017-11-21

Wildfires emit O 3 precursors but there are large variations in emissions, plume heights, and photochemical processing. These factors make it challenging to model O 3 production from wildfires using Eulerian models. Here we describe a statistical approach to characterize the maximum daily 8-h average O 3 (MDA8) for 8 cities in the U.S. for typical, nonfire, conditions. The statistical model represents between 35% and 81% of the variance in MDA8 for each city. We then examine the residual from the model under conditions with elevated particulate matter (PM) and satellite observed smoke ("smoke days"). For these days, the residuals are elevated by an average of 3-8 ppb (MDA8) compared to nonsmoke days. We found that while smoke days are only 4.1% of all days (May-Sept) they are 19% of days with an MDA8 greater than 75 ppb. We also show that a published method that does not account for transport patterns gives rise to large overestimates in the amount of O 3 from fires, particularly for coastal cities. Finally, we apply this method to a case study from August 2015, and show that the method gives results that are directly applicable to the EPA guidance on excluding data due to an uncontrollable source.

A Spiking Neural Simulator Integrating Event-Driven and Time-Driven Computation Schemes Using Parallel CPU-GPU Co-Processing: A Case Study.

PubMed

Naveros, Francisco; Luque, Niceto R; Garrido, Jesús A; Carrillo, Richard R; Anguita, Mancia; Ros, Eduardo

2015-07-01

Time-driven simulation methods in traditional CPU architectures perform well and precisely when simulating small-scale spiking neural networks. Nevertheless, they still have drawbacks when simulating large-scale systems. Conversely, event-driven simulation methods in CPUs and time-driven simulation methods in graphic processing units (GPUs) can outperform CPU time-driven methods under certain conditions. With this performance improvement in mind, we have developed an event-and-time-driven spiking neural network simulator suitable for a hybrid CPU-GPU platform. Our neural simulator is able to efficiently simulate bio-inspired spiking neural networks consisting of different neural models, which can be distributed heterogeneously in both small layers and large layers or subsystems. For the sake of efficiency, the low-activity parts of the neural network can be simulated in CPU using event-driven methods while the high-activity subsystems can be simulated in either CPU (a few neurons) or GPU (thousands or millions of neurons) using time-driven methods. In this brief, we have undertaken a comparative study of these different simulation methods. For benchmarking the different simulation methods and platforms, we have used a cerebellar-inspired neural-network model consisting of a very dense granular layer and a Purkinje layer with a smaller number of cells (according to biological ratios). Thus, this cerebellar-like network includes a dense diverging neural layer (increasing the dimensionality of its internal representation and sparse coding) and a converging neural layer (integration) similar to many other biologically inspired and also artificial neural networks.

Modeling the Sedimentary Infill of Lakes in the East African Rift: A Case Study of Multiple versus Single Rift Basin Segments

NASA Astrophysics Data System (ADS)

Zhang, C.; Scholz, C. A.

2016-12-01

The sedimentary basins in the East African Rift are considered excellent modern examples for investigating sedimentary infilling and evolution of extensional systems. Some lakes in the western branch of the rift have formed within single-segment systems, and include Lake Albert and Lake Edward. The largest and oldest lakes developed within multi-segment systems, and these include Lake Tanganyika and Lake Malawi. This research aims to explore processes of erosion and sedimentary infilling of the catchment area in single-segment rift (SSR) and multi-segment rift (MSR) systems. We consider different conditions of regional precipitation and evaporation, and assess the resulting facies architecture through forward modeling, using state-of-the-art commercial basin modeling software. Dionisos is a three-dimensional numerical stratigraphic forward modeling software program, which simulates basin-scale sediment transport based on empirical water- and gravity-driven diffusion equations. It was classically used to quantify the sedimentary architecture and basin infilling of both marine siliciclastic and carbonate environments. However, we apply this approach to continental rift basin environments. In this research, two scenarios are developed, one for a MSR and the other for a SSR. The modeled systems simulate the ratio of drainage area and lake surface area observed in modern Lake Tanganyika and Lake Albert, which are examples of MSRs and SSRs, respectively. The main parameters, such as maximum subsidence rate, water- and gravity-driven diffusion coefficients, rainfall, and evaporation, are approximated using these real-world examples. The results of 5 million year model runs with 50,000 year time steps show that MSRs are characterized by a deep water lake with relatively modest sediment accumulation, while the SSRs are characterized by a nearly overfilled lake with shallow water depths and thick sediment accumulation. The preliminary modeling results conform to the features of sedimentary infills revealed by seismic reflection data acquired in Lake Tanganyika and Lake Albert. Future models will refine the parameters of rainfall and evaporation in these two scenarios to better evaluate detailed basin facies architecture.

Implementing partnership-driven clinical federated electronic health record data sharing networks.

PubMed

Stephens, Kari A; Anderson, Nicholas; Lin, Ching-Ping; Estiri, Hossein

2016-09-01

Building federated data sharing architectures requires supporting a range of data owners, effective and validated semantic alignment between data resources, and consistent focus on end-users. Establishing these resources requires development methodologies that support internal validation of data extraction and translation processes, sustaining meaningful partnerships, and delivering clear and measurable system utility. We describe findings from two federated data sharing case examples that detail critical factors, shared outcomes, and production environment results. Two federated data sharing pilot architectures developed to support network-based research associated with the University of Washington's Institute of Translational Health Sciences provided the basis for the findings. A spiral model for implementation and evaluation was used to structure iterations of development and support knowledge share between the two network development teams, which cross collaborated to support and manage common stages. We found that using a spiral model of software development and multiple cycles of iteration was effective in achieving early network design goals. Both networks required time and resource intensive efforts to establish a trusted environment to create the data sharing architectures. Both networks were challenged by the need for adaptive use cases to define and test utility. An iterative cyclical model of development provided a process for developing trust with data partners and refining the design, and supported measureable success in the development of new federated data sharing architectures. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts: implications for development of an atheroprotective vaccine1[S

PubMed Central

Gonen, Ayelet; Hansen, Lotte F.; Turner, William W.; Montano, Erica N.; Que, Xuchu; Rafia, Apaїs; Chou, Meng-Yun; Wiesner, Philipp; Tsiantoulas, Dimitrios; Corr, Maripat; VanNieuwenhze, Michael S.; Tsimikas, Sotirios; Binder, Christoph J.; Witztum, Joseph L.; Hartvigsen, Karsten

2014-01-01

Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought to determine the responsible immunodominant and atheroprotective adducts. We now demonstrate that fluorescent adducts of MDA involving the condensation of two or more MDA molecules with lysine to form malondialdehyde-acetaldehyde (MAA)-type adducts generate immunodominant epitopes that lead to atheroprotective responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do not target relevant antigens. These data demonstrate the feasibility of development of a small-molecule immunogen that could stimulate MAA-specific immune responses, which could be used to develop a vaccine approach to retard or prevent atherogenesis. PMID:25143462

A Multi-mission Event-Driven Component-Based System for Support of Flight Software Development, ATLO, and Operations first used by the Mars Science Laboratory (MSL) Project

NASA Technical Reports Server (NTRS)

Dehghani, Navid; Tankenson, Michael

2006-01-01

This paper details an architectural description of the Mission Data Processing and Control System (MPCS), an event-driven, multi-mission ground data processing components providing uplink, downlink, and data management capabilities which will support the Mars Science Laboratory (MSL) project as its first target mission. MPCS is developed based on a set of small reusable components, implemented in Java, each designed with a specific function and well-defined interfaces. An industry standard messaging bus is used to transfer information among system components. Components generate standard messages which are used to capture system information, as well as triggers to support the event-driven architecture of the system. Event-driven systems are highly desirable for processing high-rate telemetry (science and engineering) data, and for supporting automation for many mission operations processes.

A synchronized computational architecture for generalized bilateral control of robot arms

NASA Technical Reports Server (NTRS)

Bejczy, Antal K.; Szakaly, Zoltan

1987-01-01

This paper describes a computational architecture for an interconnected high speed distributed computing system for generalized bilateral control of robot arms. The key method of the architecture is the use of fully synchronized, interrupt driven software. Since an objective of the development is to utilize the processing resources efficiently, the synchronization is done in the hardware level to reduce system software overhead. The architecture also achieves a balaced load on the communication channel. The paper also describes some architectural relations to trading or sharing manual and automatic control.

System on chip module configured for event-driven architecture

DOEpatents

Robbins, Kevin; Brady, Charles E.; Ashlock, Tad A.

2017-10-17

A system on chip (SoC) module is described herein, wherein the SoC modules comprise a processor subsystem and a hardware logic subsystem. The processor subsystem and hardware logic subsystem are in communication with one another, and transmit event messages between one another. The processor subsystem executes software actors, while the hardware logic subsystem includes hardware actors, the software actors and hardware actors conform to an event-driven architecture, such that the software actors receive and generate event messages and the hardware actors receive and generate event messages.

Equilibria, prudent compromises, and the "waiting" game.

PubMed

Sim, Kwang Mong

2005-08-01

While evaluation of many e-negotiation agents are carried out through empirical studies, this work supplements and complements existing literature by analyzing the problem of designing market-driven agents (MDAs) in terms of equilibrium points and stable strategies. MDAs are negotiation agents designed to make prudent compromises taking into account factors such as time preference, outside option, and rivalry. This work shows that 1) in a given market situation, an MDA negotiates optimally because it makes minimally sufficient concession, and 2) by modeling negotiation of MDAs as a game gamma of incomplete information, it is shown that the strategies adopted by MDAs are stable. In a bilateral negotiation, it is proven that the strategy pair of two MDAs forms a sequential equilibrium for gamma. In a multilateral negotiation, it is shown that the strategy profile of MDAs forms a market equilibrium for gamma.

[Effects of electroacupuncture of "Sanyinjiao" (SP 6) on contents of MDA and beta-EP, and expression of HSP 70 in the uterus in rats with dysmenorrhea].

PubMed

Song, Xiao-Lin; Zhang, Lu-Fen; Li, Xiao-Hong; Xu, Li-Li; Li, Chun-Hua; Ding, Xi-Yan; Ren, Xiao-Xuan; Zhao, Ya-Fang; Guo, Meng-Wei; Sun, Zhi-Fang; Zhu, Jiang

2010-10-01

To investigate the effect of electroacupuncture (EA) of "Sanyinjiao" (SP 6) on the uterus in dysmenorrhea rats so as to study its underlying analgesic mechanism. A total of 48 SD rats during diestrus were randomized into normal saline (control) group, model group and acupuncture group according to a random number table, with 16 rats in each group. Dysmenorrhea model was established by subcutaneous injection of Estradiol benzoate (0.5 mg/d on the 1st and 10th day, and 0.2 mg/d from day 2 to day 9, once daily for 10 days) and oxytocin (2 U/rat, once on day 10). Malondialdehyde (MDA) and beta-endorphin (beta-EP) contents in the uterus were detected by radioimmunoassay, and the heat shock protein 70 (HSP 70) immunoactivity of the uterus was detected by immunohistochemistry. In comparison with the control group, MDA content in the uterus was increased significantly in the model group (P < 0.01), while the beta-EP level and the immunoactivity of HSP 70 immune-reaction (IR) positive products in the uterus decrease significantly (P < 0.01) and moderately, respectively in the model group. In comparison with the model group, uterine MDA content in the EA group was decreased significantly (P < 0.01), while uterine beta-EP level increased considerably (P < 0.01) and HSP 70 expression was upregulated to a certain degree. EA of "Sanyinjiao" (SP 6) can reduce MDA content and upregulate beta-EP level of the uterus in rats with dysmenorrhea, which may contribute to its analgesic effect in relieving dysmenorrhea by clearing away oxygen free radicals and raising analgesic substance in the uterus.

Quantifying errors in surface ozone predictions associated with clouds over the CONUS: a WRF-Chem modeling study using satellite cloud retrievals

NASA Astrophysics Data System (ADS)

Ryu, Young-Hee; Hodzic, Alma; Barre, Jerome; Descombes, Gael; Minnis, Patrick

2018-05-01

Clouds play a key role in radiation and hence O3 photochemistry by modulating photolysis rates and light-dependent emissions of biogenic volatile organic compounds (BVOCs). It is not well known, however, how much error in O3 predictions can be directly attributed to error in cloud predictions. This study applies the Weather Research and Forecasting with Chemistry (WRF-Chem) model at 12 km horizontal resolution with the Morrison microphysics and Grell 3-D cumulus parameterization to quantify uncertainties in summertime surface O3 predictions associated with cloudiness over the contiguous United States (CONUS). All model simulations are driven by reanalysis of atmospheric data and reinitialized every 2 days. In sensitivity simulations, cloud fields used for photochemistry are corrected based on satellite cloud retrievals. The results show that WRF-Chem predicts about 55 % of clouds in the right locations and generally underpredicts cloud optical depths. These errors in cloud predictions can lead to up to 60 ppb of overestimation in hourly surface O3 concentrations on some days. The average difference in summertime surface O3 concentrations derived from the modeled clouds and satellite clouds ranges from 1 to 5 ppb for maximum daily 8 h average O3 (MDA8 O3) over the CONUS. This represents up to ˜ 40 % of the total MDA8 O3 bias under cloudy conditions in the tested model version. Surface O3 concentrations are sensitive to cloud errors mainly through the calculation of photolysis rates (for ˜ 80 %), and to a lesser extent to light-dependent BVOC emissions. The sensitivity of surface O3 concentrations to satellite-based cloud corrections is about 2 times larger in VOC-limited than NOx-limited regimes. Our results suggest that the benefits of accurate predictions of cloudiness would be significant in VOC-limited regions, which are typical of urban areas.

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication

PubMed Central

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro, overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated (P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway. PMID:28194372

LncITPRIP-1 Positively Regulates Innate Immune Response through Promoting Oligomerization and Activation of MDA5.

PubMed

Xie, Qinya; Chen, Shengwen; Tian, Renyun; Huang, Xiang; Deng, Rilin; Xue, Binbin; Qin, Yuwen; Xu, Yan; Wang, Jingjing; Guo, Mengmeng; Chen, Jinwen; Tang, Songqing; Li, Guangdi; Zhu, Haizhen

2018-06-13

Emerging evidence indicates that long non-coding RNAs (lncRNAs) regulate various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and interferon (IFN) pathway remains largely unknown. Here, we report that lncRNA ITPRIP-1 (lncITPRIP-1) is involved in viral infection and plays a crucial role in virus-triggered IFN signaling pathway through targeting MDA5. LncITPRIP-1 can be induced by viral infection, which is not entirely dependent on IFN signal. Besides, there is no coding potential found in lncITPRIP-1 transcript. LncITPRIP-1 binds to the C-terminal of MDA5 and it possesses the ability to boost oligomerization of both full length and 2CARD domains of MDA5 in a K63-linked-polyubiquitination-independent manner. Amazingly, we also find that MDA5 could suppress HCV replication independent of IFN signaling through its C-terminal deficient domain bound to viral RNA, in which lncITPRIP-1 plays as an assistant. In addition, the expression of lncITPRIP-1 is highly consistent with MDA5 expression, indicating that lncITPRIP-1 may function as a cofactor of MDA5. All the data suggest that lncITPRIP-1 enhances innate immune response to viral infection through promoting oligomerization and activation of MDA5. Our study discovers the first lncRNA ITPRIP-1 involved in MDA5 activation. SIGNIFICANCE Hepatitis C virus infection causes a global health issue and there is still no available vaccine, which makes it urgent to reveal the underlying mechanisms of HCV and host factors. Although RIG-I has been recognized as the leading cytoplasmic sensor against HCV for a long time, recent findings of MDA5 regulating IFN response to HCV have emerged. Our work validates the significant role of MDA5 in IFN signaling and HCV infection, and proposes the first lncRNA inhibiting HCV replication by promoting the activation of MDA5 and mediating the association between MDA5 and HCV RNA, which may shed light on MDA5 function study and the treatment for hepatitis C patients. Our suggested model of how lncITPRIP-1 can orchestrate signal transduction for IFN production illustrates the essential role of lncRNAs in virus elimination. Copyright © 2018 American Society for Microbiology.

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication.

PubMed

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 ( MDA5 ) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro , overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated ( P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol.

PubMed

Ásbjörnsdóttir, Kristjana Hrönn; Ajjampur, Sitara S Rao; Anderson, Roy M; Bailey, Robin; Gardiner, Iain; Halliday, Katherine E; Ibikounle, Moudachirou; Kalua, Khumbo; Kang, Gagandeep; Littlewood, D Timothy J; Luty, Adrian J F; Means, Arianna Rubin; Oswald, William; Pullan, Rachel L; Sarkar, Rajiv; Schär, Fabian; Szpiro, Adam; Truscott, James E; Werkman, Marleen; Yard, Elodie; Walson, Judd L

2018-01-01

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. ClinicalTrials.gov NCT03014167.

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa

PubMed Central

Chesnais, Cédric B.; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K.; Boussinesq, Michel; Fischer, Peter U.; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D.

2017-01-01

Background The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. Methodology The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Principal findings Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. Conclusions/Significance This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance. PMID:28892473

Novel Role of MDA-9/Syntenin in Regulating Urothelial Cell Proliferation by Modulating EGFR Signaling

PubMed Central

Dasgupta, Santanu; Menezes, Mitchell E.; Das, Swadesh K.; Emdad, Luni; Janjic, Aleksandar; Bhatia, Shilpa; Mukhopadhyay, Nitai D; Shao, Chunbo; Sarkar, Devanand; Fisher, Paul B.

2013-01-01

Purpose Urothelial cell carcinoma (UCC) rapidly progresses from superficial to muscle-invasive tumors. The key molecules involved in metastatic progression and its early detection require clarification. The present study defines a seminal role of the metastasis-associated gene MDA-9/Syntenin in UCC progression. Experimental Design Expression pattern of MDA-9/Syntenin was examined in 44 primary UCC and the impact of its overexpression and knock down was examined in multiple cells lines and key findings were validated in primary tumors. Results Significantly higher (p= 0.002–0.003) expression of MDA-9/Syntenin was observed in 64% (28/44) of primary tumors and an association was evident with stage (p=0.01), grade (p=0.03) and invasion status (p=0.02). MDA-9/Syntenin overexpression in non-tumorigenic HUC-1 cells increased proliferation (p=0.0012), invasion (p=0.0001) and EGFR, AKT, PI3K and c-Src expression. Alteration of Beta-catenin, E-Cadherin, Vimentin, Claudin-1, ZO-1 and TCF4 expression were also observed. MDA-9/Syntenin knock down in 3 UCC cell lines reversed phenotypic and molecular changes observed in the HUC-1 cells and reduced in vivo metastasis. Key molecular changes observed in the cell lines were confirmed in primary tumors. A physical interaction and co-localization of MDA-9/Syntenin and EGFR was evident in UCC cell lines and primary tumors. A logistic regression model analysis revealed a significant correlation between MDA-9/Syntenin:EGFR and MDA-9/Syntenin: AKT expressions with stage (p=0.04, EGFR), (p=0.01, AKT). A correlation between MDA-9/Syntenin: β-catenin co-expression with stage (p=0.03) and invasion (p=0.04) was also evident. Conclusions Our findings indicate that MDA-9/Syntenin might provide an attractive target for developing detection, monitoring and therapeutic strategies for managing UCC. PMID:23873690

Novel role of MDA-9/syntenin in regulating urothelial cell proliferation by modulating EGFR signaling.

PubMed

Dasgupta, Santanu; Menezes, Mitchell E; Das, Swadesh K; Emdad, Luni; Janjic, Aleksandar; Bhatia, Shilpa; Mukhopadhyay, Nitai D; Shao, Chunbo; Sarkar, Devanand; Fisher, Paul B

2013-09-01

Urothelial cell carcinoma (UCC) rapidly progresses from superficial to muscle-invasive tumors. The key molecules involved in metastatic progression and its early detection require clarification. The present study defines a seminal role of the metastasis-associated gene MDA-9/Syntenin in UCC progression. Expression pattern of MDA-9/Syntenin was examined in 44 primary UCC and the impact of its overexpression and knockdown was examined in multiple cells lines and key findings were validated in primary tumors. Significantly higher (P=0.002-0.003) expression of MDA-9/Syntenin was observed in 64% (28 of 44) of primary tumors and an association was evident with stage (P=0.01), grade (P=0.03), and invasion status (P=0.02). MDA-9/Syntenin overexpression in nontumorigenic HUC-1 cells increased proliferation (P=0.0012), invasion (P=0.0001), and EGF receptor (EGFR), AKT, phosphoinositide 3-kinase (PI3K), and c-Src expression. Alteration of β-catenin, E-cadherin, vimentin, claudin-1, ZO-1, and T-cell factor-4 (TCF4) expression was also observed. MDA-9/Syntenin knockdown in three UCC cell lines reversed phenotypic and molecular changes observed in the HUC-1 cells and reduced in vivo metastasis. Key molecular changes observed in the cell lines were confirmed in primary tumors. A physical interaction and colocalization of MDA-9/Syntenin and EGFR was evident in UCC cell lines and primary tumors. A logistic regression model analysis revealed a significant correlation between MDA-9/Syntenin:EGFR and MDA-9/Syntenin:AKT expressions with stage (P=0.04, EGFR; P=0.01, AKT). A correlation between MDA-9/Syntenin:β-catenin coexpression with stage (P=0.03) and invasion (P=0.04) was also evident. Our findings indicate that MDA-9/Syntenin might provide an attractive target for developing detection, monitoring, and therapeutic strategies for managing UCC. ©2013 AACR.

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa.

PubMed

Chesnais, Cédric B; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K; Boussinesq, Michel; Fischer, Peter U; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D; Weil, Gary J

2017-09-01

The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance.

[Study on effect of jinshui liujun jian oral liquid on serum superoxide dismutase activity and malonyldialdehyde content in mice with chronic bronchitis].

PubMed

Zhao, C Y; Shen, Y S; Meng, H

2001-11-01

To study the effect of Jinshui Liujun Jian Oral Liquid (JLJOL) on serum superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) content in mice with chronic bronchitis. JLJOL was given to the chronic bronchitis mice model (induced by smoking) through gastrogavage, and then SOD activity and MDA content were tested. SOD activity in model mice after JLJOL treatment was 0.67 +/- 0.15 NU/L, which was significantly higher than that in the untreated model (0.39 +/- 0.13 NU/L, P < 0.01). But the MDA content in treated mice was significantly lower than that in untreated one (9.26 +/- 2.90 nmol/L vs 16.07 +/- 5.62 nmol/L, P < 0.01). JLJOL could scavenge the injury of free radical on organism.

Therapeutic effects of autologous lymphocytes activated with trastuzumab for xenograft mouse models of human breast cancer.

PubMed

Nakagawa, Shinichiro; Matsuoka, Yusuke; Ichihara, Hideaki; Yoshida, Hitoji; Yoshida, Kenshi; Ueoka, Ryuichi

2013-01-01

Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK) using xenograft mouse models of human breast cancer (MDA-MB-453) cells were examined in vivo. Remarkable reduction of tumor volume in a xenograft mouse models intravenously treated with TTZ-LAK cells after the subcutaneously inoculated of MDA-MB-453 cells was verified in vivo. The migration of TTZ-LAK cells in tumor of mouse models subcutaneously inoculated MDA-MB-453 cells was observed on the basis of histological analysis using immunostaining with CD-3. Induction of apoptosis in tumor of xenograft mice treated with TTZ-LAK cells was observed in micrographs using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. It was noteworthy that the therapeutic effects of TTZ-LAK cells along with apoptosis were obtained for xenograft mouse models of human breast tumor in vivo.

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

PubMed Central

2010-01-01

Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

Table-driven software architecture for a stitching system

NASA Technical Reports Server (NTRS)

Thrash, Patrick J. (Inventor); Miller, Jeffrey L. (Inventor); Pallas, Ken (Inventor); Trank, Robert C. (Inventor); Fox, Rhoda (Inventor); Korte, Mike (Inventor); Codos, Richard (Inventor); Korolev, Alexandre (Inventor); Collan, William (Inventor)

2001-01-01

Native code for a CNC stitching machine is generated by generating a geometry model of a preform; generating tool paths from the geometry model, the tool paths including stitching instructions for making stitches; and generating additional instructions indicating thickness values. The thickness values are obtained from a lookup table. When the stitching machine runs the native code, it accesses a lookup table to determine a thread tension value corresponding to the thickness value. The stitching machine accesses another lookup table to determine a thread path geometry value corresponding to the thickness value.

Defining and using open architecture levels

NASA Astrophysics Data System (ADS)

Cramer, M. A.; Morrison, A. W.; Cordes, B.; Stack, J. R.

2012-05-01

Open architecture (OA) within military systems enables delivery of increased warfighter capabilities in a shorter time at a reduced cost.i In fact in today's standards-aware environment, solutions are often proposed to the government that include OA as one of its basics design tenets. Yet the ability to measure and assess OA in an objective manner, particularly at the subsystem/component level within a system, remains an elusive proposition. Furthermore, it is increasingly apparent that the establishment of an innovation ecosystem of an open business model that leverages thirdparty development requires more than just technical modifications that promote openness. This paper proposes a framework to migrate not only towards technical openness, but also towards enabling and facilitating an open business model, driven by third party development, for military systems. This framework was developed originally for the U.S. Navy Littoral and Mine Warfare community; however, the principles and approach may be applied elsewhere within the Navy and Department of Defense.

MALDI-Mass Spectrometric Imaging Revealing Hypoxia-Driven Lipids and Proteins in a Breast Tumor Model

DOE PAGES

Jiang, Lu; Chughtai, Kamila; Purvine, Samuel O.; ...

2015-05-20

Hypoxic areas are a common feature of rapidly growing malignant tumors and their metastases, and are typically spatially heterogeneous. Hypoxia has a strong impact on tumor cell biology and contributes to tumor progression in multiple ways. To date, only a few molecular key players in tumor hypoxia, such as for example hypoxia-inducible factor-1 (HIF-1), have been discovered. The distribution of biomolecules is frequently heterogeneous in the tumor volume, and may be driven by hypoxia and HIF-1α. Understanding the spatially heterogeneous hypoxic response of tumors is critical. Mass spectrometric imaging (MSI) provides a unique way of imaging biomolecular distributions in tissuemore » sections with high spectral and spatial resolution. In this paper, breast tumor xenografts grown from MDA-MB-231-HRE-tdTomato cells, with a red fluorescent tdTomato protein construct under the control of a hypoxia response element (HRE)-containing promoter driven by HIF-1α, were used to detect the spatial distribution of hypoxic regions. We elucidated the 3D spatial relationship between hypoxic regions and the localization of small molecules, metabolites, lipids, and proteins by using principal component analysis – linear discriminant analysis (PCA-LDA) on 3D rendered MSI volume data from MDA-MB-231-HRE-tdTomato breast tumor xenografts. In this study we identified hypoxia-regulated proteins active in several distinct pathways such as glucose metabolism, regulation of actin cytoskeleton, protein folding, translation/ribosome, splicesome, the PI3K-Akt signaling pathway, hemoglobin chaperone, protein processing in endoplasmic reticulum, detoxification of reactive oxygen species, aurora B signaling/apoptotic execution phase, the RAS signaling pathway, the FAS signaling pathway/caspase cascade in apoptosis and telomere stress induced senescence. In parallel we also identified co-localization of hypoxic regions and various lipid species such as PC(16:0/18:1), PC(16:0/18:2), PC(18:0/18:1), PC(18:1/18:1), PC(18:1/18:2), PC(16:1/18:4), PC(18:0/20:3), PC(16:0/22:1), among others. Lastly, our findings shed light on the biomolecular composition of hypoxic tumor regions, which may be responsible for a given tumor’s resistance to radiation or chemotherapy.« less

MALDI-Mass Spectrometric Imaging Revealing Hypoxia-Driven Lipids and Proteins in a Breast Tumor Model

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

Jiang, Lu; Chughtai, Kamila; Purvine, Samuel O.

Hypoxic areas are a common feature of rapidly growing malignant tumors and their metastases, and are typically spatially heterogeneous. Hypoxia has a strong impact on tumor cell biology and contributes to tumor progression in multiple ways. To date, only a few molecular key players in tumor hypoxia, such as for example hypoxia-inducible factor-1 (HIF-1), have been discovered. The distribution of biomolecules is frequently heterogeneous in the tumor volume, and may be driven by hypoxia and HIF-1α. Understanding the spatially heterogeneous hypoxic response of tumors is critical. Mass spectrometric imaging (MSI) provides a unique way of imaging biomolecular distributions in tissuemore » sections with high spectral and spatial resolution. In this paper, breast tumor xenografts grown from MDA-MB-231-HRE-tdTomato cells, with a red fluorescent tdTomato protein construct under the control of a hypoxia response element (HRE)-containing promoter driven by HIF-1α, were used to detect the spatial distribution of hypoxic regions. We elucidated the 3D spatial relationship between hypoxic regions and the localization of small molecules, metabolites, lipids, and proteins by using principal component analysis – linear discriminant analysis (PCA-LDA) on 3D rendered MSI volume data from MDA-MB-231-HRE-tdTomato breast tumor xenografts. In this study we identified hypoxia-regulated proteins active in several distinct pathways such as glucose metabolism, regulation of actin cytoskeleton, protein folding, translation/ribosome, splicesome, the PI3K-Akt signaling pathway, hemoglobin chaperone, protein processing in endoplasmic reticulum, detoxification of reactive oxygen species, aurora B signaling/apoptotic execution phase, the RAS signaling pathway, the FAS signaling pathway/caspase cascade in apoptosis and telomere stress induced senescence. In parallel we also identified co-localization of hypoxic regions and various lipid species such as PC(16:0/18:1), PC(16:0/18:2), PC(18:0/18:1), PC(18:1/18:1), PC(18:1/18:2), PC(16:1/18:4), PC(18:0/20:3), PC(16:0/22:1), among others. Lastly, our findings shed light on the biomolecular composition of hypoxic tumor regions, which may be responsible for a given tumor’s resistance to radiation or chemotherapy.« less

Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia?

PubMed

Miyata, T; Fu, M X; Kurokawa, K; van Ypersele de Strihou, C; Thorpe, S R; Baynes, J W

1998-10-01

Advanced glycation end products (AGEs), formed by non-enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (P < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.

A methodology for the validated design space exploration of fuel cell powered unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Moffitt, Blake Almy

Unmanned Aerial Vehicles (UAVs) are the most dynamic growth sector of the aerospace industry today. The need to provide persistent intelligence, surveillance, and reconnaissance for military operations is driving the planned acquisition of over 5,000 UAVs over the next five years. The most pressing need is for quiet, small UAVs with endurance beyond what is capable with advanced batteries or small internal combustion propulsion systems. Fuel cell systems demonstrate high efficiency, high specific energy, low noise, low temperature operation, modularity, and rapid refuelability making them a promising enabler of the small, quiet, and persistent UAVs that military planners are seeking. Despite the perceived benefits, the actual near-term performance of fuel cell powered UAVs is unknown. Until the auto industry began spending billions of dollars in research, fuel cell systems were too heavy for useful flight applications. However, the last decade has seen rapid development with fuel cell gravimetric and volumetric power density nearly doubling every 2--3 years. As a result, a few design studies and demonstrator aircraft have appeared, but overall the design methodology and vehicles are still in their infancy. The design of fuel cell aircraft poses many challenges. Fuel cells differ fundamentally from combustion based propulsion in how they generate power and interact with other aircraft subsystems. As a result, traditional multidisciplinary analysis (MDA) codes are inappropriate. Building new MDAs is difficult since fuel cells are rapidly changing in design, and various competitive architectures exist for balance of plant, hydrogen storage, and all electric aircraft subsystems. In addition, fuel cell design and performance data is closely protected which makes validation difficult and uncertainty significant. Finally, low specific power and high volumes compared to traditional combustion based propulsion result in more highly constrained design spaces that are problematic for design space exploration. To begin addressing the current gaps in fuel cell aircraft development, a methodology has been developed to explore and characterize the near-term performance of fuel cell powered UAVs. The first step of the methodology is the development of a valid MDA. This is accomplished by using propagated uncertainty estimates to guide the decomposition of a MDA into key contributing analyses (CAs) that can be individually refined and validated to increase the overall accuracy of the MDA. To assist in MDA development, a flexible framework for simultaneously solving the CAs is specified. This enables the MDA to be easily adapted to changes in technology and the changes in data that occur throughout a design process. Various CAs that model a polymer electrolyte membrane fuel cell (PEMFC) UAV are developed, validated, and shown to be in agreement with hardware-in-the-loop simulations of a fully developed fuel cell propulsion system. After creating a valid MDA, the final step of the methodology is the synthesis of the MDA with an uncertainty propagation analysis, an optimization routine, and a chance constrained problem formulation. This synthesis allows an efficient calculation of the probabilistic constraint boundaries and Pareto frontiers that will govern the design space and influence design decisions relating to optimization and uncertainty mitigation. A key element of the methodology is uncertainty propagation. The methodology uses Systems Sensitivity Analysis (SSA) to estimate the uncertainty of key performance metrics due to uncertainties in design variables and uncertainties in the accuracy of the CAs. A summary of SSA is provided and key rules for properly decomposing a MDA for use with SSA are provided. Verification of SSA uncertainty estimates via Monte Carlo simulations is provided for both an example problem as well as a detailed MDA of a fuel cell UAV. Implementation of the methodology was performed on a small fuel cell UAV designed to carry a 2.2 kg payload with 24 hours of endurance. Uncertainty distributions for both design variables and the CAs were estimated based on experimental results and were found to dominate the design space. To reduce uncertainty and test the flexibility of the MDA framework, CAs were replaced with either empirical, or semi-empirical relationships during the optimization process. The final design was validated via a hardware-in-the loop simulation. Finally, the fuel cell UAV probabilistic design space was studied. A graphical representation of the design space was generated and the optima due to deterministic and probabilistic constraints were identified. The methodology was used to identify Pareto frontiers of the design space which were shown on contour plots of the design space. Unanticipated discontinuities of the Pareto fronts were observed as different constraints became active providing useful information on which to base design and development decisions.

Method to suppress DDFS spurious signals in a frequency-hopping synthesizer with DDFS-driven PLL architecture.

PubMed

Kwon, Kun-Sup; Yoon, Won-Sang

2010-01-01

In this paper we propose a method of removing from synthesizer output spurious signals due to quasi-amplitude modulation and superposition effect in a frequency-hopping synthesizer with direct digital frequency synthesizer (DDFS)-driven phase-locked loop (PLL) architecture, which has the advantages of high frequency resolution, fast transition time, and small size. There are spurious signals that depend on normalized frequency of DDFS. They can be dominant if they occur within the PLL loop bandwidth. We suggest that such signals can be eliminated by purposefully creating frequency errors in the developed synthesizer.

Reference architecture of application services for personal wellbeing information management.

PubMed

Tuomainen, Mika; Mykkänen, Juha

2011-01-01

Personal information management has been proposed as an important enabler for individual empowerment concerning citizens' wellbeing and health information. In the MyWellbeing project in Finland, a strictly citizen-driven concept of "Coper" and related architectural and functional guidelines have been specified. We present a reference architecture and a set of identified application services to support personal wellbeing information management. In addition, the related standards and developments are discussed.

Reference architecture and interoperability model for data mining and fusion in scientific cross-domain infrastructures

NASA Astrophysics Data System (ADS)

Haener, Rainer; Waechter, Joachim; Grellet, Sylvain; Robida, Francois

2017-04-01

Interoperability is the key factor in establishing scientific research environments and infrastructures, as well as in bringing together heterogeneous, geographically distributed risk management, monitoring, and early warning systems. Based on developments within the European Plate Observing System (EPOS), a reference architecture has been devised that comprises architectural blue-prints and interoperability models regarding the specification of business processes and logic as well as the encoding of data, metadata, and semantics. The architectural blueprint is developed on the basis of the so called service-oriented architecture (SOA) 2.0 paradigm, which combines intelligence and proactiveness of event-driven with service-oriented architectures. SOA 2.0 supports analysing (Data Mining) both, static and real-time data in order to find correlations of disparate information that do not at first appear to be intuitively obvious: Analysed data (e.g., seismological monitoring) can be enhanced with relationships discovered by associating them (Data Fusion) with other data (e.g., creepmeter monitoring), with digital models of geological structures, or with the simulation of geological processes. The interoperability model describes the information, communication (conversations) and the interactions (choreographies) of all participants involved as well as the processes for registering, providing, and retrieving information. It is based on the principles of functional integration, implemented via dedicated services, communicating via service-oriented and message-driven infrastructures. The services provide their functionality via standardised interfaces: Instead of requesting data directly, users share data via services that are built upon specific adapters. This approach replaces the tight coupling at data level by a flexible dependency on loosely coupled services. The main component of the interoperability model is the comprehensive semantic description of the information, business logic and processes on the basis of a minimal set of well-known, established standards. It implements the representation of knowledge with the application of domain-controlled vocabularies to statements about resources, information, facts, and complex matters (ontologies). Seismic experts for example, would be interested in geological models or borehole measurements at a certain depth, based on which it is possible to correlate and verify seismic profiles. The entire model is built upon standards from the Open Geospatial Consortium (Dictionaries, Service Layer), the International Organisation for Standardisation (Registries, Metadata), and the World Wide Web Consortium (Resource Description Framework, Spatial Data on the Web Best Practices). It has to be emphasised that this approach is scalable to the greatest possible extent: All information, necessary in the context of cross-domain infrastructures is referenced via vocabularies and knowledge bases containing statements that provide either the information itself or resources (service-endpoints), the information can be retrieved from. The entire infrastructure communication is subject to a broker-based business logic integration platform where the information exchanged between involved participants, is managed on the basis of standardised dictionaries, repositories, and registries. This approach also enables the development of Systems-of-Systems (SoS), which allow the collaboration of autonomous, large scale concurrent, and distributed systems, yet cooperatively interacting as a collective in a common environment.

Prediction model of velocity field around circular cylinder over various Reynolds numbers by fusion convolutional neural networks based on pressure on the cylinder

NASA Astrophysics Data System (ADS)

Jin, Xiaowei; Cheng, Peng; Chen, Wen-Li; Li, Hui

2018-04-01

A data-driven model is proposed for the prediction of the velocity field around a cylinder by fusion convolutional neural networks (CNNs) using measurements of the pressure field on the cylinder. The model is based on the close relationship between the Reynolds stresses in the wake, the wake formation length, and the base pressure. Numerical simulations of flow around a cylinder at various Reynolds numbers are carried out to establish a dataset capturing the effect of the Reynolds number on various flow properties. The time series of pressure fluctuations on the cylinder is converted into a grid-like spatial-temporal topology to be handled as the input of a CNN. A CNN architecture composed of a fusion of paths with and without a pooling layer is designed. This architecture can capture both accurate spatial-temporal information and the features that are invariant of small translations in the temporal dimension of pressure fluctuations on the cylinder. The CNN is trained using the computational fluid dynamics (CFD) dataset to establish the mapping relationship between the pressure fluctuations on the cylinder and the velocity field around the cylinder. Adam (adaptive moment estimation), an efficient method for processing large-scale and high-dimensional machine learning problems, is employed to implement the optimization algorithm. The trained model is then tested over various Reynolds numbers. The predictions of this model are found to agree well with the CFD results, and the data-driven model successfully learns the underlying flow regimes, i.e., the relationship between wake structure and pressure experienced on the surface of a cylinder is well established.

Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

PubMed

Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

2015-01-01

Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line

PubMed Central

Di Venere, Donato

2015-01-01

Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16INK4a and p21Cip1/Waf1 in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy. PMID:26180585

In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells

PubMed Central

Hembach, Katharina; Baum, Alina; García-Sastre, Adolfo; Söding, Johannes; Conzelmann, Karl-Klaus

2014-01-01

RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5′-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling. PMID:24743923

Data to Decisions: Creating a Culture of Model-Driven Drug Discovery.

PubMed

Brown, Frank K; Kopti, Farida; Chang, Charlie Zhenyu; Johnson, Scott A; Glick, Meir; Waller, Chris L

2017-09-01

Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a "model-driven" culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a "Design Cycle" that makes use of all the data possible, internally and externally, to drive decision-making. These data can take the form of bioactivity, 3D structures, genomics, pathway, PK/PD, safety data, etc. Synthesis of high-quality data into models utilizing both well-established and cutting-edge methods has been shown to yield high confidence predictions to prioritize decision-making and efficiently reposition resources within R&D. The goal is to design an adaptive research operating plan that uses both modeled data and experiments, rather than just testing, to drive project decision-making. To support this emerging culture, an ambitious information management (IT) program has been initiated to implement a harmonized platform to facilitate the construction of cross-domain workflows to enable data-driven decision-making and the construction and validation of predictive models. These goals are achieved through depositing model-ready data, agile persona-driven access to data, a unified cross-domain predictive model lifecycle management platform, and support for flexible scientist-developed workflows that simplify data manipulation and consume model services. The end-to-end nature of the platform, in turn, not only supports but also drives the culture change by enabling scientists to apply predictive sciences throughout their work and over the lifetime of a project. This shift in mindset for both scientists and IT was driven by an early impactful demonstration of the potential benefits of the platform, in which expert-level early discovery predictive models were made available from familiar desktop tools, such as ChemDraw. This was built using a workflow-driven service-oriented architecture (SOA) on top of the rigorous registration of all underlying model entities.

Porting plasma physics simulation codes to modern computing architectures using the libmrc framework

NASA Astrophysics Data System (ADS)

Germaschewski, Kai; Abbott, Stephen

2015-11-01

Available computing power has continued to grow exponentially even after single-core performance satured in the last decade. The increase has since been driven by more parallelism, both using more cores and having more parallelism in each core, e.g. in GPUs and Intel Xeon Phi. Adapting existing plasma physics codes is challenging, in particular as there is no single programming model that covers current and future architectures. We will introduce the open-source libmrc framework that has been used to modularize and port three plasma physics codes: The extended MHD code MRCv3 with implicit time integration and curvilinear grids; the OpenGGCM global magnetosphere model; and the particle-in-cell code PSC. libmrc consolidates basic functionality needed for simulations based on structured grids (I/O, load balancing, time integrators), and also introduces a parallel object model that makes it possible to maintain multiple implementations of computational kernels, on e.g. conventional processors and GPUs. It handles data layout conversions and enables us to port performance-critical parts of a code to a new architecture step-by-step, while the rest of the code can remain unchanged. We will show examples of the performance gains and some physics applications.

2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.

PubMed

Singhal, Jyotsana; Nagaprashantha, Lokesh; Chikara, Shireen; Awasthi, Sanjay; Horne, David; Singhal, Sharad S

2017-09-26

Breast cancer is the most common cancer in women that is driven by cross-talk with hormonal and cellular signaling pathways. The natural phytochemicals, due to broad-spectrum anti-inflammatory and anti-cancerous properties, present with novel opportunities for targeting breast cancer. Intake of citrus fruits is known to reduce the risk for incidence of breast cancer. Hence, we tested the efficacy of citrus flavonoid 2'-hydroxyflavanone (2HF) in breast cancer. 2HF inhibited survival, clonogenic ability, cell cycle progression and induced apoptosis in breast cancer cells. 2HF also decreased VEGF levels and inhibited migratory capacity of breast cancer cells. Administration of 2HF led to regression of triple-negative MDA-MB-231 tumors in the mice xenograft model. 2HF decreased the levels of RLIP76 both in vitro studies and in vivo MDA-MB-231 xenograft model of breast cancer. Western blot and histopathological analyses of resected tumors showed a decline in the levels of survival and proliferation markers Ki67, pAkt, survivin, and cell cycle proteins CDK4 and cyclin B1. 2HF treatment led to inhibition of angiogenesis as determined by decreased VEGF levels in vitro and angiogenesis marker CD31 in vivo . 2HF reversed the pro-/anti-apoptotic ratio of BAX/BCL-2 by decreasing anti-apoptotic protein BCL-2 and increasing pro-apoptotic proteins BAX and BIM in vivo . 2HF also decreased the mesenchymal markers vimentin and fibronectin along with causing a parallel increase in pro-differentiation protein E-cadherin. Collectively, the ability of 2HF to decrease RLIP76, VEGF and regulate critical proliferative, apoptotic and differentiation proteins together provides strong rationale to further develop 2HF based interventions for targeting breast cancer.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol

PubMed Central

Ajjampur, Sitara S. Rao; Anderson, Roy M.; Bailey, Robin; Gardiner, Iain; Halliday, Katherine E.; Ibikounle, Moudachirou; Kalua, Khumbo; Kang, Gagandeep; Littlewood, D. Timothy J.; Luty, Adrian J. F.; Means, Arianna Rubin; Oswald, William; Pullan, Rachel L.; Sarkar, Rajiv; Schär, Fabian; Szpiro, Adam; Truscott, James E.; Werkman, Marleen; Yard, Elodie; Walson, Judd L.

2018-01-01

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. Trial registration ClinicalTrials.gov NCT03014167 PMID:29346377

MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib.

PubMed

Young, Adelaide I J; Law, Andrew M K; Castillo, Lesley; Chong, Sabrina; Cullen, Hayley D; Koehler, Martin; Herzog, Sebastian; Brummer, Tilman; Lee, Erinna F; Fairlie, Walter D; Lucas, Morghan C; Herrmann, David; Allam, Amr; Timpson, Paul; Watkins, D Neil; Millar, Ewan K A; O'Toole, Sandra A; Gallego-Ortega, David; Ormandy, Christopher J; Oakes, Samantha R

2016-12-08

Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells. MCL-1 inhibition caused apoptosis of basal-like MDA-MB-468-2A cells grown as monolayers, and sensitized them to the BCL-2/BCL-XL inhibitor ABT-263, demonstrating that MCL-1 regulated cell survival. In MDA-MB-231-2A cells, grown in an organotypic model, induction of BIMs2A produced an almost complete suppression of invasion. Apoptosis was induced in such a small proportion of these cells that it could not account for the large decrease in invasion, suggesting that MCL-1 was operating via a previously undetected mechanism. MCL-1 antagonism also suppressed local invasion and distant metastasis to the lung in mouse mammary intraductal xenografts. Kinomic profiling revealed that MCL-1 antagonism modulated Src family kinases and their targets, which suggested that MCL-1 might act as an upstream modulator of invasion via this pathway. Inhibition of MCL-1 in combination with dasatinib suppressed invasion in 3D models of invasion and inhibited the establishment of tumors in vivo. These data provide the first evidence that MCL-1 drives breast cancer cell invasion and suggests that MCL-1 antagonists could be used alone or in combination with drugs targeting Src kinases such as dasatinib to suppress metastasis.

Can We Practically Bring Physics-based Modeling Into Operational Analytics Tools?

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

Granderson, Jessica; Bonvini, Marco; Piette, Mary Ann

We present that analytics software is increasingly used to improve and maintain operational efficiency in commercial buildings. Energy managers, owners, and operators are using a diversity of commercial offerings often referred to as Energy Information Systems, Fault Detection and Diagnostic (FDD) systems, or more broadly Energy Management and Information Systems, to cost-effectively enable savings on the order of ten to twenty percent. Most of these systems use data from meters and sensors, with rule-based and/or data-driven models to characterize system and building behavior. In contrast, physics-based modeling uses first-principles and engineering models (e.g., efficiency curves) to characterize system and buildingmore » behavior. Historically, these physics-based approaches have been used in the design phase of the building life cycle or in retrofit analyses. Researchers have begun exploring the benefits of integrating physics-based models with operational data analytics tools, bridging the gap between design and operations. In this paper, we detail the development and operator use of a software tool that uses hybrid data-driven and physics-based approaches to cooling plant FDD and optimization. Specifically, we describe the system architecture, models, and FDD and optimization algorithms; advantages and disadvantages with respect to purely data-driven approaches; and practical implications for scaling and replicating these techniques. Finally, we conclude with an evaluation of the future potential for such tools and future research opportunities.« less

The dynamics of architectural complexity on coral reefs under climate change.

PubMed

Bozec, Yves-Marie; Alvarez-Filip, Lorenzo; Mumby, Peter J

2015-01-01

One striking feature of coral reef ecosystems is the complex benthic architecture which supports diverse and abundant fauna, particularly of reef fish. Reef-building corals are in decline worldwide, with a corresponding loss of live coral cover resulting in a loss of architectural complexity. Understanding the dynamics of the reef architecture is therefore important to envision the ability of corals to maintain functional habitats in an era of climate change. Here, we develop a mechanistic model of reef topographical complexity for contemporary Caribbean reefs. The model describes the dynamics of corals and other benthic taxa under climate-driven disturbances (hurricanes and coral bleaching). Corals have a simplified shape with explicit diameter and height, allowing species-specific calculation of their colony surface and volume. Growth and the mechanical (hurricanes) and biological erosion (parrotfish) of carbonate skeletons are important in driving the pace of extension/reduction in the upper reef surface, the net outcome being quantified by a simple surface roughness index (reef rugosity). The model accurately simulated the decadal changes of coral cover observed in Cozumel (Mexico) between 1984 and 2008, and provided a realistic hindcast of coral colony-scale (1-10 m) changing rugosity over the same period. We then projected future changes of Caribbean reef rugosity in response to global warming. Under severe and frequent thermal stress, the model predicted a dramatic loss of rugosity over the next two or three decades. Critically, reefs with managed parrotfish populations were able to delay the general loss of architectural complexity, as the benefits of grazing in maintaining living coral outweighed the bioerosion of dead coral skeletons. Overall, this model provides the first explicit projections of reef rugosity in a warming climate, and highlights the need of combining local (protecting and restoring high grazing) to global (mitigation of greenhouse gas emissions) interventions for the persistence of functional reef habitats. © 2014 John Wiley & Sons Ltd.

Working memory span in mild cognitive impairment. Influence of processing speed and cognitive reserve.

PubMed

Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina

2014-04-01

Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

NASA Astrophysics Data System (ADS)

Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

2007-02-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

Modeling Adaptable Business Service for Enterprise Collaboration

NASA Astrophysics Data System (ADS)

Boukadi, Khouloud; Vincent, Lucien; Burlat, Patrick

Nowadays, a Service Oriented Architecture (SOA) seems to be one of the most promising paradigms for leveraging enterprise information systems. SOA creates opportunities for enterprises to provide value added service tailored for on demand enterprise collaboration. With the emergence and rapid development of Web services technologies, SOA is being paid increasing attention and has become widespread. In spite of the popularity of SOA, a standardized framework for modeling and implementing business services are still in progress. For the purpose of supporting these service-oriented solutions, we adopt a model driven development approach. This paper outlines the Contextual Service Oriented Modeling and Analysis (CSOMA) methodology and presents UML profiles for the PIM level service-oriented architectural modeling, as well as its corresponding meta-models. The proposed PIM (Platform Independent Model) describes the business SOA at a high level of abstraction regardless of techniques involved in the application employment. In addition, all essential service-specific concerns required for delivering quality and context-aware service are covered. Some of the advantages of this approach are that it is generic and thus not closely allied with Web service technology as well as specifically treating the service adaptability during the design stage.

Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG.

PubMed

Asiltas, Burak; Surmen-Gur, Esma; Uncu, Gurkan

2018-02-27

Early diagnosis of preeclampsia (PE) is very important and various parameters, individually or in combined models, are reported useful for prediction of PE. The objective of this study is to investigate the predictive value of pregnancy-associated plasma protein-A (PAPP-A), placental protein-13 (PP-13), human Chorionic Gonadotropin (B-HCG), and oxidative stress marker malondialdehyde (MDA), individually and in combination. Maternal sera of 38 cases with PE and 122 controls were collected for first trimester screening and tested for PAPP-A and B-HCG by chemiluminescence, for PP-13 by using ELISA, and for MDA by high-performance liquid chromatography. Combined models of parameters were constituted as "MDA + PP-13", "PP-13 + PAPP-A + B-HCG" and "MDA + PP-13 + PAPP-A + B-HCG". The diagnostic performances of serum markers of preeclampsia were examined by nonparametric receiver-operator characteristics (ROC) analysis. PP-13 levels were significantly lower (p < 0.001) and MDA levels were significantly higher (p < 0.001) in PE. The area under the ROC curve (AUC) for MDA and PP-13 were greater than those for PAPP-A and B-HCG (p < 0.001). The AUCs of the combined models were significantly larger than those of individual parameters. The combined model "MDA + PP-13 + PAPP-A + B-HCG" exhibited the best predictive outcome with an AUC of 0.91 [95% CI 0.86-0.95], 97% [95% CI 86.2-99.9] sensitivity and 75% [95% CI 66.5-82.6] specificity, and was significantly different from that of "PAPP-A + PP-13 + B-HCG" model, but similar to that of "MDA + PP-13" model. Combined models consisting of various parameters of different origin, may provide better predictive outcomes, and oxidative markers should be considered in combination with other placental biomarkers in prediction of PE. Copyright © 2018 Elsevier B.V. All rights reserved.

[Effect of Electroacupuncture Intervention at Different Time-points on Levels of HSP 70, MDA, SOD and GSH-PX of Liver in Rats with Simulated Weightlessness].

PubMed

Song, Yan; Zhao, Guo-zhen; Zhao, Bai-xiao; Ji, Bo; Wang, De-sheng; Zhang, He; Mao, Ying-qiu; Zhang, Ping; Xu, Yong-si; Liu, Ya-li; Lu, Ya-wen; Dai, Jian; Li, Ying-hui

2015-10-01

To observe the effect of acupuncture intervention at different time-points on the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), the content of malonaldehyde (MDA) and expression of heat shock protein 70 (HSP 70) of liver tissue in rats with simulated weightlessness, so as to explore its mechanism underlying improvement of liver injury in rats with simulated weightlessness. Twenty male Wistar rats were randomly divided into control group, model group, pre-acupuncture group and EA group, 5 rats in each. The model of simulated weightlessness was established by tail suspension for 4 week. One week before the tail suspension, the rats in the pre-acupuncture group were treated with electroacupuncture (EA) at "Shenshu" (BL 23), "Pishu"(BL 20) and "Sanyinjiao" (SP 6) for 30 min before treatment, once a day for 7 days. The rats in the EA group received tail suspension and acupuncture intervention at the same time. EA was applied for 30 min per treatment, once every other day for 14 times. Immunohistochemical staining was used to assay the expression of HSP 70 in the liver tissue. The activities of SOD and GSH-PX and content of MDA in liver tissues were examined by means of colourimetric method. Results Compared with the control group,the expression of HSP 70 and the content of MDA in the liver tissue were increased significantly (P < 0.01), and the activity of SOD and GSH-PX was notably reduced (P < 0.05) in the model group. Compared with the model group, the content of HSP 70 was significantly reduced in the pre-acupuncture group (P < 0.01). There were no significant changes in the levels of SOD, GSH-PX, MDA and HSP 70 in the EA group (P > 0.05). In comparison with the pre-acupuncture group, the activity of GSH-PX was lower (P < 0.05) and the content of MDA was higher (P < 0.05) in the EA group. EA-pretreatment can suppress the increase of liver HSP 70 immunoactivity in rats with simulated weightlessness, being likely to improve the antioxidant ability of liver.

Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis.

PubMed

Moreno-Morcillo, María; Grande-García, Araceli; Ruiz-Ramos, Alba; Del Caño-Ochoa, Francisco; Boskovic, Jasminka; Ramón-Maiques, Santiago

2017-06-06

CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex.

PubMed

Onischenko, Evgeny; Tang, Jeffrey H; Andersen, Kasper R; Knockenhauer, Kevin E; Vallotton, Pascal; Derrer, Carina P; Kralt, Annemarie; Mugler, Christopher F; Chan, Leon Y; Schwartz, Thomas U; Weis, Karsten

2017-11-02

Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a new layer of connections to current models of the NPC architecture. Copyright © 2017 Elsevier Inc. All rights reserved.

End-to-end observatory software modeling using domain specific languages

NASA Astrophysics Data System (ADS)

Filgueira, José M.; Bec, Matthieu; Liu, Ning; Peng, Chien; Soto, José

2014-07-01

The Giant Magellan Telescope (GMT) is a 25-meter extremely large telescope that is being built by an international consortium of universities and research institutions. Its software and control system is being developed using a set of Domain Specific Languages (DSL) that supports a model driven development methodology integrated with an Agile management process. This approach promotes the use of standardized models that capture the component architecture of the system, that facilitate the construction of technical specifications in a uniform way, that facilitate communication between developers and domain experts and that provide a framework to ensure the successful integration of the software subsystems developed by the GMT partner institutions.

Evaluation of software maintain ability with open EHR - a comparison of architectures.

PubMed

Atalag, Koray; Yang, Hong Yul; Tempero, Ewan; Warren, James R

2014-11-01

To assess whether it is easier to maintain a clinical information system developed using open EHR model driven development versus mainstream methods. A new open source application (GastrOS) has been developed following open EHR's multi-level modelling approach using .Net/C# based on the same requirements of an existing clinically used application developed using Microsoft Visual Basic and Access database. Almost all the domain knowledge was embedded into the software code and data model in the latter. The same domain knowledge has been expressed as a set of open EHR Archetypes in GastrOS. We then introduced eight real-world change requests that had accumulated during live clinical usage, and implemented these in both systems while measuring time for various development tasks and change in software size for each change request. Overall it took half the time to implement changes in GastrOS. However it was the more difficult application to modify for one change request, suggesting the nature of change is also important. It was not possible to implement changes by modelling only. Comparison of relative measures of time and software size change within each application highlights how architectural differences affected maintain ability across change requests. The use of open EHR model driven development can result in better software maintain ability. The degree to which open EHR affects software maintain ability depends on the extent and nature of domain knowledge involved in changes. Although we used relative measures for time and software size, confounding factors could not be totally excluded as a controlled study design was not feasible. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Real-Time MENTAT programming language and architecture

NASA Technical Reports Server (NTRS)

Grimshaw, Andrew S.; Silberman, Ami; Liu, Jane W. S.

1989-01-01

Real-time MENTAT, a programming environment designed to simplify the task of programming real-time applications in distributed and parallel environments, is described. It is based on the same data-driven computation model and object-oriented programming paradigm as MENTAT. It provides an easy-to-use mechanism to exploit parallelism, language constructs for the expression and enforcement of timing constraints, and run-time support for scheduling and exciting real-time programs. The real-time MENTAT programming language is an extended C++. The extensions are added to facilitate automatic detection of data flow and generation of data flow graphs, to express the timing constraints of individual granules of computation, and to provide scheduling directives for the runtime system. A high-level view of the real-time MENTAT system architecture and programming language constructs is provided.

Using Real and Simulated TNOs to Constrain the Outer Solar System

NASA Astrophysics Data System (ADS)

Kaib, Nathan

2018-04-01

Over the past 2-3 decades our understanding of the outer solar system’s history and current state has evolved dramatically. An explosion in the number of detected trans-Neptunian objects (TNOs) coupled with simultaneous advances in numerical models of orbital dynamics has driven this rapid evolution. However, successfully constraining the orbital architecture and evolution of the outer solar system requires accurately comparing simulation results with observational datasets. This process is challenging because observed datasets are influenced by orbital discovery biases as well as TNO size and albedo distributions. Meanwhile, such influences are generally absent from numerical results. Here I will review recent work I and others have undertaken using numerical simulations in concert with catalogs of observed TNOs to constrain the outer solar system’s current orbital architecture and past evolution.

Failure analysis of woven and braided fabric reinforced composites

NASA Technical Reports Server (NTRS)

Naik, Rajiv A.

1994-01-01

A general purpose micromechanics analysis that discretely models the yarn architecture within the textile repeating unit cell was developed to predict overall, three dimensional, thermal and mechanical properties, damage initiation and progression, and strength. This analytical technique was implemented in a user-friendly, personal computer-based, menu-driven code called Textile Composite Analysis for Design (TEXCAD). TEXCAD was used to analyze plain weave and 2x2, 2-D triaxial braided composites. The calculated tension, compression, and shear strengths correlated well with available test data for both woven and braided composites. Parametric studies were performed on both woven and braided architectures to investigate the effects of parameters such as yarn size, yarn spacing, yarn crimp, braid angle, and overall fiber volume fraction on the strength properties of the textile composite.

The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.

PubMed Central

Colado, M. I.; Williams, J. L.; Green, A. R.

1995-01-01

1. The effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') and its N-demethylated product, 3,4-methylenedioxyamphetamine (MDA) on both rectal temperature and long term neurotoxic loss of cerebral 5-hydroxytryptamine (5-HT) has been studied in male and female Dark Agouti (DA) rats. The female metabolizes debrisoquine more slowly than the male and its use has been suggested as a model of the human debrisoquine 4-hydroxylase poor metabolizer phenotype. 2. A novel h.p.l.c. method was developed and used to measure plasma MDMA and MDA concentrations in the DA rats. 3. The hyperthermic response following MDMA was enhanced in female rats. Plasma MDMA concentrations were also 57% higher than in males 45 min post-injection, while plasma concentrations of MDA were 48% lower. 4. Plasma concentrations of MDMA and MDA in male rats were unaffected by pretreatment with proadifen (15 mg kg-1) or quinidine (60 mg kg-1), but the hyperthermic response to MDMA (10 mg kg-1, i.p.) was enhanced by quinidine pretreatment. 5. The hyperthermic response following MDA was greater in male DA rats, despite plasma drug concentrations being 40% higher in females 60 min after injection. 6. Seven days after a single dose of MDMA (10 mg kg-1, i.p.) there was a substantial loss in the concentration of 5-HT and 5-hydroxyindoleacetic acid (5-HIA) in cortex and hippocampus. [3H]-paroxetine binding was also decreased by 27% in the cortex, indicating that the amine loss reflected a neurodegenerative change. MDMA (5 mg kg-1, i.p.) was without effect on brain 5-HT content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582557

Mechanism of chimera formation during the Multiple Displacement Amplification reaction.

PubMed

Lasken, Roger S; Stockwell, Timothy B

2007-04-12

Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2-21 nucleotides (nts) in the new templates. Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

Mechanism of chimera formation during the Multiple Displacement Amplification reaction

PubMed Central

Lasken, Roger S; Stockwell, Timothy B

2007-01-01

Background Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts) in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications. PMID:17430586

Educational JavaBeans: a Requirements Driven Architecture.

ERIC Educational Resources Information Center

Hall, Jon; Rapanotti, Lucia

This paper investigates, through a case study, the development of a software architecture that is compatible with a system's high-level requirements. The case study is an example of an extended customer/supplier relationship (post-point of sale support) involved in e-universities and is representative of a class of enterprise without current…

A Socio-Cognitive Approach to Knowledge Construction in Design Studio through Blended Learning

ERIC Educational Resources Information Center

Kocaturk, Tuba

2017-01-01

This paper results from an educational research project that was undertaken by the School of Architecture, at the University of Liverpool funded by the Higher Education Academy in UK. The research explored technology driven shifts in architectural design studio education, identified their cognitive effects on design learning and developed an…

Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats.

PubMed

Khairy, Hanan; Saleh, Hanan; Badr, Abeer M; Marie, Mohamed-Assem S

2018-04-01

Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Molecularly Targeted Dose-Enhancement Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model

DTIC Science & Technology

2013-10-01

cell lines, such as cervix cancer cell line (HeLa) and breast cancer cell line (MDA-MB-231), were also employed. The experiments with other cell lines...breast cancer cell line (MDA-MB- 231), and cervix cancer cell line (HeLa). Different from our hypothesis, prostate cancer cell lines did not present...Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model PRINCIPAL INVESTIGATOR: Kwang Song

Reducing equifinality of hydrological models by integrating Functional Streamflow Disaggregation

NASA Astrophysics Data System (ADS)

Lüdtke, Stefan; Apel, Heiko; Nied, Manuela; Carl, Peter; Merz, Bruno

2014-05-01

A universal problem of the calibration of hydrological models is the equifinality of different parameter sets derived from the calibration of models against total runoff values. This is an intrinsic problem stemming from the quality of the calibration data and the simplified process representation by the model. However, discharge data contains additional information which can be extracted by signal processing methods. An analysis specifically developed for the disaggregation of runoff time series into flow components is the Functional Streamflow Disaggregation (FSD; Carl & Behrendt, 2008). This method is used in the calibration of an implementation of the hydrological model SWIM in a medium sized watershed in Thailand. FSD is applied to disaggregate the discharge time series into three flow components which are interpreted as base flow, inter-flow and surface runoff. In addition to total runoff, the model is calibrated against these three components in a modified GLUE analysis, with the aim to identify structural model deficiencies, assess the internal process representation and to tackle equifinality. We developed a model dependent (MDA) approach calibrating the model runoff components against the FSD components, and a model independent (MIA) approach comparing the FSD of the model results and the FSD of calibration data. The results indicate, that the decomposition provides valuable information for the calibration. Particularly MDA highlights and discards a number of standard GLUE behavioural models underestimating the contribution of soil water to river discharge. Both, MDA and MIA yield to a reduction of the parameter ranges by a factor up to 3 in comparison to standard GLUE. Based on these results, we conclude that the developed calibration approach is able to reduce the equifinality of hydrological model parameterizations. The effect on the uncertainty of the model predictions is strongest by applying MDA and shows only minor reductions for MIA. Besides further validation of FSD, the next steps include an extension of the study to different catchments and other hydrological models with a similar structure.

Fluid-driven origami-inspired artificial muscles.

PubMed

Li, Shuguang; Vogt, Daniel M; Rus, Daniela; Wood, Robert J

2017-12-12

Artificial muscles hold promise for safe and powerful actuation for myriad common machines and robots. However, the design, fabrication, and implementation of artificial muscles are often limited by their material costs, operating principle, scalability, and single-degree-of-freedom contractile actuation motions. Here we propose an architecture for fluid-driven origami-inspired artificial muscles. This concept requires only a compressible skeleton, a flexible skin, and a fluid medium. A mechanical model is developed to explain the interaction of the three components. A fabrication method is introduced to rapidly manufacture low-cost artificial muscles using various materials and at multiple scales. The artificial muscles can be programed to achieve multiaxial motions including contraction, bending, and torsion. These motions can be aggregated into systems with multiple degrees of freedom, which are able to produce controllable motions at different rates. Our artificial muscles can be driven by fluids at negative pressures (relative to ambient). This feature makes actuation safer than most other fluidic artificial muscles that operate with positive pressures. Experiments reveal that these muscles can contract over 90% of their initial lengths, generate stresses of ∼600 kPa, and produce peak power densities over 2 kW/kg-all equal to, or in excess of, natural muscle. This architecture for artificial muscles opens the door to rapid design and low-cost fabrication of actuation systems for numerous applications at multiple scales, ranging from miniature medical devices to wearable robotic exoskeletons to large deployable structures for space exploration. Copyright © 2017 the Author(s). Published by PNAS.

Fluid-driven origami-inspired artificial muscles

PubMed Central

Li, Shuguang; Vogt, Daniel M.; Rus, Daniela; Wood, Robert J.

2017-01-01

Artificial muscles hold promise for safe and powerful actuation for myriad common machines and robots. However, the design, fabrication, and implementation of artificial muscles are often limited by their material costs, operating principle, scalability, and single-degree-of-freedom contractile actuation motions. Here we propose an architecture for fluid-driven origami-inspired artificial muscles. This concept requires only a compressible skeleton, a flexible skin, and a fluid medium. A mechanical model is developed to explain the interaction of the three components. A fabrication method is introduced to rapidly manufacture low-cost artificial muscles using various materials and at multiple scales. The artificial muscles can be programed to achieve multiaxial motions including contraction, bending, and torsion. These motions can be aggregated into systems with multiple degrees of freedom, which are able to produce controllable motions at different rates. Our artificial muscles can be driven by fluids at negative pressures (relative to ambient). This feature makes actuation safer than most other fluidic artificial muscles that operate with positive pressures. Experiments reveal that these muscles can contract over 90% of their initial lengths, generate stresses of ∼600 kPa, and produce peak power densities over 2 kW/kg—all equal to, or in excess of, natural muscle. This architecture for artificial muscles opens the door to rapid design and low-cost fabrication of actuation systems for numerous applications at multiple scales, ranging from miniature medical devices to wearable robotic exoskeletons to large deployable structures for space exploration. PMID:29180416

Fluid-driven origami-inspired artificial muscles

NASA Astrophysics Data System (ADS)

Li, Shuguang; Vogt, Daniel M.; Rus, Daniela; Wood, Robert J.

2017-12-01

Artificial muscles hold promise for safe and powerful actuation for myriad common machines and robots. However, the design, fabrication, and implementation of artificial muscles are often limited by their material costs, operating principle, scalability, and single-degree-of-freedom contractile actuation motions. Here we propose an architecture for fluid-driven origami-inspired artificial muscles. This concept requires only a compressible skeleton, a flexible skin, and a fluid medium. A mechanical model is developed to explain the interaction of the three components. A fabrication method is introduced to rapidly manufacture low-cost artificial muscles using various materials and at multiple scales. The artificial muscles can be programed to achieve multiaxial motions including contraction, bending, and torsion. These motions can be aggregated into systems with multiple degrees of freedom, which are able to produce controllable motions at different rates. Our artificial muscles can be driven by fluids at negative pressures (relative to ambient). This feature makes actuation safer than most other fluidic artificial muscles that operate with positive pressures. Experiments reveal that these muscles can contract over 90% of their initial lengths, generate stresses of ˜600 kPa, and produce peak power densities over 2 kW/kg—all equal to, or in excess of, natural muscle. This architecture for artificial muscles opens the door to rapid design and low-cost fabrication of actuation systems for numerous applications at multiple scales, ranging from miniature medical devices to wearable robotic exoskeletons to large deployable structures for space exploration.

Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion.

PubMed

Larsson, Karin; Harrysson, Hanna; Havenaar, Robert; Alminger, Marie; Undeland, Ingrid

2016-02-01

Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ∼ 25 μM MDA and ∼ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ≫ herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids.

Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein.

PubMed Central

Requena, J R; Fu, M X; Ahmed, M U; Jenkins, A J; Lyons, T J; Baynes, J W; Thorpe, S R

1997-01-01

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(N epsilon-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(N epsilon-lysino)propane (LML)] and lysine-HNE [3-(N epsilon-lysino)-4-hydroxynonan-l-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70-80% of total lysine loss during the reaction with MDA. LM and LML (0.002-0.12 mmol/ mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo. PMID:9078279

EVA/ORU model architecture using RAMCOST

NASA Technical Reports Server (NTRS)

Ntuen, Celestine A.; Park, Eui H.; Wang, Y. M.; Bretoi, R.

1990-01-01

A parametrically driven simulation model is presented in order to provide a detailed insight into the effects of various input parameters in the life testing of a modular space suit. The RAMCOST model employed is a user-oriented simulation model for studying the life-cycle costs of designs under conditions of uncertainty. The results obtained from the EVA simulated model are used to assess various mission life testing parameters such as the number of joint motions per EVA cycle time, part availability, and number of inspection requirements. RAMCOST first simulates EVA completion for NASA application using a probabilistic like PERT network. With the mission time heuristically determined, RAMCOST then models different orbital replacement unit policies with special application to the astronaut's space suit functional designs.

A Roadmap for caGrid, an Enterprise Grid Architecture for Biomedical Research

PubMed Central

Saltz, Joel; Hastings, Shannon; Langella, Stephen; Oster, Scott; Kurc, Tahsin; Payne, Philip; Ferreira, Renato; Plale, Beth; Goble, Carole; Ervin, David; Sharma, Ashish; Pan, Tony; Permar, Justin; Brezany, Peter; Siebenlist, Frank; Madduri, Ravi; Foster, Ian; Shanbhag, Krishnakant; Mead, Charlie; Hong, Neil Chue

2012-01-01

caGrid is a middleware system which combines the Grid computing, the service oriented architecture, and the model driven architecture paradigms to support development of interoperable data and analytical resources and federation of such resources in a Grid environment. The functionality provided by caGrid is an essential and integral component of the cancer Biomedical Informatics Grid (caBIG™) program. This program is established by the National Cancer Institute as a nationwide effort to develop enabling informatics technologies for collaborative, multi-institutional biomedical research with the overarching goal of accelerating translational cancer research. Although the main application domain for caGrid is cancer research, the infrastructure provides a generic framework that can be employed in other biomedical research and healthcare domains. The development of caGrid is an ongoing effort, adding new functionality and improvements based on feedback and use cases from the community. This paper provides an overview of potential future architecture and tooling directions and areas of improvement for caGrid and caGrid-like systems. This summary is based on discussions at a roadmap workshop held in February with participants from biomedical research, Grid computing, and high performance computing communities. PMID:18560123

A roadmap for caGrid, an enterprise Grid architecture for biomedical research.

PubMed

Saltz, Joel; Hastings, Shannon; Langella, Stephen; Oster, Scott; Kurc, Tahsin; Payne, Philip; Ferreira, Renato; Plale, Beth; Goble, Carole; Ervin, David; Sharma, Ashish; Pan, Tony; Permar, Justin; Brezany, Peter; Siebenlist, Frank; Madduri, Ravi; Foster, Ian; Shanbhag, Krishnakant; Mead, Charlie; Chue Hong, Neil

2008-01-01

caGrid is a middleware system which combines the Grid computing, the service oriented architecture, and the model driven architecture paradigms to support development of interoperable data and analytical resources and federation of such resources in a Grid environment. The functionality provided by caGrid is an essential and integral component of the cancer Biomedical Informatics Grid (caBIG) program. This program is established by the National Cancer Institute as a nationwide effort to develop enabling informatics technologies for collaborative, multi-institutional biomedical research with the overarching goal of accelerating translational cancer research. Although the main application domain for caGrid is cancer research, the infrastructure provides a generic framework that can be employed in other biomedical research and healthcare domains. The development of caGrid is an ongoing effort, adding new functionality and improvements based on feedback and use cases from the community. This paper provides an overview of potential future architecture and tooling directions and areas of improvement for caGrid and caGrid-like systems. This summary is based on discussions at a roadmap workshop held in February with participants from biomedical research, Grid computing, and high performance computing communities.

Linking and Combining Distributed Operations Facilities using NASA's "GMSEC" Systems Architectures

NASA Technical Reports Server (NTRS)

Smith, Danford; Grubb, Thomas; Esper, Jaime

2008-01-01

NASA's Goddard Mission Services Evolution Center (GMSEC) ground system architecture has been in development since late 2001, has successfully supported eight orbiting satellites and is being applied to many of NASA's future missions. GMSEC can be considered an event-driven service-oriented architecture built around a publish/subscribe message bus middleware. This paper briefly discusses the GMSEC technical approaches which have led to significant cost savings and risk reduction for NASA missions operated at the Goddard Space Flight Center (GSFC). The paper then focuses on the development and operational impacts of extending the architecture across multiple mission operations facilities.

Enabling Data-Driven Methodologies Across the Data Lifecycle and Ecosystem

NASA Astrophysics Data System (ADS)

Doyle, R. J.; Crichton, D.

2017-12-01

NASA has unlocked unprecedented scientific knowledge through exploration of the Earth, our solar system, and the larger universe. NASA is generating enormous amounts of data that are challenging traditional approaches to capturing, managing, analyzing and ultimately gaining scientific understanding from science data. New architectures, capabilities and methodologies are needed to span the entire observing system, from spacecraft to archive, while integrating data-driven discovery and analytic capabilities. NASA data have a definable lifecycle, from remote collection point to validated accessibility in multiple archives. Data challenges must be addressed across this lifecycle, to capture opportunities and avoid decisions that may limit or compromise what is achievable once data arrives at the archive. Data triage may be necessary when the collection capacity of the sensor or instrument overwhelms data transport or storage capacity. By migrating computational and analytic capability to the point of data collection, informed decisions can be made about which data to keep; in some cases, to close observational decision loops onboard, to enable attending to unexpected or transient phenomena. Along a different dimension than the data lifecycle, scientists and other end-users must work across an increasingly complex data ecosystem, where the range of relevant data is rarely owned by a single institution. To operate effectively, scalable data architectures and community-owned information models become essential. NASA's Planetary Data System is having success with this approach. Finally, there is the difficult challenge of reproducibility and trust. While data provenance techniques will be part of the solution, future interactive analytics environments must support an ability to provide a basis for a result: relevant data source and algorithms, uncertainty tracking, etc., to assure scientific integrity and to enable confident decision making. Advances in data science offer opportunities to gain new insights from space missions and their vast data collections. We are working to innovate new architectures, exploit emerging technologies, develop new data-driven methodologies, and transfer them across disciplines, while working across the dual dimensions of the data lifecycle and the data ecosystem.

Impact of wildfires on ozone exceptional events in the Western u.s.

PubMed

Jaffe, Daniel A; Wigder, Nicole; Downey, Nicole; Pfister, Gabriele; Boynard, Anne; Reid, Stephen B

2013-10-01

Wildfires generate substantial emissions of nitrogen oxides (NOx) and volatile organic compounds (VOCs). As such, wildfires contribute to elevated ozone (O3) in the atmosphere. However, there is a large amount of variability in the emissions of O3 precursors and the amount of O3 produced between fires. There is also significant interannual variability as seen in median O3, organic carbon and satellite derived carbon monoxide mixing ratios in the western U.S. To better understand O3 produced from wildfires, we developed a statistical model that estimates the maximum daily 8 h average (MDA8) O3 as a function of several meteorological and temporal variables for three urban areas in the western U.S.: Salt Lake City, UT; Boise, ID; and Reno, NV. The model is developed using data from June-September 2000-2012. For these three locations, the statistical model can explain 60, 52, and 27% of the variability in daily MDA8. The Statistical Model Residual (SMR) can give information on additional sources of O3 that are not explained by the usual meteorological pattern. Several possible O3 sources can explain high SMR values on any given day. We examine several cases with high SMR that are due to wildfire influence. The first case considered is for Reno in June 2008 when the MDA8 reached 82 ppbv. The wildfire influence for this episode is supported by PM concentrations, the known location of wildfires at the time and simulations with the Weather and Research Forecasting Model with Chemistry (WRF-Chem) which indicates transport to Reno from large fires burning in California. The contribution to the MDA8 in Reno from the California wildfires is estimated to be 26 ppbv, based on the SMR, and 60 ppbv, based on WRF-Chem. The WRF-Chem model also indicates an important role for peroxyacetyl nitrate (PAN) in producing O3 during transport from the California wildfires. We hypothesize that enhancements in PAN due to wildfire emissions may lead to regional enhancements in O3 during high fire years. The second case is for the Salt Lake City (SLC) region for August 2012. During this period the MDA8 reached 83 ppbv and the SMR suggests a wildfire contribution of 19 ppbv to the MDA8. The wildfire influence is supported by PM2.5 data, the known location of wildfires at the time, HYSPLIT dispersion modeling that indicates transport from fires in Idaho, and results from the CMAQ model that confirm the fire impacts. Concentrations of PM2.5 and O3 are enhanced during this period, but overall there is a poor relationship between them, which is consistent with the complexities in the secondary production of O3. A third case looks at high MDA8 in Boise, ID, during July 2012 and reaches similar conclusions. These results support the use of statistical modeling as a tool to quantify the influence from wildfires on urban O3 concentrations.

SATware: A Semantic Approach for Building Sentient Spaces

NASA Astrophysics Data System (ADS)

Massaguer, Daniel; Mehrotra, Sharad; Vaisenberg, Ronen; Venkatasubramanian, Nalini

This chapter describes the architecture of a semantic-based middleware environment for building sensor-driven sentient spaces. The proposed middleware explicitly models sentient space semantics (i.e., entities, spaces, activities) and supports mechanisms to map sensor observations to the state of the sentient space. We argue how such a semantic approach provides a powerful programming environment for building sensor spaces. In addition, the approach provides natural ways to exploit semantics for variety of purposes including scheduling under resource constraints and sensor recalibration.

Evaluation of the antioxidant impact of ginger-based kombucha on the murine breast cancer model.

PubMed

Salafzoon, Samaneh; Mahmoodzadeh Hosseini, Hamideh; Halabian, Raheleh

2017-10-21

Background Abnormal metabolism is a common event in cancerous cells. For example, the increase of reactive oxygen species (ROS) production, particularly due to aerobic respiration during invasive stage, results in cancer progression. Herein, the impact of kombucha tea prepared from ginger on the alteration of antioxidant agents was assessed in the breast cancer animal model. Methods Two types of kombucha tea with or without ginger were administered to BALB/c mice before and after tumor challenge. Superoxide dismutase (SOD), catalase, glutathione (GSH) and malondialdehyde (MDA) were evaluated in tumor, liver and kidney. Results Administration of kombucha ginger tea significantly decreased catalase activity as well as GSH and MDA level in tumor homogenate (p<0.001). A significant decrease in SOD activity and increase in MDA quantity was determined in the kidney which had received kombucha ginger tea (p<0.01). Conclusions The consumption of kombucha prepared from ginger could exert minor antioxidant impacts by balancing multi antioxidant factors in different tissues in the breast cancer models.

Mapping and modelling the impact of mass drug adminstration on filariasis prevalence in Myanmar.

PubMed

Aye, Ni Ni; Lin, Zaw; Lon, Khin Nan; Linn, Nay Yi Yi; Nwe, Thet Wai; Mon, Khin Mon; Ramaiah, Kapa; Betts, Hannah; Kelly-Hope, Louise A

2018-05-31

Lymphatic filariasis (LF) is endemic in Myanmar and targeted for elimination. To highlight the National Programme to Eliminate Lymphatic Filariasis (NPELF) progress between 2000 and 2014, this paper describes the geographical distribution of LF, the scale-up and impact of mass drug administration (MDA) implementation, and the first evidence of the decline in transmission in five districts. The LF distribution was determined by mapping historical and baseline prevalence data collected by NPELF. Data on the MDA implementation, reported coverage rates and sentinel site surveillance were summarized. A statistical model was developed from the available prevalence data to predict prevalence at township level by year of measurement. Transmission assessment survey (TAS) methods, measuring antigenemia (Ag) prevalence in children, were used to determine whether prevalence was below a level where recrudescence is unlikely to occur. The highest baseline LF prevalence was found in the Central Valley region. The MDA implementation activities scaled up to cover 45 districts, representing the majority of the endemic population, with drug coverage rates ranging from 60.0% to 98.5%. Challenges related to drug supply and local conflict were reported, and interrupted MDA in some districts. Overall, significant reductions in LF prevalence were found, especially after the first 2 to 3 rounds of MDA, which was supported by the corresponding model. The TAS activities in five districts found only two Ag positive children, resulting in all districts passing the critical threshold. Overall, the Myanmar NPELF has made positive steps forward in the elimination of LF despite several challenges, however, it needs to maintain momentum, drawing on international stakeholder support, to aim towards the national and global goals of elimination.

A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

NASA Astrophysics Data System (ADS)

Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

2015-03-01

In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

Compiler-Driven Performance Optimization and Tuning for Multicore Architectures

DTIC Science & Technology

2015-04-10

develop a powerful system for auto-tuning of library routines and compute-intensive kernels, driven by the Pluto system for multicores that we are...kernels, driven by the Pluto system for multicores that we are developing. The work here is motivated by recent advances in two major areas of...automatic C-to-CUDA code generator using a polyhedral compiler transformation framework. We have used and adapted PLUTO (our state-of-the-art tool

The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

PubMed

Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

2017-05-23

Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline prevalence alone is not sufficient to inform policy for the control of STH, post cessation of LF MDA, since this will be highly dependent on the intensity and effectiveness of past programmes and the intrinsic transmission intensity of the dominant STH species in any given setting.

Implementing a Dynamic Database-Driven Course Using LAMP

ERIC Educational Resources Information Center

Laverty, Joseph Packy; Wood, David; Turchek, John

2011-01-01

This paper documents the formulation of a database driven open source architecture web development course. The design of a web-based curriculum faces many challenges: a) relative emphasis of client and server-side technologies, b) choice of a server-side language, and c) the cost and efficient delivery of a dynamic web development, database-driven…

Advantages of Brahms for Specifying and Implementing a Multiagent Human-Robotic Exploration System

NASA Technical Reports Server (NTRS)

Clancey, William J.; Sierhuis, Maarten; Kaskiris, Charis; vanHoof, Ron

2003-01-01

We have developed a model-based, distributed architecture that integrates diverse components in a system designed for lunar and planetary surface operations: an astronaut's space suit, cameras, all-terrain vehicles, robotic assistant, crew in a local habitat, and mission support team. Software processes ('agents') implemented in the Brahms language, run on multiple, mobile platforms. These mobile agents interpret and transform available data to help people and robotic systems coordinate their actions to make operations more safe and efficient. The Brahms-based mobile agent architecture (MAA) uses a novel combination of agent types so the software agents may understand and facilitate communications between people and between system components. A state-of-the-art spoken dialogue interface is integrated with Brahms models, supporting a speech-driven field observation record and rover command system. An important aspect of the methodology involves first simulating the entire system in Brahms, then configuring the agents into a runtime system Thus, Brahms provides a language, engine, and system builder's toolkit for specifying and implementing multiagent systems.

High efficiency cabin air filter in vehicles reduces drivers' roadway particulate matter exposures and associated lipid peroxidation

PubMed Central

Shu, Shi; Lin, Yan; She, Jianwen; Ip, Ho Sai Simon; Qiu, Xinghua; Zhu, Yifang

2017-01-01

Commuters who spend long hours on roads are exposed to high levels of traffic related air pollutants (TRAPs). Despite some well-known multiple adverse effects of TRAPs on human health, limited studies have focused on mitigation strategies to reduce these effects. In this study, we measured fine particulate matter (PM2.5) and ultrafine particle (UFP) concentrations inside and outside 17 taxis simultaneously while they were driven on roadways. The drivers’ urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and malondialdehyde (MDA) concentrations just before and right after the driving tests were also determined. Data were collected under three driving conditions (i.e. no mitigation (NM), window closed (WC), and window closed plus using high efficiency cabin air filters (WC+HECA)) for each taxi and driver. The results show that, compared to NM, the WC+HECA reduced in-cabin PM2.5 and UFP concentrations, by 37% and 47% respectively (p < 0.05), whereas the reductions on PAH exposures were insignificant. Although nonsignificant, a reduction of 17% was also observed in the drivers’ urinary MDA under WC+HECA. The MDA concentrations were found to be significantly associated with the in-cabin PM2.5 and UFP concentrations, suggesting the reduction of the drivers’ lipid peroxidation can be at least partially attributed to the PM2.5 and UFP reduction by WC+HECA. Overall, these results suggest HECA filters have potential to reduce particle levels inside taxis and protect drivers’ health. PMID:29176859

High efficiency cabin air filter in vehicles reduces drivers' roadway particulate matter exposures and associated lipid peroxidation.

PubMed

Yu, Nu; Shu, Shi; Lin, Yan; She, Jianwen; Ip, Ho Sai Simon; Qiu, Xinghua; Zhu, Yifang

2017-01-01

Commuters who spend long hours on roads are exposed to high levels of traffic related air pollutants (TRAPs). Despite some well-known multiple adverse effects of TRAPs on human health, limited studies have focused on mitigation strategies to reduce these effects. In this study, we measured fine particulate matter (PM2.5) and ultrafine particle (UFP) concentrations inside and outside 17 taxis simultaneously while they were driven on roadways. The drivers' urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and malondialdehyde (MDA) concentrations just before and right after the driving tests were also determined. Data were collected under three driving conditions (i.e. no mitigation (NM), window closed (WC), and window closed plus using high efficiency cabin air filters (WC+HECA)) for each taxi and driver. The results show that, compared to NM, the WC+HECA reduced in-cabin PM2.5 and UFP concentrations, by 37% and 47% respectively (p < 0.05), whereas the reductions on PAH exposures were insignificant. Although nonsignificant, a reduction of 17% was also observed in the drivers' urinary MDA under WC+HECA. The MDA concentrations were found to be significantly associated with the in-cabin PM2.5 and UFP concentrations, suggesting the reduction of the drivers' lipid peroxidation can be at least partially attributed to the PM2.5 and UFP reduction by WC+HECA. Overall, these results suggest HECA filters have potential to reduce particle levels inside taxis and protect drivers' health.

Seasonally timed treatment programs for Ascaris lumbricoides to increase impact—An investigation using mathematical models

PubMed Central

Danon, Leon; Prada, Joaquín M.; Gunawardena, Sharmini A.; Truscott, James E.; Vlaminck, Johnny; Anderson, Roy M.; Levecke, Bruno; Morgan, Eric R; Hollingsworth, T. Deirdre

2018-01-01

There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings. PMID:29346383

Integrated Array/Metadata Analytics

NASA Astrophysics Data System (ADS)

Misev, Dimitar; Baumann, Peter

2015-04-01

Data comes in various forms and types, and integration usually presents a problem that is often simply ignored and solved with ad-hoc solutions. Multidimensional arrays are an ubiquitous data type, that we find at the core of virtually all science and engineering domains, as sensor, model, image, statistics data. Naturally, arrays are richly described by and intertwined with additional metadata (alphanumeric relational data, XML, JSON, etc). Database systems, however, a fundamental building block of what we call "Big Data", lack adequate support for modelling and expressing these array data/metadata relationships. Array analytics is hence quite primitive or non-existent at all in modern relational DBMS. Recognizing this, we extended SQL with a new SQL/MDA part seamlessly integrating multidimensional array analytics into the standard database query language. We demonstrate the benefits of SQL/MDA with real-world examples executed in ASQLDB, an open-source mediator system based on HSQLDB and rasdaman, that already implements SQL/MDA.

LDRD project final report : hybrid AI/cognitive tactical behavior framework for LVC.

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

Djordjevich, Donna D.; Xavier, Patrick Gordon; Brannon, Nathan Gregory

This Lab-Directed Research and Development (LDRD) sought to develop technology that enhances scenario construction speed, entity behavior robustness, and scalability in Live-Virtual-Constructive (LVC) simulation. We investigated issues in both simulation architecture and behavior modeling. We developed path-planning technology that improves the ability to express intent in the planning task while still permitting an efficient search algorithm. An LVC simulation demonstrated how this enables 'one-click' layout of squad tactical paths, as well as dynamic re-planning for simulated squads and for real and simulated mobile robots. We identified human response latencies that can be exploited in parallel/distributed architectures. We did an experimentalmore » study to determine where parallelization would be productive in Umbra-based force-on-force (FOF) simulations. We developed and implemented a data-driven simulation composition approach that solves entity class hierarchy issues and supports assurance of simulation fairness. Finally, we proposed a flexible framework to enable integration of multiple behavior modeling components that model working memory phenomena with different degrees of sophistication.« less

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

Knirsch, Fabian; Engel, Dominik; Neureiter, Christian

In a smart grid, data and information are transported, transmitted, stored, and processed with various stakeholders having to cooperate effectively. Furthermore, personal data is the key to many smart grid applications and therefore privacy impacts have to be taken into account. For an effective smart grid, well integrated solutions are crucial and for achieving a high degree of customer acceptance, privacy should already be considered at design time of the system. To assist system engineers in early design phase, frameworks for the automated privacy evaluation of use cases are important. For evaluation, use cases for services and software architectures needmore » to be formally captured in a standardized and commonly understood manner. In order to ensure this common understanding for all kinds of stakeholders, reference models have recently been developed. In this paper we present a model-driven approach for the automated assessment of such services and software architectures in the smart grid that builds on the standardized reference models. The focus of qualitative and quantitative evaluation is on privacy. For evaluation, the framework draws on use cases from the University of Southern California microgrid.« less

Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease.

PubMed

Lapolla, Annunziata; Piarulli, Francesco; Sartore, Giovanni; Ceriello, Antonio; Ragazzi, Eugenio; Reitano, Rachele; Baccarin, Lorenzo; Laverda, Barbara; Fedele, Domenico

2007-03-01

Advanced glycation end products (AGEs), pentosidine and malondialdehyde (MDA), are elevated in type 2 diabetic subjects with coronary and carotid angiopathy. We investigated the relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD). AGEs, pentosidine, MDA, TRAP, vitamin E, and ankle-brachial index (ABI) were measured in 99 consecutive type 2 diabetic subjects and 20 control subjects. AGEs, pentosidine, and MDA were higher and vitamin E and TRAP were lower in patients with PAD (ABI <0.9) than in patients without PAD (ABI >0.9) (P < 0.001). After multiple regression analysis, a correlation between AGEs and pentosidine, as independent variables, and ABI, as the dependent variable, was found in both patients with and without PAD (r = 0.9198, P < 0.001 and r = 0.5764, P < 0.001, respectively) but not in control subjects. When individual regression coefficients were evaluated, only that due to pentosidine was confirmed as significant. For patients with PAD, considering TRAP, vitamin E, and MDA as independent variables and ABI as the dependent variable produced an overall significant regression (r = 0.6913, P < 0.001). The regression coefficients for TRAP and vitamin E were not significant, indicating that the model is best explained by a single linear regression between MDA and ABI. These findings were also confirmed by principal component analysis. Results show that pentosidine and MDA are strongly associated with PAD in type 2 diabetic patients.

Climate, weather, space weather: model development in an operational context

NASA Astrophysics Data System (ADS)

Folini, Doris

2018-05-01

Aspects of operational modeling for climate, weather, and space weather forecasts are contrasted, with a particular focus on the somewhat conflicting demands of "operational stability" versus "dynamic development" of the involved models. Some common key elements are identified, indicating potential for fruitful exchange across communities. Operational model development is compelling, driven by factors that broadly fall into four categories: model skill, basic physics, advances in computer architecture, and new aspects to be covered, from costumer needs over physics to observational data. Evaluation of model skill as part of the operational chain goes beyond an automated skill score. Permanent interaction between "pure research" and "operational forecast" people is beneficial to both sides. This includes joint model development projects, although ultimate responsibility for the operational code remains with the forecast provider. The pace of model development reflects operational lead times. The points are illustrated with selected examples, many of which reflect the author's background and personal contacts, notably with the Swiss Weather Service and the Max Planck Institute for Meteorology, Hamburg, Germany. In view of current and future challenges, large collaborations covering a range of expertise are a must - within and across climate, weather, and space weather. To profit from and cope with the rapid progress of computer architectures, supercompute centers must form part of the team.

The PDS4 Information Model and its Role in Agile Science Data Curation

NASA Astrophysics Data System (ADS)

Hughes, J. S.; Crichton, D.

2017-12-01

PDS4 is an information model-driven service architecture supporting the capture, management, distribution and integration of massive planetary science data captured in distributed data archives world-wide. The PDS4 Information Model (IM), the core element of the architecture, was developed using lessons learned from 20 years of archiving Planetary Science Data and best practices for information model development. The foundational principles were adopted from the Open Archival Information System (OAIS) Reference Model (ISO 14721), the Metadata Registry Specification (ISO/IEC 11179), and W3C XML (Extensible Markup Language) specifications. These provided respectively an object oriented model for archive information systems, a comprehensive schema for data dictionaries and hierarchical governance, and rules for rules for encoding documents electronically. The PDS4 Information model is unique in that it drives the PDS4 infrastructure by providing the representation of concepts and their relationships, constraints, rules, and operations; a sharable, stable, and organized set of information requirements; and machine parsable definitions that are suitable for configuring and generating code. This presentation will provide an over of the PDS4 Information Model and how it is being leveraged to develop and evolve the PDS4 infrastructure and enable agile curation of over 30 years of science data collected by the international Planetary Science community.

Dissecting the role of Engrailed in adult dopaminergic neurons--Insights into Parkinson disease pathogenesis.

PubMed

Rekaik, Hocine; Blaudin de Thé, François-Xavier; Prochiantz, Alain; Fuchs, Julia; Joshi, Rajiv L

2015-12-21

The homeoprotein Engrailed (Engrailed-1/Engrailed-2, collectively En1/2) is not only a survival factor for mesencephalic dopaminergic (mDA) neurons during development, but continues to exert neuroprotective and physiological functions in adult mDA neurons. Loss of one En1 allele in the mouse leads to progressive demise of mDA neurons in the ventral midbrain starting from 6 weeks of age. These mice also develop Parkinson disease-like motor and non-motor symptoms. The characterization of En1 heterozygous mice have revealed striking parallels to central mechanisms of Parkinson disease pathogenesis, mainly related to mitochondrial dysfunction and retrograde degeneration. Thanks to the ability of homeoproteins to transduce cells, En1/2 proteins have also been used to protect mDA neurons in various experimental models of Parkinson disease. This neuroprotection is partly linked to the ability of En1/2 to regulate the translation of certain nuclear-encoded mitochondrial mRNAs for complex I subunits. Other transcription factors that govern mDA neuron development (e.g. Foxa1/2, Lmx1a/b, Nurr1, Otx2, Pitx3) also continue to function for the survival and maintenance of mDA neurons in the adult and act through partially overlapping but also diverse mechanisms. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Cooperating reduction machines

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

Kluge, W.E.

1983-11-01

This paper presents a concept and a system architecture for the concurrent execution of program expressions of a concrete reduction language based on lamda-expressions. If formulated appropriately, these expressions are well-suited for concurrent execution, following a demand-driven model of computation. In particular, recursive program expressions with nonlinear expansion may, at run time, recursively be partitioned into a hierarchy of independent subexpressions which can be reduced by a corresponding hierarchy of virtual reduction machines. This hierarchy unfolds and collapses dynamically, with virtual machines recursively assuming the role of masters that create and eventually terminate, or synchronize with, slaves. The paper alsomore » proposes a nonhierarchically organized system of reduction machines, each featuring a stack architecture, that effectively supports the allocation of virtual machines to the real machines of the system in compliance with their hierarchical order of creation and termination. 25 references.« less

Localization Framework for Real-Time UAV Autonomous Landing: An On-Ground Deployed Visual Approach

PubMed Central

Kong, Weiwei; Hu, Tianjiang; Zhang, Daibing; Shen, Lincheng; Zhang, Jianwei

2017-01-01

One of the greatest challenges for fixed-wing unmanned aircraft vehicles (UAVs) is safe landing. Hereafter, an on-ground deployed visual approach is developed in this paper. This approach is definitely suitable for landing within the global navigation satellite system (GNSS)-denied environments. As for applications, the deployed guidance system makes full use of the ground computing resource and feedbacks the aircraft’s real-time localization to its on-board autopilot. Under such circumstances, a separate long baseline stereo architecture is proposed to possess an extendable baseline and wide-angle field of view (FOV) against the traditional fixed baseline schemes. Furthermore, accuracy evaluation of the new type of architecture is conducted by theoretical modeling and computational analysis. Dataset-driven experimental results demonstrate the feasibility and effectiveness of the developed approach. PMID:28629189

Localization Framework for Real-Time UAV Autonomous Landing: An On-Ground Deployed Visual Approach.

PubMed

Kong, Weiwei; Hu, Tianjiang; Zhang, Daibing; Shen, Lincheng; Zhang, Jianwei

2017-06-19

[-5]One of the greatest challenges for fixed-wing unmanned aircraft vehicles (UAVs) is safe landing. Hereafter, an on-ground deployed visual approach is developed in this paper. This approach is definitely suitable for landing within the global navigation satellite system (GNSS)-denied environments. As for applications, the deployed guidance system makes full use of the ground computing resource and feedbacks the aircraft's real-time localization to its on-board autopilot. Under such circumstances, a separate long baseline stereo architecture is proposed to possess an extendable baseline and wide-angle field of view (FOV) against the traditional fixed baseline schemes. Furthermore, accuracy evaluation of the new type of architecture is conducted by theoretical modeling and computational analysis. Dataset-driven experimental results demonstrate the feasibility and effectiveness of the developed approach.

Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

PubMed

McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

2016-07-01

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. ©2016 American Association for Cancer Research.

HOTS: A Hierarchy of Event-Based Time-Surfaces for Pattern Recognition.

PubMed

Lagorce, Xavier; Orchard, Garrick; Galluppi, Francesco; Shi, Bertram E; Benosman, Ryad B

2017-07-01

This paper describes novel event-based spatio-temporal features called time-surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy.This paper describes novel event-based spatio-temporal features called time-surfaces and how they can be used to create a hierarchical event-based pattern recognition architecture. Unlike existing hierarchical architectures for pattern recognition, the presented model relies on a time oriented approach to extract spatio-temporal features from the asynchronously acquired dynamics of a visual scene. These dynamics are acquired using biologically inspired frameless asynchronous event-driven vision sensors. Similarly to cortical structures, subsequent layers in our hierarchy extract increasingly abstract features using increasingly large spatio-temporal windows. The central concept is to use the rich temporal information provided by events to create contexts in the form of time-surfaces which represent the recent temporal activity within a local spatial neighborhood. We demonstrate that this concept can robustly be used at all stages of an event-based hierarchical model. First layer feature units operate on groups of pixels, while subsequent layer feature units operate on the output of lower level feature units. We report results on a previously published 36 class character recognition task and a four class canonical dynamic card pip task, achieving near 100 percent accuracy on each. We introduce a new seven class moving face recognition task, achieving 79 percent accuracy.

A computer architecture for intelligent machines

NASA Technical Reports Server (NTRS)

Lefebvre, D. R.; Saridis, G. N.

1992-01-01

The theory of intelligent machines proposes a hierarchical organization for the functions of an autonomous robot based on the principle of increasing precision with decreasing intelligence. An analytic formulation of this theory using information-theoretic measures of uncertainty for each level of the intelligent machine has been developed. The authors present a computer architecture that implements the lower two levels of the intelligent machine. The architecture supports an event-driven programming paradigm that is independent of the underlying computer architecture and operating system. Execution-level controllers for motion and vision systems are briefly addressed, as well as the Petri net transducer software used to implement coordination-level functions. A case study illustrates how this computer architecture integrates real-time and higher-level control of manipulator and vision systems.

Architecture-driven reuse of code in KASE

NASA Technical Reports Server (NTRS)

Bhansali, Sanjay

1993-01-01

In order to support the synthesis of large, complex software systems, we need to focus on issues pertaining to the architectural design of a system in addition to algorithm and data structure design. An approach that is based on abstracting the architectural design of a set of problems in the form of a generic architecture, and providing tools that can be used to instantiate the generic architecture for specific problem instances is presented. Such an approach also facilitates reuse of code between different systems belonging to the same problem class. An application of our approach on a realistic problem is described; the results of the exercise are presented; and how our approach compares to other work in this area is discussed.

Decision Aids Using Heterogeneous Intelligence Analysis

DTIC Science & Technology

2010-08-20

developing a Geocultural service, a software framework and inferencing engine for the Transparent Urban Structures program. The scope of the effort...has evolved as the program has matured and is including multiple data sources, as well as interfaces out to the ONR architectural framework . Tasks...Interface; Application Program Interface; Application Programmer Interface CAF Common Application Framework EDA Event Driven Architecture a 16. SECURITY

Optical, analog and digital domain architectural considerations for visual communications

NASA Astrophysics Data System (ADS)

Metz, W. A.

2008-01-01

The end of the performance entitlement historically achieved by classic scaling of CMOS devices is within sight, driven ultimately by fundamental limits. Performance entitlements predicted by classic CMOS scaling have progressively failed to be realized in recent process generations due to excessive leakage, increasing interconnect delays and scaling of gate dielectrics. Prior to reaching fundamental limits, trends in technology, architecture and economics will pressure the industry to adopt new paradigms. A likely response is to repartition system functions away from digital implementations and into new architectures. Future architectures for visual communications will require extending the implementation into the optical and analog processing domains. The fundamental properties of these domains will in turn give rise to new architectural concepts. The limits of CMOS scaling and impact on architectures will be briefly reviewed. Alternative approaches in the optical, electronic and analog domains will then be examined for advantages, architectural impact and drawbacks.

Model-centric approaches for the development of health information systems.

PubMed

Tuomainen, Mika; Mykkänen, Juha; Luostarinen, Heli; Pöyhölä, Assi; Paakkanen, Esa

2007-01-01

Modeling is used increasingly in healthcare to increase shared knowledge, to improve the processes, and to document the requirements of the solutions related to health information systems (HIS). There are numerous modeling approaches which aim to support these aims, but a careful assessment of their strengths, weaknesses and deficiencies is needed. In this paper, we compare three model-centric approaches in the context of HIS development: the Model-Driven Architecture, Business Process Modeling with BPMN and BPEL and the HL7 Development Framework. The comparison reveals that all these approaches are viable candidates for the development of HIS. However, they have distinct strengths and abstraction levels, they require local and project-specific adaptation and offer varying levels of automation. In addition, illustration of the solutions to the end users must be improved.

Modeling interdependencies between business and communication processes in hospitals.

PubMed

Brigl, Birgit; Wendt, Thomas; Winter, Alfred

2003-01-01

The optimization and redesign of business processes in hospitals is an important challenge for the hospital information management who has to design and implement a suitable HIS architecture. Nevertheless, there are no tools available specializing in modeling information-driven business processes and the consequences on the communication between information processing, tools. Therefore, we will present an approach which facilitates the representation and analysis of business processes and resulting communication processes between application components and their interdependencies. This approach aims not only to visualize those processes, but to also to evaluate if there are weaknesses concerning the information processing infrastructure which hinder the smooth implementation of the business processes.

Process-oriented integration and coordination of healthcare services across organizational boundaries.

PubMed

Tello-Leal, Edgar; Chiotti, Omar; Villarreal, Pablo David

2012-12-01

The paper presents a methodology that follows a top-down approach based on a Model-Driven Architecture for integrating and coordinating healthcare services through cross-organizational processes to enable organizations providing high quality healthcare services and continuous process improvements. The methodology provides a modeling language that enables organizations conceptualizing an integration agreement, and identifying and designing cross-organizational process models. These models are used for the automatic generation of: the private view of processes each organization should perform to fulfill its role in cross-organizational processes, and Colored Petri Net specifications to implement these processes. A multi-agent system platform provides agents able to interpret Colored Petri-Nets to enable the communication between the Healthcare Information Systems for executing the cross-organizational processes. Clinical documents are defined using the HL7 Clinical Document Architecture. This methodology guarantees that important requirements for healthcare services integration and coordination are fulfilled: interoperability between heterogeneous Healthcare Information Systems; ability to cope with changes in cross-organizational processes; guarantee of alignment between the integrated healthcare service solution defined at the organizational level and the solution defined at technological level; and the distributed execution of cross-organizational processes keeping the organizations autonomy.

Model-driven requirements engineering (MDRE) for real-time ultra-wide instantaneous bandwidth signal simulation

NASA Astrophysics Data System (ADS)

Chang, Daniel Y.; Rowe, Neil C.

2013-05-01

While conducting a cutting-edge research in a specific domain, we realize that (1) requirements clarity and correctness are crucial to our success [1], (2) hardware is hard to change, most work is in software requirements development, coding and testing [2], (3) requirements are constantly changing, so that configurability, reusability, scalability, adaptability, modularity and testability are important non-functional attributes [3], (4) cross-domain knowledge is necessary for complex systems [4], and (5) if our research is successful, the results could be applied to other domains with similar problems. In this paper, we propose to use model-driven requirements engineering (MDRE) to model and guide our requirements/development, since models are easy to understand, execute, and modify. The domain for our research is Electronic Warfare (EW) real-time ultra-wide instantaneous bandwidth (IBW1) signal simulation. The proposed four MDRE models are (1) Switch-and-Filter architecture, (2) multiple parallel data bit streams alignment, (3) post-ADC and pre-DAC bits re-mapping, and (4) Discrete Fourier Transform (DFT) filter bank. This research is unique since the instantaneous bandwidth we are dealing with is in gigahertz range instead of conventional megahertz.

Generic Software Architecture for Launchers

NASA Astrophysics Data System (ADS)

Carre, Emilien; Gast, Philippe; Hiron, Emmanuel; Leblanc, Alain; Lesens, David; Mescam, Emmanuelle; Moro, Pierre

2015-09-01

The definition and reuse of generic software architecture for launchers is not so usual for several reasons: the number of European launcher families is very small (Ariane 5 and Vega for these last decades); the real time constraints (reactivity and determinism needs) are very hard; low levels of versatility are required (implying often an ad hoc development of the launcher mission). In comparison, satellites are often built on a generic platform made up of reusable hardware building blocks (processors, star-trackers, gyroscopes, etc.) and reusable software building blocks (middleware, TM/TC, On Board Control Procedure, etc.). If some of these reasons are still valid (e.g. the limited number of development), the increase of the available CPU power makes today an approach based on a generic time triggered middleware (ensuring the full determinism of the system) and a centralised mission and vehicle management (offering more flexibility in the design and facilitating the long term maintenance) achievable. This paper presents an example of generic software architecture which could be envisaged for future launchers, based on the previously described principles and supported by model driven engineering and automatic code generation.

Sirepo - Warp

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

Nagler, Robert; Moeller, Paul

Sirepo is an open source framework for cloud computing. The graphical user interface (GUI) for Sirepo, also known as the client, executes in any HTML5 compliant web browser on any computing platform, including tablets. The client is built in JavaScript, making use of the following open source libraries: Bootstrap, which is fundamental for cross-platform web applications; AngularJS, which provides a model–view–controller (MVC) architecture and GUI components; and D3.js, which provides interactive plots and data-driven transformations. The Sirepo server is built on the following Python technologies: Flask, which is a lightweight framework for web development; Jin-ja, which is a secure andmore » widely used templating language; and Werkzeug, a utility library that is compliant with the WSGI standard. We use Nginx as the HTTP server and proxy, which provides a scalable event-driven architecture. The physics codes supported by Sirepo execute inside a Docker container. One of the codes supported by Sirepo is Warp. Warp is a particle-in-cell (PIC) code de-signed to simulate high-intensity charged particle beams and plasmas in both the electrostatic and electromagnetic regimes, with a wide variety of integrated physics models and diagnostics. At pre-sent, Sirepo supports a small subset of Warp’s capabilities. Warp is open source and is part of the Berkeley Lab Accelerator Simulation Toolkit.« less

The influence of foreign vs. North American emissions on surface ozone in the US

NASA Astrophysics Data System (ADS)

Reidmiller, D. R.; Fiore, A. M.; Jaffe, D. A.; Bergmann, D.; Cuvelier, C.; Dentener, F. J.; Duncan, B. N.; Folberth, G.; Gauss, M.; Gong, S.; Hess, P.; Jonson, J. E.; Keating, T.; Lupu, A.; Marmer, E.; Park, R.; Schultz, M. G.; Shindell, D. T.; Szopa, S.; Vivanco, M. G.; Wild, O.; Zuber, A.

2009-03-01

As part of the Hemispheric Transport of Air Pollution (HTAP; http://www.htap.org/) project, we analyze results from 16 global and hemispheric chemical transport models and compare these to Clean Air Status and Trends Network (CASTNet) observations in the United States (US) for 2001. Using the policy-relevant maximum daily 8-h ozone (MDA8 O3) statistic, the multi-model ensemble represents the observations well (mean r2=0.57, ensemble bias=+4.1 ppbv for all regions and all seasons) despite a wide range in the individual model results. Correlations are strongest in the NorthEastern US during spring and fall (r2=0.68); and weakest in the Midwestern US in summer (r2=0.46). However, large positive mean biases exist during summer for all Eastern US regions, ranging from 10-20 ppbv, and a smaller negative bias is present in the Western US during spring (~3 ppbv). In most all other regions and seasons, the biases of the model ensemble simulations are ≤5 ppbv. Sensitivity simulations in which anthropogenic O3-precursor emissions (NOx+NMVOC+CO+aerosols) were decreased by 20% in each of four source regions: East Asia (EA), South Asia (SA), Europe (EU) and North America (NA) show that the greatest response of MDA8 O3 to the summed foreign emissions reductions occurs during spring in the West (0.9 ppbv reduction due to 20% reductions from EA+SA+EU). East Asia is the largest contributor to MDA8 O3 at all ranges of the O3 distribution for most regions (typically ~0.45 ppbv). The exception is in the NorthEastern US where European emissions reductions had the greatest impact on MDA8 O3, particularly in the middle of the MDA8 O3 distribution (response of ~0.35 ppbv between 35-55 ppbv). In all regions and seasons, however, O3-precursor emissions reductions of 20% in the NA source region decrease MDA8 O3 the most - by a factor of 2 to nearly 10 relative to foreign emissions reductions. The O3 response to anthropogenic NA emissions is greatest in the Eastern US during summer at the high end of the O3 distribution (5-6 ppbv for 20% reductions). While the impact of foreign emissions on surface O3 in the US is not negligible - and is of increasing concern given the growth in emissions upwind of the US - domestic emissions reductions remain a far more effective means of decreasing MDA8 O3 values, particularly those above 75 ppb (the current US standard).

A disassembly-driven mechanism explains F-actin-mediated chromosome transport in starfish oocytes

PubMed Central

Bun, Philippe; Dmitrieff, Serge; Belmonte, Julio M

2018-01-01

While contraction of sarcomeric actomyosin assemblies is well understood, this is not the case for disordered networks of actin filaments (F-actin) driving diverse essential processes in animal cells. For example, at the onset of meiosis in starfish oocytes a contractile F-actin network forms in the nuclear region transporting embedded chromosomes to the assembling microtubule spindle. Here, we addressed the mechanism driving contraction of this 3D disordered F-actin network by comparing quantitative observations to computational models. We analyzed 3D chromosome trajectories and imaged filament dynamics to monitor network behavior under various physical and chemical perturbations. We found no evidence of myosin activity driving network contractility. Instead, our observations are well explained by models based on a disassembly-driven contractile mechanism. We reconstitute this disassembly-based contractile system in silico revealing a simple architecture that robustly drives chromosome transport to prevent aneuploidy in the large oocyte, a prerequisite for normal embryonic development. PMID:29350616

Advanced Mirror Technology Development (AMTD) Project: 3.0 Year Status

NASA Technical Reports Server (NTRS)

Stahl, H. Philip

2015-01-01

Advanced Mirror Technology Development (AMTD) is a funded NASA Strategic Astrophysics Technology project. Begun in 2011, we are in Phase 2 of a multi-year effort. Our objective is to mature towards TRL6 critical technologies needed to produce 4-m or larger flight-qualified UVOIR mirrors by 2018 so that a viable astronomy mission can be considered by the 2020 Decadal Review. The developed technology must enable missions capable of both general astrophysics and ultra-high contrast observations of exoplanets. Just as JWST's architecture was driven by launch vehicle, a future UVOIR mission's architecture (monolithic, segmented or interferometric) will depend on capacities of future launch vehicles (and budget). Since we cannot predict the future, we must prepare for all potential futures. Therefore, we are pursuing multiple technology paths. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND result in a high-performance low-cost low-risk system. One of our key accomplishments is that we have derived engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicle and its inherent mass and volume constraints. Another key accomplishment is that we have matured our technology by building and testing hardware. To demonstrate stacked core technology, we built a 400 mm thick mirror. Currently, to demonstrate lateral scalability, we are manufacturing a 1.5 meter mirror. To assist in architecture trade studies, the Engineering team develops Structural, Thermal and Optical Performance (STOP) models of candidate mirror assembly systems including substrates, structures, and mechanisms. These models are validated by test of full- and subscale components in relevant thermo-vacuum environments. Specific analyses include: maximum mirror substrate size, first fundamental mode frequency (i.e., stiffness) and mass required to fabricate without quilting, survive launch, and achieve stable pointing and maximum thermal time constant.

Security in the Cache and Forward Architecture for the Next Generation Internet

NASA Astrophysics Data System (ADS)

Hadjichristofi, G. C.; Hadjicostis, C. N.; Raychaudhuri, D.

The future Internet architecture will be comprised predominately of wireless devices. It is evident at this stage that the TCP/IP protocol that was developed decades ago will not properly support the required network functionalities since contemporary communication profiles tend to be data-driven rather than host-based. To address this paradigm shift in data propagation, a next generation architecture has been proposed, the Cache and Forward (CNF) architecture. This research investigates security aspects of this new Internet architecture. More specifically, we discuss content privacy, secure routing, key management and trust management. We identify security weaknesses of this architecture that need to be addressed and we derive security requirements that should guide future research directions. Aspects of the research can be adopted as a step-stone as we build the future Internet.

Progress and Impact of 13 Years of the Global Programme to Eliminate Lymphatic Filariasis on Reducing the Burden of Filarial Disease

PubMed Central

Ramaiah, K. D.; Ottesen, Eric A.

2014-01-01

Background A Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, with mass drug administration (MDA) as the core strategy of the programme. After completing 13 years of operations through 2012 and with MDA in place in 55 of 73 endemic countries, the impact of the MDA programme on microfilaraemia, hydrocele and lymphedema is in need of being assessed. Methodology/Principal findings During 2000–2012, the MDA programme made remarkable achievements – a total of 6.37 billion treatments were offered and an estimated 4.45 billion treatments were consumed by the population living in endemic areas. Using a model based on empirical observations of the effects of treatment on clinical manifestations, it is estimated that 96.71 million LF cases, including 79.20 million microfilaria carriers, 18.73 million hydrocele cases and a minimum of 5.49 million lymphedema cases have been prevented or cured during this period. Consequently, the global prevalence of LF is calculated to have fallen by 59%, from 3.55% to 1.47%. The fall was highest for microfilaraemia prevalence (68%), followed by 49% in hydrocele prevalence and 25% in lymphedema prevalence. It is estimated that, currently, i.e. after 13 years of the MDA programme, there are still an estimated 67.88 million LF cases that include 36.45 million microfilaria carriers, 19.43 million hydrocele cases and 16.68 million lymphedema cases. Conclusions/Significance The MDA programme has resulted in significant reduction of the LF burden. Extension of MDA to all at-risk countries and to all regions within those countries where MDA has not yet reached 100% geographic coverage is imperative to further reduce the number of microfilaraemia and chronic disease cases and to reach the global target of interrupting transmission of LF by 2020. PMID:25412180

Sericin improves heart and liver mitochondrial architecture in hypercholesterolaemic rats and maintains pancreatic and adrenal cell biosynthesis.

PubMed

Ampawong, Sumate; Isarangkul, Duangnate; Aramwit, Pornanong

2017-09-15

Hypercholesterolaemia is well known to be associated with mitochondrial dysfunction, subsequently leading to multiple organ failure. Similar to other natural products, sericin is a candidate for adjunctive therapy in hyperlipidaemic conditions. However, the cholesterol-lowering mechanisms of sericin are multifactorial and controversial. Here, a high-cholesterol-fed rat model with or without sericin treatment was established using a dosage of 1000mg/kg/day for 30 days. Blood lipid profiles, oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; nuclear factor erythroid 2-related factor, Nrf-2), dysmorphic mitochondria in relation to fission (dynamin-related protein-1; Drp-1) and fusion (guanosine triphosphatase mutated in dominant optic atrophy; OPA-1) markers and biosynthetic markers (aquaporin, AQP-1; tubulin-4β, Tb4B) in the pancreas and adrenal gland were evaluated. The results showed that sericin reduced blood cholesterol and increased high-density lipoprotein (HDL) by acting against oxidative stress. Hypocholesterolaemic and antioxidant conditions further preserved heart and liver mitochondrial architecture; however, this protection was not exhibited in the kidney, where a high level of renal mitophagy, indicating by LC-3 up-regulation, was presented. The steps of ultrastructural alteration of mitochondria from degenerative changes to necrosis were also demonstrated. Sericin also conserved AQP-1 and Tb4B levels in the exocrine pancreatic acinar cells and zona glomerulosa cells, which were positively correlated with serum lipase, HDL, antioxidative markers and mitochondrial integrity. The present study revealed that sericin not only has antioxidant capacity but also balances pancreatic and adrenal cell biosynthesis, especially lipase activity, which may have played an important role in improving lipid dysregulation in the hypercholesterolaemic rat model, leading to the reduction of dysmorphic mitochondria, particularly in the heart and liver. Copyright © 2017 Elsevier Inc. All rights reserved.

mda-7/IL-24 induces cell death in neuroblastoma through a novel mechanism involving AIF and ATM

PubMed Central

Bhoopathi, Praveen; Lee, Nathaniel; Pradhan, Anjan K.; Shen, Xue-Ning; Das, Swadesh K.; Sarkar, Devanand; Emdad, Luni; Fisher, Paul B.

2016-01-01

Advanced stages of neuroblastoma, the most common extracranial malignant solid tumor of the central nervous system in infants and children, are refractive to therapy. Ectopic expression of melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) promotes broad-spectrum antitumor activity in vitro, in vivo in pre-clinical animal models and in a Phase I clinical trial in patients with advanced cancers, without harming normal cells. mda-7/IL-24 exerts cancer-specific toxicity (apoptosis or toxic autophagy) by promoting ER stress and modulating multiple signal transduction pathways regulating cancer cell growth, invasion, metastasis, survival and angiogenesis. To enhance cancer-selective expression and targeted anti-cancer activity of mda-7/IL-24 we created a tropism-modified Cancer Terminator Virus (Ad.5/3-CTV), which selectively replicates in cancer cells producing robust expression of mda-7/IL-24. We now show that Ad.5/3-CTV induces profound neuroblastoma anti-proliferative activity and apoptosis in a caspase 3/9-independent manner both in vitro and in vivo in a tumor xenograft model. Ad.5/3-CTV promotes these effects through a unique pathway involving apoptosis inducing factor (AIF) translocation into the nucleus. Inhibiting AIF rescued neuroblastoma cells from Ad.5/3-CTV-induced cell death, whereas pan-caspase inhibition failed to promote survival. Ad.5/3-CTV infection of neuroblastoma cells increased ATM phosphorylation instigating nuclear translocation and increased γ–H2AX, triggering nuclear translocation and intensified expression of AIF. These results were validated further using two ATM small molecule inhibitors that attenuated PARP cleavage by inhibiting γ–H2AX, which in turn inhibited AIF changes in Ad.5/3-CTV-infected neuroblastoma cells. Taken together, we elucidate a novel pathway for mda-7/IL-24-induced caspase-independent apoptosis in neuroblastoma cells mediated through modulation of AIF, ATM and γ–H2AX. PMID:27197168

A Distributed Architecture for Tsunami Early Warning and Collaborative Decision-support in Crises

NASA Astrophysics Data System (ADS)

Moßgraber, J.; Middleton, S.; Hammitzsch, M.; Poslad, S.

2012-04-01

The presentation will describe work on the system architecture that is being developed in the EU FP7 project TRIDEC on "Collaborative, Complex and Critical Decision-Support in Evolving Crises". The challenges for a Tsunami Early Warning System (TEWS) are manifold and the success of a system depends crucially on the system's architecture. A modern warning system following a system-of-systems approach has to integrate various components and sub-systems such as different information sources, services and simulation systems. Furthermore, it has to take into account the distributed and collaborative nature of warning systems. In order to create an architecture that supports the whole spectrum of a modern, distributed and collaborative warning system one must deal with multiple challenges. Obviously, one cannot expect to tackle these challenges adequately with a monolithic system or with a single technology. Therefore, a system architecture providing the blueprints to implement the system-of-systems approach has to combine multiple technologies and architectural styles. At the bottom layer it has to reliably integrate a large set of conventional sensors, such as seismic sensors and sensor networks, buoys and tide gauges, and also innovative and unconventional sensors, such as streams of messages from social media services. At the top layer it has to support collaboration on high-level decision processes and facilitates information sharing between organizations. In between, the system has to process all data and integrate information on a semantic level in a timely manner. This complex communication follows an event-driven mechanism allowing events to be published, detected and consumed by various applications within the architecture. Therefore, at the upper layer the event-driven architecture (EDA) aspects are combined with principles of service-oriented architectures (SOA) using standards for communication and data exchange. The most prominent challenges on this layer include providing a framework for information integration on a syntactic and semantic level, leveraging distributed processing resources for a scalable data processing platform, and automating data processing and decision support workflows.

Multidimensional assessment of severe asthma: A systematic review and meta-analysis.

PubMed

Clark, Vanessa L; Gibson, Peter G; Genn, Grayson; Hiles, Sarah A; Pavord, Ian D; McDonald, Vanessa M

2017-10-01

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes. © 2017 Asian Pacific Society of Respirology.

Exhaled breath malondialdehyde, spirometric results and dust exposure assessment in ceramics production workers.

PubMed

Sakhvidi, Mohammad Javad Zare; Biabani Ardekani, Javad; Firoozichahak, Ali; Zavarreza, Javad; Hajaghazade, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amirhooshang; Barkhordari, Abolfazl

2015-01-01

The study aimed at measuring exhaled breath malondialdehyde (EBC-MDA) in workers exposed to dust containing silica and at its comparison with the non-exposed control group. The cross sectional, case-control study (N = 50) was performed in a tile and ceramics production factory in Yazd, Iran. EBC-MDA was quantified in exhaled breath of the participants by a lab made breath sampler. Exposure intensity was measured according to the NIOSH 0600 method in selected homogeneous exposure groups. Additionally, spirometry test was conducted to investigate a correlation between EBC-MDA and spirometric findings in the exposed workers. There was no difference in the observed exposure intensities of silica containing dust in different units. However, "coating preparation" was the unit with the highest concentration of dust. Although, the level of EBC-MDA in the cases was slightly higher than in the controls, the difference was not statistically significant (U = 252, p = 0.464). A significant and positive correlation was found between dust exposure intensity in working units and the measured EBC-MDA of workers (r = 0.467, N = 25, p = 0.027). There were also no statistically significant differences among job categories in the exposed group for the values of FEV1% (F(3, 44) = 0.656, p = 0.584), FVC% (F(3, 44) = 1.417, p = 0.172), and FEV1/FVC% (F(3, 44) = 1.929, p = 0.139). The results showed a significant correlation between respirable dust exposure intensity and the level of EBC-MDA of the exposed subjects. However, our results did not show a significant correlation between lung function decreases and EBC-MDA. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Characterization of the canine mda-7 gene, transcripts and expression patterns

PubMed Central

Sandey, Maninder; Bird, R. Curtis; Das, Swadesh K.; Sarkar, Devanand; Curiel, David T.; Fisher, Paul B.; Smith, Bruce F.

2014-01-01

Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) displays potent growth suppressing and cell killing activity against a wide variety of human and rodent cancer cells. In this study, we identified a canine ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family members on chromosome 7. The full-length mRNA sequence of canine mda-7 was determined, which encodes a 186-amino acid protein that has 66% similarity to human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal canine epidermal keratinocytes (NCEKs), and its expression levels are increased after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5′-splice donor sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus (signal peptide sequence) and are dissimilar in amino acid sequences at their C-terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most tumor derived cancer cell lines tested, like its human counterpart. Unlike human MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA) stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in-silico analysis revealed that canonical canine MDA-7 has a potential 28 amino acid signal peptide sequence that can target it for active secretion. This data suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its protein product has high amino acid similarity to human MDA-7/IL-24 protein and it may possess similar biological properties to human MDA-7/IL-24, but its expression pattern is more restricted than its human ortholog. PMID:24865935

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines

PubMed Central

Ndeffo Mbah, Martial; Galvani, Alison

2017-01-01

Background Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. Methods and findings We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person’s susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years’ durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails’ rate of patency and lifespan, and force of infection to snails. Conclusions To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms. PMID:28410369

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

PubMed

Alsallaq, Ramzi A; Gurarie, David; Ndeffo Mbah, Martial; Galvani, Alison; King, Charles

2017-04-01

Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person's susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years' durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails' rate of patency and lifespan, and force of infection to snails. To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms.

INFORM Lab: a testbed for high-level information fusion and resource management

NASA Astrophysics Data System (ADS)

Valin, Pierre; Guitouni, Adel; Bossé, Eloi; Wehn, Hans; Happe, Jens

2011-05-01

DRDC Valcartier and MDA have created an advanced simulation testbed for the purpose of evaluating the effectiveness of Network Enabled Operations in a Coastal Wide Area Surveillance situation, with algorithms provided by several universities. This INFORM Lab testbed allows experimenting with high-level distributed information fusion, dynamic resource management and configuration management, given multiple constraints on the resources and their communications networks. This paper describes the architecture of INFORM Lab, the essential concepts of goals and situation evidence, a selected set of algorithms for distributed information fusion and dynamic resource management, as well as auto-configurable information fusion architectures. The testbed provides general services which include a multilayer plug-and-play architecture, and a general multi-agent framework based on John Boyd's OODA loop. The testbed's performance is demonstrated on 2 types of scenarios/vignettes for 1) cooperative search-and-rescue efforts, and 2) a noncooperative smuggling scenario involving many target ships and various methods of deceit. For each mission, an appropriate subset of Canadian airborne and naval platforms are dispatched to collect situation evidence, which is fused, and then used to modify the platform trajectories for the most efficient collection of further situation evidence. These platforms are fusion nodes which obey a Command and Control node hierarchy.

What Can Causal Networks Tell Us about Metabolic Pathways?

PubMed Central

Blair, Rachael Hageman; Kliebenstein, Daniel J.; Churchill, Gary A.

2012-01-01

Graphical models describe the linear correlation structure of data and have been used to establish causal relationships among phenotypes in genetic mapping populations. Data are typically collected at a single point in time. Biological processes on the other hand are often non-linear and display time varying dynamics. The extent to which graphical models can recapitulate the architecture of an underlying biological processes is not well understood. We consider metabolic networks with known stoichiometry to address the fundamental question: “What can causal networks tell us about metabolic pathways?”. Using data from an Arabidopsis BaySha population and simulated data from dynamic models of pathway motifs, we assess our ability to reconstruct metabolic pathways using graphical models. Our results highlight the necessity of non-genetic residual biological variation for reliable inference. Recovery of the ordering within a pathway is possible, but should not be expected. Causal inference is sensitive to subtle patterns in the correlation structure that may be driven by a variety of factors, which may not emphasize the substrate-product relationship. We illustrate the effects of metabolic pathway architecture, epistasis and stochastic variation on correlation structure and graphical model-derived networks. We conclude that graphical models should be interpreted cautiously, especially if the implied causal relationships are to be used in the design of intervention strategies. PMID:22496633

A Multi-mission Event-Driven Component-Based System for Support of Flight Software Development, ATLO, and Operations first used by the Mars Science Laboratory (MSL) Project

NASA Technical Reports Server (NTRS)

Dehghani, Navid; Tankenson, Michael

2006-01-01

This viewgraph presentation reviews the architectural description of the Mission Data Processing and Control System (MPCS). MPCS is an event-driven, multi-mission ground data processing components providing uplink, downlink, and data management capabilities which will support the Mars Science Laboratory (MSL) project as its first target mission. MPCS is designed with these factors (1) Enabling plug and play architecture (2) MPCS has strong inheritance from GDS components that have been developed for other Flight Projects (MER, MRO, DAWN, MSAP), and are currently being used in operations and ATLO, and (3) MPCS components are Java-based, platform independent, and are designed to consume and produce XML-formatted data

Space Missions Trade Space Generation and Assessment Using JPL Rapid Mission Architecture (RMA) Team Approach

NASA Technical Reports Server (NTRS)

Moeller, Robert C.; Borden, Chester; Spilker, Thomas; Smythe, William; Lock, Robert

2011-01-01

The JPL Rapid Mission Architecture (RMA) capability is a novel collaborative team-based approach to generate new mission architectures, explore broad trade space options, and conduct architecture-level analyses. RMA studies address feasibility and identify best candidates to proceed to further detailed design studies. Development of RMA first began at JPL in 2007 and has evolved to address the need for rapid, effective early mission architectural development and trade space exploration as a precursor to traditional point design evaluations. The RMA approach integrates a small team of architecture-level experts (typically 6-10 people) to generate and explore a wide-ranging trade space of mission architectures driven by the mission science (or technology) objectives. Group brainstorming and trade space analyses are conducted at a higher level of assessment across multiple mission architectures and systems to enable rapid assessment of a set of diverse, innovative concepts. This paper describes the overall JPL RMA team, process, and high-level approach. Some illustrative results from previous JPL RMA studies are discussed.

Impact of Material and Architecture Model Parameters on the Failure of Woven Ceramic Matrix Composites (CMCs) via the Multiscale Generalized Method of Cells

NASA Technical Reports Server (NTRS)

Liu, Kuang C.; Arnold, Steven M.

2011-01-01

It is well known that failure of a material is a locally driven event. In the case of ceramic matrix composites (CMCs), significant variations in the microstructure of the composite exist and their significance on both deformation and life response need to be assessed. Examples of these variations include changes in the fiber tow shape, tow shifting/nesting and voids within and between tows. In the present work, the effects of many of these architectural parameters and material scatter of woven ceramic composite properties at the macroscale (woven RUC) will be studied to assess their sensitivity. The recently developed Multiscale Generalized Method of Cells methodology is used to determine the overall deformation response, proportional elastic limit (first matrix cracking), and failure under tensile loading conditions. The macroscale responses investigated illustrate the effect of architectural and material parameters on a single RUC representing a five harness satin weave fabric. Results shows that the most critical architectural parameter is weave void shape and content with other parameters being less in severity. Variation of the matrix material properties was also studied to illustrate the influence of the material variability on the overall features of the composite stress-strain response.

Myotonic Muscular Dystrophy

MedlinePlus

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Dshell++: A Component Based, Reusable Space System Simulation Framework

NASA Technical Reports Server (NTRS)

Lim, Christopher S.; Jain, Abhinandan

2009-01-01

This paper describes the multi-mission Dshell++ simulation framework for high fidelity, physics-based simulation of spacecraft, robotic manipulation and mobility systems. Dshell++ is a C++/Python library which uses modern script driven object-oriented techniques to allow component reuse and a dynamic run-time interface for complex, high-fidelity simulation of spacecraft and robotic systems. The goal of the Dshell++ architecture is to manage the inherent complexity of physicsbased simulations while supporting component model reuse across missions. The framework provides several features that support a large degree of simulation configurability and usability.

Reconfiguration of Brain Network Architectures between Resting-State and Complexity-Dependent Cognitive Reasoning.

PubMed

Hearne, Luke J; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

2017-08-30

Our capacity for higher cognitive reasoning has a measurable limit. This limit is thought to arise from the brain's capacity to flexibly reconfigure interactions between spatially distributed networks. Recent work, however, has suggested that reconfigurations of task-related networks are modest when compared with intrinsic "resting-state" network architecture. Here we combined resting-state and task-driven functional magnetic resonance imaging to examine how flexible, task-specific reconfigurations associated with increasing reasoning demands are integrated within a stable intrinsic brain topology. Human participants (21 males and 28 females) underwent an initial resting-state scan, followed by a cognitive reasoning task involving different levels of complexity, followed by a second resting-state scan. The reasoning task required participants to deduce the identity of a missing element in a 4 × 4 matrix, and item difficulty was scaled parametrically as determined by relational complexity theory. Analyses revealed that external task engagement was characterized by a significant change in functional brain modules. Specifically, resting-state and null-task demand conditions were associated with more segregated brain-network topology, whereas increases in reasoning complexity resulted in merging of resting-state modules. Further increments in task complexity did not change the established modular architecture, but affected selective patterns of connectivity between frontoparietal, subcortical, cingulo-opercular, and default-mode networks. Larger increases in network efficiency within the newly established task modules were associated with higher reasoning accuracy. Our results shed light on the network architectures that underlie external task engagement, and highlight selective changes in brain connectivity supporting increases in task complexity. SIGNIFICANCE STATEMENT Humans have clear limits in their ability to solve complex reasoning problems. It is thought that such limitations arise from flexible, moment-to-moment reconfigurations of functional brain networks. It is less clear how such task-driven adaptive changes in connectivity relate to stable, intrinsic networks of the brain and behavioral performance. We found that increased reasoning demands rely on selective patterns of connectivity within cortical networks that emerged in addition to a more general, task-induced modular architecture. This task-driven architecture reverted to a more segregated resting-state architecture both immediately before and after the task. These findings reveal how flexibility in human brain networks is integral to achieving successful reasoning performance across different levels of cognitive demand. Copyright © 2017 the authors 0270-6474/17/378399-13$15.00/0.

Fault tolerant architectures for integrated aircraft electronics systems, task 2

NASA Technical Reports Server (NTRS)

Levitt, K. N.; Melliar-Smith, P. M.; Schwartz, R. L.

1984-01-01

The architectural basis for an advanced fault tolerant on-board computer to succeed the current generation of fault tolerant computers is examined. The network error tolerant system architecture is studied with particular attention to intercluster configurations and communication protocols, and to refined reliability estimates. The diagnosis of faults, so that appropriate choices for reconfiguration can be made is discussed. The analysis relates particularly to the recognition of transient faults in a system with tasks at many levels of priority. The demand driven data-flow architecture, which appears to have possible application in fault tolerant systems is described and work investigating the feasibility of automatic generation of aircraft flight control programs from abstract specifications is reported.

Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor.

PubMed

Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Soloveva, Veronica; Venkatesan, Aranapakam; Dehnhardt, Christoph; Delos Santos, Efren; Chen, Zecheng; Dos Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Gibbons, Jay

2010-04-01

PKI-402 is a selective, reversible, ATP-competitive, equipotent inhibitor of class I phosphatidylinositol 3-kinases (PI3K), including PI3K-alpha mutants, and mammalian target of rapamycin (mTOR; IC(50) versus PI3K-alpha = 2 nmol/L). PKI-402 inhibited growth of human tumor cell lines derived from breast, brain (glioma), pancreas, and non-small cell lung cancer tissue and suppressed phosphorylation of PI3K and mTOR effector proteins (e.g., Akt at T308) at concentrations that matched those that inhibited cell growth. In MDA-MB-361 [breast: Her2(+) and PIK3CA mutant (E545K)], 30 nmol/L PKI-402 induced cleaved poly(ADP-ribose) polymerase (PARP), a marker for apoptosis. In vivo, PKI-402 inhibited tumor growth in MDA-MB-361, glioma (U87MG), and lung (A549) xenograft models. In MDA-MB-361, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduced initial tumor volume of 260 mm(3) to 129 mm(3) and prevented tumor regrowth for 70 days. In MDA-MB-361 tumors, PKI-402 (100 mg/kg, single dose) suppressed Akt phosphorylation (at T308) and induced cleaved PARP. Suppression of phosphorylated Akt (p-Akt) was complete at 8 hours and still evident at 24 hours. Cleaved PARP was evident at 8 and 24 hours. In normal tissue (heart and lung), PKI-402 (100 mg/kg) had minimal effect on p-Akt, with no detectable cleaved PARP. Preferential accumulation of PKI-402 in tumor tissue was observed. Complete, sustained suppression of Akt phosphorylation may cause tumor regression in MDA-MB-361 and other xenograft models. We are testing whether dual PI3K/mTOR inhibitors can durably suppress p-Akt, induce cleaved PARP, and cause tumor regression in a diverse set of human tumor xenograft models. Mol Cancer Ther; 9(4); 976-84. (c)2010 AACR.

Assessing the interruption of the transmission of human helminths with mass drug administration alone: optimizing the design of cluster randomized trials.

PubMed

Anderson, Roy; Farrell, Sam; Turner, Hugo; Walson, Judd; Donnelly, Christl A; Truscott, James

2017-02-17

A method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant). The methodological approach first uses an age-structured deterministic model to predict the MDA coverage required for treating pre-school aged children (Pre-SAC), school aged children (SAC) and adults (Adults) to eliminate transmission (crossing the breakpoint in transmission created by sexual mating in dioecious helminths) with 3 rounds of annual MDA. Stochastic individual-based models are then used to calculate the positive and negative predictive values (PPV and NPV, respectively, for observing elimination or the bounce back of infection) for a defined prevalence of infection 2 years post the cessation of MDA. For the arm only involving the treatment of Pre-SAC and SAC, the failure rate is predicted to be very high (particularly for hookworm-infected villages) unless transmission intensity is very low (R 0 , or the effective reproductive number R, just above unity in value). The calculations are designed to consider various trial arms and stratifications; namely, community-based treatment and Pre-SAC and SAC only treatment (the two arms of the trial), different STH transmission settings of low, medium and high, and different STH species mixes. Results are considered in the light of the complications introduced by the choice of statistic to define success or failure, varying adherence to treatment, migration and parameter uncertainty.

Keep it on the edge: The post-mitotic midbody as a polarity signal unit

PubMed Central

Lujan, Pablo; Rubio, Teresa; Varsano, Giulia; Köhn, Maja

2017-01-01

ABSTRACT The maintenance of the epithelial architecture during tissue proliferation is achieved by apical positioning of the midbody after cell division. Consequently, midbody mislocalization contributes to epithelial architecture disruption, a fundamental event during epithelial tumorigenesis. Studies in 3D polarized epithelial MDCK or Caco2 cell models, where midbody misplacement leads to multiple ectopic but fully polarized lumen-containing cysts, revealed that this phenotype can be caused by 2 different scenarios: the loss of mitotic spindle orientation or the loss of asymmetric abscission. In addition, we have recently proposed a third cellular mechanism where the midbody mislocalization is achieved through cytokinesis acceleration driven by the cancer-promoting phosphatase of regenerating liver (PRL)-3. Here we critically review these findings, and we furthermore present new data indicating that midbodies themselves might act as signal unit for polarization since they can infer apical characteristics to a basal membrane. PMID:28919938

AMP: a science-driven web-based application for the TeraGrid

NASA Astrophysics Data System (ADS)

Woitaszek, M.; Metcalfe, T.; Shorrock, I.

The Asteroseismic Modeling Portal (AMP) provides a web-based interface for astronomers to run and view simulations that derive the properties of Sun-like stars from observations of their pulsation frequencies. In this paper, we describe the architecture and implementation of AMP, highlighting the lightweight design principles and tools used to produce a functional fully-custom web-based science application in less than a year. Targeted as a TeraGrid science gateway, AMP's architecture and implementation are intended to simplify its orchestration of TeraGrid computational resources. AMP's web-based interface was developed as a traditional standalone database-backed web application using the Python-based Django web development framework, allowing us to leverage the Django framework's capabilities while cleanly separating the user interface development from the grid interface development. We have found this combination of tools flexible and effective for rapid gateway development and deployment.

Detection of malondialdehyde in processed meat products without interference from the ingredients.

PubMed

Jung, Samooel; Nam, Ki Chang; Jo, Cheorun

2016-10-15

Our aim was to develop a method for accurate quantification of malondialdehyde (MDA) in meat products. MDA content of uncured ground pork (Control); ground pork cured with sodium nitrite (Nitrite); and ground pork cured with sodium nitrite, sodium chloride, sodium pyrophosphate, maltodextrin, and a sausage seasoning (Mix) was measured by the 2-thiobarbituric acid (TBA) assay with MDA extraction by trichloroacetic acid (method A) and two high-performance liquid chromatography (HPLC) methods: i) HPLC separation of the MDA-dinitrophenyl hydrazine adduct (method B) and ii) HPLC separation of MDA (method C) after MDA extraction with acetonitrile. Methods A and B could not quantify MDA accurately in groups Nitrite and Mix. Nevertheless, MDA in groups Control, Nitrite, and Mix was accurately quantified by method C with good recovery. Therefore, direct MDA quantification by HPLC after MDA extraction with acetonitrile (method C) is useful for accurate measurement of MDA content in processed meat products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells.

PubMed

Katterle, Y; Brandt, B H; Dowdy, S F; Niggemann, B; Zänker, K S; Dittmar, T

2004-01-12

Due to its pivotal role in the growth factor-mediated tumour cell migration, the adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby minimising metastasis formation. Here, we present an approach to block PLC-gamma1 activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1 SH2 domains, which were fused to the TAT-transduction domain to ensure a high protein transduction efficiency. Two proteins were generated containing one PLC-gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%, concomitant with a complete abrogation of the EGF-driven calcium influx. In addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated migration of about 75% combined with a markedly decreased time locomotion of single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast cancer cells, we conclude from our results that the protein-based PLC-gamma1 inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to minimise metastasis formation because of the blockade of cell migration and proliferation.

The prophylactic effect of vitamin C on oxidative stress indexes in rat eyes following exposure to radiofrequency wave generated by a BTS antenna model.

PubMed

Jelodar, Gholamali; Akbari, Abolfazl; Nazifi, Saeed

2013-02-01

This study was conducted to evaluate the effect of radiofrequency wave (RFW)-induced oxidative stress in the eye and the prophylactic effect of vitamin C on this organ by measuring the antioxidant enzymes activity including: glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: Control, vitamin C (L-ascorbic acid 200 mg/kg of body weight/day by gavage), test (exposed to 900 MHz RFW) and the treated group (received vitamin C in addition to exposure to RFW). At the end of the experiment all animals were sacrificed, their eyes were removed and were used for measurement of antioxidant enzymes and MDA activity. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (P < 0.05). In the treated group vitamin C improved antioxidant enzymes activity and reduced MDA compared to the test group (P < 0.05). It can be concluded that RFW causes oxidative stress in the eyes and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Model of rhythmic ball bouncing using a visually controlled neural oscillator.

PubMed

Avrin, Guillaume; Siegler, Isabelle A; Makarov, Maria; Rodriguez-Ayerbe, Pedro

2017-10-01

The present paper investigates the sensory-driven modulations of central pattern generator dynamics that can be expected to reproduce human behavior during rhythmic hybrid tasks. We propose a theoretical model of human sensorimotor behavior able to account for the observed data from the ball-bouncing task. The novel control architecture is composed of a Matsuoka neural oscillator coupled with the environment through visual sensory feedback. The architecture's ability to reproduce human-like performance during the ball-bouncing task in the presence of perturbations is quantified by comparison of simulated and recorded trials. The results suggest that human visual control of the task is achieved online. The adaptive behavior is made possible by a parametric and state control of the limit cycle emerging from the interaction of the rhythmic pattern generator, the musculoskeletal system, and the environment. NEW & NOTEWORTHY The study demonstrates that a behavioral model based on a neural oscillator controlled by visual information is able to accurately reproduce human modulations in a motor action with respect to sensory information during the rhythmic ball-bouncing task. The model attractor dynamics emerging from the interaction between the neuromusculoskeletal system and the environment met task requirements, environmental constraints, and human behavioral choices without relying on movement planning and explicit internal models of the environment. Copyright © 2017 the American Physiological Society.

The Orion GN and C Data-Driven Flight Software Architecture for Automated Sequencing and Fault Recovery

NASA Technical Reports Server (NTRS)

King, Ellis; Hart, Jeremy; Odegard, Ryan

2010-01-01

The Orion Crew Exploration Vehicle (CET) is being designed to include significantly more automation capability than either the Space Shuttle or the International Space Station (ISS). In particular, the vehicle flight software has requirements to accommodate increasingly automated missions throughout all phases of flight. A data-driven flight software architecture will provide an evolvable automation capability to sequence through Guidance, Navigation & Control (GN&C) flight software modes and configurations while maintaining the required flexibility and human control over the automation. This flexibility is a key aspect needed to address the maturation of operational concepts, to permit ground and crew operators to gain trust in the system and mitigate unpredictability in human spaceflight. To allow for mission flexibility and reconfrgurability, a data driven approach is being taken to load the mission event plan as well cis the flight software artifacts associated with the GN&C subsystem. A database of GN&C level sequencing data is presented which manages and tracks the mission specific and algorithm parameters to provide a capability to schedule GN&C events within mission segments. The flight software data schema for performing automated mission sequencing is presented with a concept of operations for interactions with ground and onboard crew members. A prototype architecture for fault identification, isolation and recovery interactions with the automation software is presented and discussed as a forward work item.

Melamine-based dendrimer amine-modified magnetic nanoparticles as an efficient Pb(II) adsorbent for wastewater treatment: Adsorption optimization by response surface methodology.

PubMed

Jiryaei Sharahi, Fatemeh; Shahbazi, Afsaneh

2017-12-01

Magnetic Fe 3 O 4 nanoparticles with an average diameter of 64 nm was synthesized solvothermically and subsequently modified with melamine-based dendrimer amine (MDA-Fe 3 O 4 ) via grafting method. The synthesized materials were characterized using DLS, SEM, XRD, FTIR, VSM, TGA and elemental analysis techniques. The MDA-Fe 3 O 4 was employed for the efficient removal of Pb(II) ions from an aqueous solution. The adsorption efficiency was investigated in relation to the independent variables of Pb(II) concentration (80-250 mg L -1 ), pH of the solution (3-7), adsorbent dosage (0.1-0.5 g L -1 ) and temperature (10-40 °C) via a central composite design (CCD) using response surface methodology (RSM). The significance of independent variables and their interactions was tested using ANOVA at a 95% confidence limit (α = 0.05). A second-order quadratic model was established to predict the adsorption efficiency. Under the optimum condition (initial Pb(II) concentration = 110 mg L -1 , MDA-Fe 3 O 4 dosage = 0.49 g L -1 , pH = 5 and temperature = 30 °C) a removal percentage of 85.6% was obtained. The isotherm data fitted well to the Freundlich model within the concentration range of the experimental study. A maximum adsorption capacity of 333.3 mg g -1 was predicted by the Langmuir model. The adsorption rate of Pb(II) ions onto MDA-Fe 3 O 4 was in good agreement with the pseudo-second-order model (R 2  = 0.999; k 2  = 4.7 × 10 -4  g mg -1 min -1 ). Thermodynamically, adsorption was spontaneous and endothermic. The MDA-Fe 3 O 4 was successfully regenerated using 0.3 M HCl with little loss of adsorption capacity (≈7%) for five successive adsorption cycles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor.

PubMed

Mallon, Robert; Feldberg, Larry R; Lucas, Judy; Chaudhary, Inder; Dehnhardt, Christoph; Santos, Efren Delos; Chen, Zecheng; dos Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Venkatesan, Aranapakam; Hollander, Irwin

2011-05-15

The aim of this study was to show preclinical efficacy and clinical development potential of PKI-587, a dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor. In vitro class 1 PI3K enzyme and human tumor cell growth inhibition assays and in vivo five tumor xenograft models were used to show efficacy. In vitro, PKI-587 potently inhibited class I PI3Ks (IC(50) vs. PI3K-α = 0.4 nmol/L), PI3K-α mutants, and mTOR. PKI-587 inhibited growth of 50 diverse human tumor cell lines at IC(50) values of less than 100 nmol/L. PKI-587 suppressed phosphorylation of PI3K/mTOR effectors (e.g., Akt), and induced apoptosis in human tumor cell lines with elevated PI3K/mTOR signaling. MDA-MB-361 [breast; HER2(+), PIK3CA mutant (E545K)] was particularly sensitive to this effect, with cleaved PARP, an apoptosis marker, induced by 30 nmol/L PKI-587 at 4 hours. In vivo, PKI-587 inhibited tumor growth in breast (MDA-MB-361, BT474), colon (HCT116), lung (H1975), and glioma (U87MG) xenograft models. In MDA-MB-361 tumors, PKI-587 (25 mg/kg, single dose i.v.) suppressed Akt phosphorylation [at threonine(T)308 and serine(S)473] for up to 36 hours, with cleaved PARP (cPARP) evident up to 18 hours. PKI-587 at 25 mg/kg (once weekly) shrank large (∼1,000 mm(3)) MDA-MB-361 tumors and suppressed tumor regrowth. Tumor regression correlated with suppression of phosphorylated Akt in the MDA-MB-361 model. PKI-587 also caused regression in other tumor models, and efficacy was enhanced when given in combination with PD0325901 (MEK 1/2 inhibitor), irinotecan (topoisomerase I inhibitor), or HKI-272 (neratinib, HER2 inhibitor). Significant antitumor efficacy and a favorable pharmacokinetic/safety profile justified phase 1 clinical evaluation of PKI-587. ©2011 AACR.

Federated ontology-based queries over cancer data

PubMed Central

2012-01-01

Background Personalised medicine provides patients with treatments that are specific to their genetic profiles. It requires efficient data sharing of disparate data types across a variety of scientific disciplines, such as molecular biology, pathology, radiology and clinical practice. Personalised medicine aims to offer the safest and most effective therapeutic strategy based on the gene variations of each subject. In particular, this is valid in oncology, where knowledge about genetic mutations has already led to new therapies. Current molecular biology techniques (microarrays, proteomics, epigenetic technology and improved DNA sequencing technology) enable better characterisation of cancer tumours. The vast amounts of data, however, coupled with the use of different terms - or semantic heterogeneity - in each discipline makes the retrieval and integration of information difficult. Results Existing software infrastructures for data-sharing in the cancer domain, such as caGrid, support access to distributed information. caGrid follows a service-oriented model-driven architecture. Each data source in caGrid is associated with metadata at increasing levels of abstraction, including syntactic, structural, reference and domain metadata. The domain metadata consists of ontology-based annotations associated with the structural information of each data source. However, caGrid's current querying functionality is given at the structural metadata level, without capitalising on the ontology-based annotations. This paper presents the design of and theoretical foundations for distributed ontology-based queries over cancer research data. Concept-based queries are reformulated to the target query language, where join conditions between multiple data sources are found by exploiting the semantic annotations. The system has been implemented, as a proof of concept, over the caGrid infrastructure. The approach is applicable to other model-driven architectures. A graphical user interface has been developed, supporting ontology-based queries over caGrid data sources. An extensive evaluation of the query reformulation technique is included. Conclusions To support personalised medicine in oncology, it is crucial to retrieve and integrate molecular, pathology, radiology and clinical data in an efficient manner. The semantic heterogeneity of the data makes this a challenging task. Ontologies provide a formal framework to support querying and integration. This paper provides an ontology-based solution for querying distributed databases over service-oriented, model-driven infrastructures. PMID:22373043

The neurobiology of syntax: beyond string sets.

PubMed

Petersson, Karl Magnus; Hagoort, Peter

2012-07-19

The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty.

The neurobiology of syntax: beyond string sets

PubMed Central

Petersson, Karl Magnus; Hagoort, Peter

2012-01-01

The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty. PMID:22688633

Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet.

PubMed

Mousavi, Seyedeh Neda; Faghihi, Amirhosein; Motaghinejad, Majid; Shiasi, Maryam; Imanparast, Fatemeh; Amiri, Hamid Lorvand; Shidfar, Farzad

2018-02-01

Studies have shown that non-alcoholic fatty liver disease (NAFLD) patients are more prone to cardiovascular disease (CVD). Zinc and selenium deficiency are common in NAFLD. But the effects of zinc and selenium co-supplementation before and/or after disease progression on CVD markers are not clear in NAFLD patients. This study aimed to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on some of the CVD markers in an experimental model of NAFLD. Forty male Sprague Dawley rats (197 ± 4 g) were randomly assigned into four dietary groups: control group (C; received 9% of calorie as fat), model group (M; received 82% of calorie as fat), and supplementation before (BS) or after (AS) disease progression. Animals were fed diets for 20 weeks in all groups. Fasting plasma glucose (FPG), insulin, HOMA-IR, ALT, AST, lipid profile, malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) levels were measured as CVD indices. Serum ALT, AST, FPG, insulin, MDA, VEGF and HOMA-IR were significantly higher in the M than C group. Co-supplementation reduced serum ALT and AST levels in the BS and AS groups compared with the M group. FPG, insulin, HOMA-IR, VEGF, MDA, LDL/HDL-c and TC/HDL-c ratio were significantly reduced in the AS compared with the M group. TG/HDL-c ratio was significantly reduced in the BS and AS compared with the M group. Serum MDA, VEGF, Insulin and HOMA-IR were significantly lowered in the AS than BS group (p < 0.05). Zinc and selenium co-supplementation after NAFLD progression reduced CVD risk indices in an experimental model.

Plant growth modelling and applications: the increasing importance of plant architecture in growth models.

PubMed

Fourcaud, Thierry; Zhang, Xiaopeng; Stokes, Alexia; Lambers, Hans; Körner, Christian

2008-05-01

Modelling plant growth allows us to test hypotheses and carry out virtual experiments concerning plant growth processes that could otherwise take years in field conditions. The visualization of growth simulations allows us to see directly and vividly the outcome of a given model and provides us with an instructive tool useful for agronomists and foresters, as well as for teaching. Functional-structural (FS) plant growth models are nowadays particularly important for integrating biological processes with environmental conditions in 3-D virtual plants, and provide the basis for more advanced research in plant sciences. In this viewpoint paper, we ask the following questions. Are we modelling the correct processes that drive plant growth, and is growth driven mostly by sink or source activity? In current models, is the importance of soil resources (nutrients, water, temperature and their interaction with meristematic activity) considered adequately? Do classic models account for architectural adjustment as well as integrating the fundamental principles of development? Whilst answering these questions with the available data in the literature, we put forward the opinion that plant architecture and sink activity must be pushed to the centre of plant growth models. In natural conditions, sinks will more often drive growth than source activity, because sink activity is often controlled by finite soil resources or developmental constraints. PMA06: This viewpoint paper also serves as an introduction to this Special Issue devoted to plant growth modelling, which includes new research covering areas stretching from cell growth to biomechanics. All papers were presented at the Second International Symposium on Plant Growth Modeling, Simulation, Visualization and Applications (PMA06), held in Beijing, China, from 13-17 November, 2006. Although a large number of papers are devoted to FS models of agricultural and forest crop species, physiological and genetic processes have recently been included and point the way to a new direction in plant modelling research.

Integrating cortico-limbic-basal ganglia architectures for learning model-based and model-free navigation strategies

PubMed Central

Khamassi, Mehdi; Humphries, Mark D.

2012-01-01

Behavior in spatial navigation is often organized into map-based (place-driven) vs. map-free (cue-driven) strategies; behavior in operant conditioning research is often organized into goal-directed vs. habitual strategies. Here we attempt to unify the two. We review one powerful theory for distinct forms of learning during instrumental conditioning, namely model-based (maintaining a representation of the world) and model-free (reacting to immediate stimuli) learning algorithms. We extend these lines of argument to propose an alternative taxonomy for spatial navigation, showing how various previously identified strategies can be distinguished as “model-based” or “model-free” depending on the usage of information and not on the type of information (e.g., cue vs. place). We argue that identifying “model-free” learning with dorsolateral striatum and “model-based” learning with dorsomedial striatum could reconcile numerous conflicting results in the spatial navigation literature. From this perspective, we further propose that the ventral striatum plays key roles in the model-building process. We propose that the core of the ventral striatum is positioned to learn the probability of action selection for every transition between states of the world. We further review suggestions that the ventral striatal core and shell are positioned to act as “critics” contributing to the computation of a reward prediction error for model-free and model-based systems, respectively. PMID:23205006

Experimental study on oral sulfhydryl as an adjuvant for improving nitrate ester tolerance in an animal model.

PubMed

Chen, L; Jiang, J-Q; Zhang, Y; Feng, H

2018-03-01

As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed. After feeding the animals for 5 days, the concentrations of superoxide anion (•O2-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in blood and the relaxation response of the aortic ring were determined in each subject. The vascular plaques in different treatment groups were assessed by Hematoxylin and eosin (HE) staining to investigate the therapeutic value of sulfhydryl as coadjuvant for improving nitrate ester tolerance, and changes in blood vessels in different treatment groups were studied by immunohistochemical assays. Our results showed no significant differences through time in the concentrations of •O2-, SOD, MDA, NO, ET-1 between the healthy control and the nitrate ester groups (p > 0.05). The levels of SOD and MDA in the nitrate ester tolerance group increased with time, however, the levels of •O2-, NO and ET-1 decreased gradually (p < 0.05). The NO, •O2- and ET-1 levels in both the AS and AS + nitrate ester tolerance groups were significantly decreased, but SOD and MDA were significantly increased (p < 0.05). SOD and MDA in the AS + nitrate ester group decreased gradually with time, but •O2-, NO- and ET-1 levels increased (p < 0.05). The levels of SOD and MDA in the AS + drug combination and the drug combination group decreased significantly with time, in contrast, those of •O2-, NO- and ET-1 increased (p < 0.05). The results of HE staining proved that the atherosclerosis model was established successfully. We conclude the use of a sulfhydryl compound as an adjuvant significantly reduced nitrate ester tolerance, and this strategy was safe and looks promising for humans.

The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly

PubMed Central

Bruns, Annie M.; Leser, George P.; Lamb, Robert A.; Horvath, Curt M.

2014-01-01

SUMMARY Cytoplasmic pattern recognition receptors detect non-self RNAs during virus infections and initiate antiviral signaling. One receptor, MDA5, possesses essential signaling domains, but weak RNA binding. A second receptor, LGP2, rapidly detects diverse dsRNA species, but lacks signaling domains. Accumulating evidence suggests LGP2 and MDA5 work together to detect viral RNA and generate a complete antiviral response, but the basis for their cooperation has been elusive. Experiments presented here address this gap in antiviral signaling, revealing that LGP2 assists MDA5-RNA interactions leading to enhanced MDA5-mediated antiviral signaling. LGP2 increases the initial rate of MDA5-RNA interaction and regulates MDA5 filament assembly, resulting in the formation of more numerous, shorter MDA5 filaments that are shown to generate equivalent or greater signaling activity in vivo than the longer filaments containing only MDA5. These findings provide a mechanism for LGP2 co-activation of MDA5 and a biological context for MDA5-RNA filaments in antiviral responses. PMID:25127512

Automation Hooks Architecture for Flexible Test Orchestration - Concept Development and Validation

NASA Technical Reports Server (NTRS)

Lansdowne, C. A.; Maclean, John R.; Winton, Chris; McCartney, Pat

2011-01-01

The Automation Hooks Architecture Trade Study for Flexible Test Orchestration sought a standardized data-driven alternative to conventional automated test programming interfaces. The study recommended composing the interface using multicast DNS (mDNS/SD) service discovery, Representational State Transfer (Restful) Web Services, and Automatic Test Markup Language (ATML). We describe additional efforts to rapidly mature the Automation Hooks Architecture candidate interface definition by validating it in a broad spectrum of applications. These activities have allowed us to further refine our concepts and provide observations directed toward objectives of economy, scalability, versatility, performance, severability, maintainability, scriptability and others.

Algorithms and architecture for multiprocessor based circuit simulation

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

Deutsch, J.T.

Accurate electrical simulation is critical to the design of high performance integrated circuits. Logic simulators can verify function and give first-order timing information. Switch level simulators are more effective at dealing with charge sharing than standard logic simulators, but cannot provide accurate timing information or discover DC problems. Delay estimation techniques and cell level simulation can be used in constrained design methods, but must be tuned for each application, and circuit simulation must still be used to generate the cell models. None of these methods has the guaranteed accuracy that many circuit designers desire, and none can provide detailed waveformmore » information. Detailed electrical-level simulation can predict circuit performance if devices and parasitics are modeled accurately. However, the computational requirements of conventional circuit simulators make it impractical to simulate current large circuits. In this dissertation, the implementation of Iterated Timing Analysis (ITA), a relaxation-based technique for accurate circuit simulation, on a special-purpose multiprocessor is presented. The ITA method is an SOR-Newton, relaxation-based method which uses event-driven analysis and selective trace to exploit the temporal sparsity of the electrical network. Because event-driven selective trace techniques are employed, this algorithm lends itself to implementation on a data-driven computer.« less

Prevention of CCl4-induced liver damage by ginger, garlic and vitamin E.

PubMed

Patrick-Iwuanyanwu, K C; Wegwu, M O; Ayalogu, E O

2007-02-15

The hepatoprotective effects of garlic (Allium sativum), ginger (Zingiber officinale) and vitamin E pre-treatment against carbon tetrachloride (CCl4)-induced liver damage in male wistar albino rats were investigated. Carbon tetrachloride (0.5 mL kg(-1) body weight) was administered after 28 days of feeding animals with diets containing ginger, garlic, vitamin E and various mixtures of ginger and garlic. Serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase levels, 24 h after CCl4 administration, decreased significantly (p < or = 0.05) in rats pre-treated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in CCl4-treated rats only. Lipid peroxidation expressed by serum malondialdehyde (MDA) concentration was assayed to assess the extent of liver damage by CCl4; including the extent of hepatoprotection by garlic, ginger and vitamin E. MDA concentration was significantly decreased (p < or = 0.05) in rats pretreated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in rats administered CCl4-alone. Histological examination of the liver revealed severe infiltration of inflammatory cells in rats treated with CCl4 alone. However, the observed alteration in the normal architecture of the hepatic cells decreased remarkably in pre-treated rats.

Model-Driven Useware Engineering

NASA Astrophysics Data System (ADS)

Meixner, Gerrit; Seissler, Marc; Breiner, Kai

User-oriented hardware and software development relies on a systematic development process based on a comprehensive analysis focusing on the users' requirements and preferences. Such a development process calls for the integration of numerous disciplines, from psychology and ergonomics to computer sciences and mechanical engineering. Hence, a correspondingly interdisciplinary team must be equipped with suitable software tools to allow it to handle the complexity of a multimodal and multi-device user interface development approach. An abstract, model-based development approach seems to be adequate for handling this complexity. This approach comprises different levels of abstraction requiring adequate tool support. Thus, in this chapter, we present the current state of our model-based software tool chain. We introduce the use model as the core model of our model-based process, transformation processes, and a model-based architecture, and we present different software tools that provide support for creating and maintaining the models or performing the necessary model transformations.

Detection of increased 64Cu uptake by human copper transporter 1 gene overexpression using PET with 64CuCl2 in human breast cancer xenograft model.

PubMed

Kim, Kwang Il; Jang, Su Jin; Park, Ju Hui; Lee, Yong Jin; Lee, Tae Sup; Woo, Kwang Sun; Park, Hyun; Choe, Jae Gol; An, Gwang Il; Kang, Joo Hyun

2014-10-01

Copper is an essential cofactor for a variety of biochemical processes including oxidative phosphorylation, cellular antioxidant activity, and elimination of free radicals. The copper transporter 1 is known to be involved in cellular uptake of copper ions. In this study, we evaluated the utility of human copper transporter 1 (hCTR1) gene as a new reporter gene for (64)Cu PET imaging. Human breast cancer cells (MDA-MB-231) were infected with a lentiviral vector constitutively expressing the hCTR1 gene under super cytomegalovirus promoter, and positive clones (MDA-MB-231-hCTR1) were selected. The expression of hCTR1 gene in MDA-MB-231-hCTR1 cells was measured by reverse transcription polymerase chain reaction, Western blot, and (64)Cu uptake assay. To evaluate the cytotoxic effects induced by hCTR1 expression, the dose-dependent cell survival rate after treatment with cisplatin (Cis-diaminedichloroplatinum (II) [CDDP]) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion. Small-animal PET images were acquired in tumor-bearing mice from 2 to 48 h after an intravenous injection of (64)Cu. The hCTR1 gene expression in MDA-MB-231-hCTR1 cells was confirmed at the RNA and protein expression and the cellular (64)Cu uptake level. MTT assay and trypan blue dye exclusion showed that the cell viability of MDA-MB-231-hCTR1 cells decreased more rapidly than that of MDA-MB-231 cells after treatment with CDDP for 96 or 72 h, respectively. Small-animal PET imaging revealed a higher accumulation of (64)Cu in MDA-MB-231-hCTR1 tumors than in MDA-MB-231 tumors. With respect to the biodistribution data, the percentage injected dose per gram of (64)Cu in the MDA-MB-231 tumors and MDA-MB-231-hCTR1 tumors at 48 h after (64)Cu injection was 2.581 ± 0.254 and 5.373 ± 1.098, respectively. An increase in (64)Cu uptake induced by the expression of hCTR1 gene was demonstrated in vivo and in vitro, suggesting the potential use of hCTR1 gene as a new imaging reporter gene for PET with (64)CuCl2. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

[Using the stable HSPA1A promoter-driven luciferase reporter HepG2 cells to assess the overall toxicity of coke oven emissions].

PubMed

Xin, Li-li; Li, Xiao-hai; Deng, Hua-xin; Kuang, Dan; Dai, Xia-yun; Huang, Su-Li; Wang, Feng; He, Mei-an; Currie, R William; Wu, Tang-chun

2012-12-01

Using the stable HSPA1A (HSP70-1) promoter-driven luciferase reporter HepG2 cells (HepG2/HSPA1A cells) to assess the overall toxicity of coke oven emissions. The stable HepG2/HSPA1A cells were treated with different concentrations of coke oven emissions (COEs) collected from the top, side, and bottom of a coke oven battery for 24 h. After the treatments, luciferase activity, cell viability, malondialdehyde (MDA) concentration, Olive tail moment, and micronuclei frequency were determined, respectively. The bottom COEs induced significant increases (P < 0.01) in relative luciferase activity up to 1.4 times the control level at 0.15 µg/L. The low dose of side COEs (0.02 µg/L) led to a significant increase (P < 0.01) in relative luciferase activity that progressively increased to 2.1 times the control level at 65.4 µg/L. The top COEs produced a strong dose-dependent induction of relative luciferase activity up to over 5 times the control level at the highest concentration tested (202 µg/L). In HepG2/HSPA1A cells treated with the bottom COEs, relative luciferase activity was positively correlated with MDA concentration (r = 0.404, P < 0.05). For the three COEs samples, positive correlations were observed between relative luciferase activity and Olive tail moment and micronuclei frequency. The relative luciferase activity in HepG2/HSPA1A cells can sensitively reflect the overall toxicity of COEs. The stable HepG2/HSPA1A cells can be used for rapid screening of the overall toxicity of complex air pollutants in the workplace.

Crosstalk between stromal components and tumor cells of TNBC via secreted factors enhances tumor growth and metastasis

PubMed Central

Jin, Kideok; Pandey, Niranjan B.; Popel, Aleksander S.

2017-01-01

Triple negative breast cancer (TNBC) as a metastatic disease is currently incurable. Reliable and reproducible methods for testing drugs against metastasis are not available. Stromal cells may play a critical role in tumor progression and metastasis. In this study, we determined that fibroblasts and macrophages secreted IL-8 upon induction by tumor cell-conditioned media (TCM) from MDA-MB-231 cancer cells. Our data showed that the proliferation of MDA-MB-231 cells co-cultured with fibroblasts or macrophages was enhanced compared to the monoculture. Furthermore, TNBC cell migration, a key step in tumor metastasis, was promoted by conditioned media (CM) from TCM-induced fibroblasts or macrophages. Knockdown of the IL-8 receptor CXCR2 by CRISPR-Cas9 reduces MDA-MB-231 cell proliferation and migration compared to wild type. In a mouse xenograft tumor model, the growth of MDA-MB-231-CXCR2−/− tumor was significantly decreased compared to the growth of tumors from wild-type cells. In addition, the incidence of thoracic metastasis of MDA-MB-231-CXCR2−/− tumors was reduced compared to wild type. We found that the auto- and paracrine loop exists between TNBC cells and stroma, which results in enhanced IL-8 secretion from the stromal components. Significantly, inhibition of the IL-8 signaling pathway by reparixin, an inhibitor of the IL-8 receptor, CXCR1/2, reduced MDA-MB-231 tumor growth and metastasis. Taken together, these findings implicate IL-8 signaling as a critical event in TNBC tumor growth and metastasis via crosstalk with stromal components. PMID:28947965

Molecular graph convolutions: moving beyond fingerprints

NASA Astrophysics Data System (ADS)

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

Molecular graph convolutions: moving beyond fingerprints.

PubMed

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph-atoms, bonds, distances, etc.-which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

A practical approach for active camera coordination based on a fusion-driven multi-agent system

NASA Astrophysics Data System (ADS)

Bustamante, Alvaro Luis; Molina, José M.; Patricio, Miguel A.

2014-04-01

In this paper, we propose a multi-agent system architecture to manage spatially distributed active (or pan-tilt-zoom) cameras. Traditional video surveillance algorithms are of no use for active cameras, and we have to look at different approaches. Such multi-sensor surveillance systems have to be designed to solve two related problems: data fusion and coordinated sensor-task management. Generally, architectures proposed for the coordinated operation of multiple cameras are based on the centralisation of management decisions at the fusion centre. However, the existence of intelligent sensors capable of decision making brings with it the possibility of conceiving alternative decentralised architectures. This problem is approached by means of a MAS, integrating data fusion as an integral part of the architecture for distributed coordination purposes. This paper presents the MAS architecture and system agents.

Beneficial effects of Aesculus hippocastanum L. seed extract on the body's own antioxidant defense system on subacute administration.

PubMed

Küçükkurt, Ismail; Ince, Sinan; Keleş, Hikmet; Akkol, Esra Küpeli; Avci, Gülcan; Yeşilada, Erdem; Bacak, Elif

2010-05-04

Seeds of Aesculus hippocastanum L. have long been used in European phytotherapy to treat inflammatory and vascular problems. In Turkish folk medicine, tea prepared from the crushed seeds was used to pass kidney stone and against stomach ache, while a fraction of seed was swallowed to alleviate hemorrhoids symptoms. In order to evaluate the in vivo effects of escin mixture from Aesculus hippocastanum seed on the blood and tissue antioxidant defense systems in standard pellet diet (SPD) and in high-fat diet (HFD) consumed male mice. Escin mixture was obtained from the ethanol extract of seeds. Escin mixture was administered orally to male mice fed either standard pellet diet (SPD) or high-fat diet (HFD) at 100mg/kg doses daily for 5 weeks and the tissue (liver, kidney and heart) and blood samples were collected at the end of experimental period. The effect of escin mixture on the plasma antioxidant activity; blood and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels; erythrocyte and tissue superoxide dismutase (SOD) and catalase activity (CAT) in SPD and HFD consumed animals were experimentally studied. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Combined administration of high-fat diet with escin mixture decreased blood (p<0.01), liver (p<0.01), kidney (p<0.05), and heart (p<0.05) of MDA, liver SOD (p<0.01) and CAT (p<0.05) levels and increased blood (p<0.01) and liver GSH (p<0.001) levels in mice. The present results indicate that Aesculus hippocastanum increase the antioxidative defense system of the body and prevent HFD-induced lipid peroxidation in male mice. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Characterization and optimization of the magnetron directional amplifier

NASA Astrophysics Data System (ADS)

Hatfield, Michael Craig

Many applications of microwave wireless power transmission (WPT) are dependent upon a high-powered electronically-steerable phased array composed of many radiating modules. The phase output from the high-gain amplifier in each module must be accurately controlled if the beam is to be properly steered. A highly reliable, rugged, and inexpensive design is essential for making WPT applications practical. A conventional microwave oven magnetron may be combined with a ferrite circulator and other external circuitry to create such a system. By converting it into a two-port amplifier, the magnetron is capable of delivering at least 30 dB of power gain while remaining phase-locked to the input signal over a wide frequency range. The use of the magnetron in this manner is referred to as a MDA (Magnetron Directional Amplifier). The MDA may be integrated with an inexpensive slotted waveguide array (SWA) antenna to form the Electronically-Steerable Phased Array Module (ESPAM). The ESPAM provides a building block approach to creating phased arrays for WPT. The size and shape of the phased array may be tailored to satisfy a diverse range of applications. This study provided an in depth examination into the capabilities of the MDA/ESPAM. The basic behavior of the MDA was already understood, as well as its potential applicability to WPT. The primary objective of this effort was to quantify how well the MDA could perform in this capacity. Subordinate tasks included characterizing the MDA behavior in terms of its system inputs, optimizing its performance, performing sensitivity analyses, and identifying operating limitations. A secondary portion of this study examined the suitability of the ESPAM in satisfying system requirements for the solar power satellite (SPS). Supporting tasks included an analysis of SPS requirements, modeling of the SWA antenna, and the demonstration of a simplified phased array constructed of ESPAM elements. The MDA/ESPAM is well suited for use as an amplifier or an element in a WPT phased array, providing over 75% efficiency and a fractional bandwidth exceeding 1.7% at 2.45 GHz. The results of this effort provide the WPT design engineer with tools to predict the MDA's optimum performance and limitations.

[Research on improving memory impairment of blue lavender volatile oil].

PubMed

Zhu, Li-Yun; Gao, Yong-Sheng; Song, Lin-Zhen; Li, Su-Fang; Qian, Jun-Qing

2017-12-01

In order to study the potential application value of lavender volatile oil (LVO), the chemical composition of the volatile oil of lavender was analyzed by GC-MS, and the mouse model of Alzheimer's disease (AD) was established. Additionally, the antioxidant enzymes activity of T-SOD, GSH-PX, CAT and MDA content were studied. Experimental results showed that 55 kinds of chemical constituents including terpene, terpene alcohol and ester compounds from LVO were identified, and the content of linalool and linalyl acetate was the highest, accounting for 49.71% of the total volatile oil. The ability of mouse platform memory was improved significantly. The levels of GSH-PX, CAT and T-SOD of mouse brain tissue in the treatment group were significantly higher than those in the model group (P<0.05). The level of MDA reached the maximum value in the model group, while there was no notable difference between the levels of MDA in the drug group and the normal group. The result indicated the significant oxidative activity of LVO, the possibility of induced oxidative stress reduction in neurons, and the reversal effect of memory acquired disorder. Copyright© by the Chinese Pharmaceutical Association.

A Demand-Driven Approach for a Multi-Agent System in Supply Chain Management

NASA Astrophysics Data System (ADS)

Kovalchuk, Yevgeniya; Fasli, Maria

This paper presents the architecture of a multi-agent decision support system for Supply Chain Management (SCM) which has been designed to compete in the TAC SCM game. The behaviour of the system is demand-driven and the agents plan, predict, and react dynamically to changes in the market. The main strength of the system lies in the ability of the Demand agent to predict customer winning bid prices - the highest prices the agent can offer customers and still obtain their orders. This paper investigates the effect of the ability to predict customer order prices on the overall performance of the system. Four strategies are proposed and compared for predicting such prices. The experimental results reveal which strategies are better and show that there is a correlation between the accuracy of the models' predictions and the overall system performance: the more accurate the prediction of customer order prices, the higher the profit.

Metadata-Driven SOA-Based Application for Facilitation of Real-Time Data Warehousing

NASA Astrophysics Data System (ADS)

Pintar, Damir; Vranić, Mihaela; Skočir, Zoran

Service-oriented architecture (SOA) has already been widely recognized as an effective paradigm for achieving integration of diverse information systems. SOA-based applications can cross boundaries of platforms, operation systems and proprietary data standards, commonly through the usage of Web Services technology. On the other side, metadata is also commonly referred to as a potential integration tool given the fact that standardized metadata objects can provide useful information about specifics of unknown information systems with which one has interest in communicating with, using an approach commonly called "model-based integration". This paper presents the result of research regarding possible synergy between those two integration facilitators. This is accomplished with a vertical example of a metadata-driven SOA-based business process that provides ETL (Extraction, Transformation and Loading) and metadata services to a data warehousing system in need of a real-time ETL support.

Real-time computing platform for spiking neurons (RT-spike).

PubMed

Ros, Eduardo; Ortigosa, Eva M; Agís, Rodrigo; Carrillo, Richard; Arnold, Michael

2006-07-01

A computing platform is described for simulating arbitrary networks of spiking neurons in real time. A hybrid computing scheme is adopted that uses both software and hardware components to manage the tradeoff between flexibility and computational power; the neuron model is implemented in hardware and the network model and the learning are implemented in software. The incremental transition of the software components into hardware is supported. We focus on a spike response model (SRM) for a neuron where the synapses are modeled as input-driven conductances. The temporal dynamics of the synaptic integration process are modeled with a synaptic time constant that results in a gradual injection of charge. This type of model is computationally expensive and is not easily amenable to existing software-based event-driven approaches. As an alternative we have designed an efficient time-based computing architecture in hardware, where the different stages of the neuron model are processed in parallel. Further improvements occur by computing multiple neurons in parallel using multiple processing units. This design is tested using reconfigurable hardware and its scalability and performance evaluated. Our overall goal is to investigate biologically realistic models for the real-time control of robots operating within closed action-perception loops, and so we evaluate the performance of the system on simulating a model of the cerebellum where the emulation of the temporal dynamics of the synaptic integration process is important.

Integration of Enzymes in Polyaniline-Sensitized 3D Inverse Opal TiO2 Architectures for Light-Driven Biocatalysis and Light-to-Current Conversion.

PubMed

Riedel, Marc; Lisdat, Fred

2018-01-10

Inspired by natural photosynthesis, coupling of artificial light-sensitive entities with biocatalysts in a biohybrid format can result in advanced photobioelectronic systems. Herein, we report on the integration of sulfonated polyanilines (PMSA1) and PQQ-dependent glucose dehydrogenase (PQQ-GDH) into inverse opal TiO 2 (IO-TiO 2 ) electrodes. While PMSA1 introduces sensitivity for visible light into the biohybrid architecture and ensures the efficient wiring between the IO-TiO 2 electrode and the biocatalytic entity, PQQ-GDH provides the catalytic activity for the glucose oxidation and therefore feeds the light-driven reaction with electrons for an enhanced light-to-current conversion. Here, the IO-TiO 2 electrodes with pores of around 650 nm provide a suitable interface and morphology needed for the stable and functional assembly of polymer and enzyme. The IO-TiO 2 electrodes have been prepared by a template approach applying spin coating, allowing an easy scalability of the electrode height and surface area. The successful integration of the polymer and the enzyme is confirmed by the generation of an anodic photocurrent, showing an enhanced magnitude with increasing glucose concentrations. Compared to flat and nanostructured TiO 2 electrodes, the three-layered IO-TiO 2 electrodes give access to a 24-fold and 29-fold higher glucose-dependent photocurrent due to the higher polymer and enzyme loading in IO films. The three-dimensional IO-TiO 2 |PMSA1|PQQ-GDH architecture reaches maximum photocurrent densities of 44.7 ± 6.5 μA cm -2 at low potentials in the presence of glucose (for a three TiO 2 layer arrangement). The onset potential for the light-driven substrate oxidation is found to be at -0.315 V vs Ag/AgCl (1 M KCl) under illumination with 100 mW cm -2 , which is more negative than the redox potential of the enzyme. The results demonstrate the advantageous properties of IO-TiO 2 |PMSA1|PQQ-GDH biohybrid architectures for the light-driven glucose conversion with improved performance.

Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells Through Modulation of the Phosphatidylinositol 3-Kinase Pathway

PubMed Central

Adams, Lynn S.; Phung, Sheryl; Yee, Natalie; Seeram, Navindra P.; Li, Liya; Chen, Shiuan

2010-01-01

Dietary phytochemicals are known to exhibit a variety of anti-carcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple negative breast cancer cell lines in vitro and in vivo. Blueberry decreased cell proliferation in HCC38, HCC1937 and MDA-MB-231 cells with no effect on the non-tumorigenic MCF-10A cell line. Decreased metastatic potential of MDA-MB-231 cells by blueberry was shown through inhibition of cell motility using wound healing assays and migration through a PET membrane. Blueberry treatment decreased the activity of matrix metalloproteinase 9 and the secretion of urokinase-type plasminogen activator while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion in MDA-MB-231 conditioned medium as shown by western blotting. Cell signaling pathways that control the expression/activation of these processes were investigated via western blotting and reporter gene assay. Treatment with blueberry decreased phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor kappa-B (NFκB) activation in MDA-MB-231 cells where protein kinase C (PKC) and extracellular regulated kinase (ERK) were not affected. In vivo, the efficacy of blueberry to inhibit triple negative breast tumor growth was evaluated using the MDA-MB-231 xenograft model. Tumor weight and proliferation (Ki-67 expression) were decreased in blueberry treated mice, where apoptosis (caspase-3 expression) was increased compared to controls. Immunohistochemical analysis of tumors from blueberry-fed mice showed decreased activation of AKT and p65 NFκB signaling proteins with no effect on the phosphorylation of ERK. These data illustrate the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cells through modulation of the PI3K/AKT/NFκB pathway. PMID:20388778

Archetype Model-Driven Development Framework for EHR Web System.

PubMed

Kobayashi, Shinji; Kimura, Eizen; Ishihara, Ken

2013-12-01

This article describes the Web application framework for Electronic Health Records (EHRs) we have developed to reduce construction costs for EHR sytems. The openEHR project has developed clinical model driven architecture for future-proof interoperable EHR systems. This project provides the specifications to standardize clinical domain model implementations, upon which the ISO/CEN 13606 standards are based. The reference implementation has been formally described in Eiffel. Moreover C# and Java implementations have been developed as reference. While scripting languages had been more popular because of their higher efficiency and faster development in recent years, they had not been involved in the openEHR implementations. From 2007, we have used the Ruby language and Ruby on Rails (RoR) as an agile development platform to implement EHR systems, which is in conformity with the openEHR specifications. We implemented almost all of the specifications, the Archetype Definition Language parser, and RoR scaffold generator from archetype. Although some problems have emerged, most of them have been resolved. We have provided an agile EHR Web framework, which can build up Web systems from archetype models using RoR. The feasibility of the archetype model to provide semantic interoperability of EHRs has been demonstrated and we have verified that that it is suitable for the construction of EHR systems.

Post-fertilization effect of bilateral primary testicular damage induced by unilateral cryptorchidism in the rat model.

PubMed

Tsounapi, P; Honda, M; Dimitriadis, F; Shimizu, S; Hikita, K; Muraoka, K; Sejima, T; Saito, M; Tomita, S; Sofikitis, N; Takenaka, A

2016-03-01

Cryptorchidism, a common anomaly of the male genitalia, affects 2-4% of male infants. The post-fertilization effects of unilateral cryptorchidism model in the rat and the effects of antioxidant treatment were investigated. Six-week-old male Wistar rats were randomly separated into four groups. Unilateral cryptorchidism was induced in the right testis of three groups. One group was treated with saline intraperitoneally (i.p.) (Crypto), one group was treated with taurine (500 mg/kg, i.p.; Tau), and another group was treated with sivelestat (15 mg/kg i.p.; Siv). The control group was treated with saline i.p. The treatment was daily for 8 weeks. Five days before sacrifice, mating studies were performed. Body, testicular, and epididymal weights were recorded. Malondialdehyde (MDA) levels in the seminal vesicular fluid (SVF) were measured. Testicular levels of MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined bilaterally. TUNEL assay was used to examine DNA fragmentation bilaterally. Histological examination and the Johnsen score were used to evaluate morphological testicular alterations. The Crypto group demonstrated significantly lower right testicular and epididymal weights, significantly increased SVF-MDA levels, testicular MDA and 8-OHdG levels, and the apoptotic score bilaterally compared to the controls. Furthermore, histological evaluation revealed significantly reduced spermatogenesis and mild injury to the cryptorchid testes compared to the control. Treatment with both taurine and sivelestat significantly reduced SVF-MDA levels, testicular MDA, 8-OHdG, and apoptosis bilaterally compared to the Crypto group. Antioxidant treatment was unable to ameliorate spermatogenesis. Newborns delivered by females that mated with Crypto-males had significantly lower body weight compared with the respective animals from the control, Tau and Siv groups. The present study demonstrated that unilateral cryptorchidism-induced testicular damage can significantly affect the contralateral testis as well having further deleterious post-fertilization effect on the development of newborns. Treatment with antioxidants can partially improve the testicular damage bilaterally with beneficial effects for the newborns. © 2016 American Society of Andrology and European Academy of Andrology.

Human Breast Cancer Histoid

PubMed Central

Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

2011-01-01

Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

Retrosynthetic Reaction Prediction Using Neural Sequence-to-Sequence Models

PubMed Central

2017-01-01

We describe a fully data driven model that learns to perform a retrosynthetic reaction prediction task, which is treated as a sequence-to-sequence mapping problem. The end-to-end trained model has an encoder–decoder architecture that consists of two recurrent neural networks, which has previously shown great success in solving other sequence-to-sequence prediction tasks such as machine translation. The model is trained on 50,000 experimental reaction examples from the United States patent literature, which span 10 broad reaction types that are commonly used by medicinal chemists. We find that our model performs comparably with a rule-based expert system baseline model, and also overcomes certain limitations associated with rule-based expert systems and with any machine learning approach that contains a rule-based expert system component. Our model provides an important first step toward solving the challenging problem of computational retrosynthetic analysis. PMID:29104927

Estrogen and the Dietary Phytoestrogen Tesveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Research

DTIC Science & Technology

2008-06-01

neuroblastoma SH - SY5Y cells . Neurosci.Lett. 1999;264:141- 4. 18. Pozo-Guisado E, Alvarez-Barrientos A, Mulero-Navarro S, Santiago-Josefat B, Fernandez...inhibitor on breast cancer invasion and metastasis using human breast cancer cell lines and a nude mouse model. The following are our Specific Aims...MDA-MB-231 and MDA-MB-435 human breast cancer cell lines will be treated with vehicle control, resveratrol, E2, or Rac-specific inhibitor NSC23766 and

Targeting Therapy Resistant Tumor Vessels

DTIC Science & Technology

2008-08-01

No 6 C8161 s.c. xenografts No 5 K14-HPV16 skin cancer No 4 MDA-MB-435 orthotopic xenografts No 4 AGR TRAMP PIN lesions TRAMP PIN lesions Yes 18 TRAMP...CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c...Summary We developed three tumor models under this project: 4T1 mouse breast cancer and MDA-MB-435 human cancer xenograft tumors treated with anti

Nanomechanical architecture of semiconductor nanomembranes.

PubMed

Huang, Minghuang; Cavallo, Francesca; Liu, Feng; Lagally, Max G

2011-01-01

Semiconductor nanomembranes are single-crystal sheets with thickness ranging from 5 to 500nm. They are flexible, bondable, and mechanically ultra-compliant. They present a new platform to combine bottom-up and top-down semiconductor processing to fabricate various three-dimensional (3D) nanomechanical architectures, with an unprecedented level of control. The bottom-up part is the self-assembly, via folding, rolling, bending, curling, or other forms of shape change of the nanomembranes, with top-down patterning providing the starting point for these processes. The self-assembly to form 3D structures is driven by elastic strain relaxation. A variety of structures, including tubes, rings, coils, rolled-up "rugs", and periodic wrinkles, has been made by such self-assembly. Their geometry and unique properties suggest many potential applications. In this review, we describe the design of desired nanostructures based on continuum mechanics modelling, definition and fabrication of 2D strained nanomembranes according to the established design, and release of the 2D strained sheet into a 3D or quasi-3D object. We also describe several materials properties of nanomechanical architectures. We discuss potential applications of nanomembrane technology to implement simple and hybrid functionalities.

Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

PubMed

Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R; Ingram, Marylou; Imam, S Ashraf

2011-12-01

Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.

Concept of operations for knowledge discovery from Big Data across enterprise data warehouses

NASA Astrophysics Data System (ADS)

Sukumar, Sreenivas R.; Olama, Mohammed M.; McNair, Allen W.; Nutaro, James J.

2013-05-01

The success of data-driven business in government, science, and private industry is driving the need for seamless integration of intra and inter-enterprise data sources to extract knowledge nuggets in the form of correlations, trends, patterns and behaviors previously not discovered due to physical and logical separation of datasets. Today, as volume, velocity, variety and complexity of enterprise data keeps increasing, the next generation analysts are facing several challenges in the knowledge extraction process. Towards addressing these challenges, data-driven organizations that rely on the success of their analysts have to make investment decisions for sustainable data/information systems and knowledge discovery. Options that organizations are considering are newer storage/analysis architectures, better analysis machines, redesigned analysis algorithms, collaborative knowledge management tools, and query builders amongst many others. In this paper, we present a concept of operations for enabling knowledge discovery that data-driven organizations can leverage towards making their investment decisions. We base our recommendations on the experience gained from integrating multi-agency enterprise data warehouses at the Oak Ridge National Laboratory to design the foundation of future knowledge nurturing data-system architectures.

[Effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats].

PubMed

Wang, Shixiang; Lu, Zhifeng; Xu, Wei; Chen, Youquan; Chen, Ximing

2015-11-01

To investigate the effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats. Fifty male SD rats were randomly divided into 5 groups, including a control group, a myocardial fibrosis model (established by injections of isopropyl adrenaline for 10 days) group, and 3 edaravone groups with edaravone treatment at low, medium, or high doses for 14 days. After the treatments, the rats were examined for the degree of myocardial fibrosis, left ventricular mass index (LVMI), collagen volume fraction (CVF), and myocardial contents of collagen I (Col I), collage III (Col III), hydroxyproline (Hyp), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO); The expression of transforming growth factor-β1 (TGF-β1) in the myocardial tissues was examined by immunofluorescence assay and Western blotting. Compared with the control rats, the rat models of myocardial fibrosis showed significantly increased CVF and LVMI (P=0.000), which were lowered by edaravone treatments in a dose-dependent manner (P<0.05). The myocardial contents of Col I, Col III and Hyp also increased in the model group (P=0.000) and were lowered dose-dependently by edaravone; the contents of MDA was higher (P=0.000) and SOD and NO were lower in the model group (P=0.000), and edaravone treatments obviously increased SOD and NO contents (P<0.05). The model rats showed significantly increased myocardial expression of TGF-β1 (P=0.000), which was markedly lowered by edaravone treatments (P=0.000). The myocardial content of MDA was positively correlated while SOD and NO were negatively with LVMI, CVF, Col I, Col III and Hyp; TGF-β1 was positively correlated with LVMI, CVF, Col I, Col III, Hyp and MDA but negatively with SOD and NO. Edaravone can relieve oxidative stress and inhibit TGF-β1 activation to ameliorate myocardial fibrosis in rats.

Achieving High Performance With TCP Over 40 GbE on NUMA Architectures for CMS Data Acquisition

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

Bawej, Tomasz; et al.

2014-01-01

TCP and the socket abstraction have barely changed over the last two decades, but at the network layer there has been a giant leap from a few megabits to 100 gigabits in bandwidth. At the same time, CPU architectures have evolved into the multicore era and applications are expected to make full use of all available resources. Applications in the data acquisition domain based on the standard socket library running in a Non-Uniform Memory Access (NUMA) architecture are unable to reach full efficiency and scalability without the software being adequately aware about the IRQ (Interrupt Request), CPU and memory affinities.more » During the first long shutdown of LHC, the CMS DAQ system is going to be upgraded for operation from 2015 onwards and a new software component has been designed and developed in the CMS online framework for transferring data with sockets. This software attempts to wrap the low-level socket library to ease higher-level programming with an API based on an asynchronous event driven model similar to the DAT uDAPL API. It is an event-based application with NUMA optimizations, that allows for a high throughput of data across a large distributed system. This paper describes the architecture, the technologies involved and the performance measurements of the software in the context of the CMS distributed event building.« less

Space Launch System Ascent Flight Control Design

NASA Technical Reports Server (NTRS)

VanZwieten, Tannen S.; Orr, Jeb S.; Wall, John H.; Hall, Charles E.

2014-01-01

A robust and flexible autopilot architecture for NASA's Space Launch System (SLS) family of launch vehicles is presented. As the SLS configurations represent a potentially significant increase in complexity and performance capability of the integrated flight vehicle, it was recognized early in the program that a new, generalized autopilot design should be formulated to fulfill the needs of this new space launch architecture. The present design concept is intended to leverage existing NASA and industry launch vehicle design experience and maintain the extensibility and modularity necessary to accommodate multiple vehicle configurations while relying on proven and flight-tested control design principles for large boost vehicles. The SLS flight control architecture combines a digital three-axis autopilot with traditional bending filters to support robust active or passive stabilization of the vehicle's bending and sloshing dynamics using optimally blended measurements from multiple rate gyros on the vehicle structure. The algorithm also relies on a pseudo-optimal control allocation scheme to maximize the performance capability of multiple vectored engines while accommodating throttling and engine failure contingencies in real time with negligible impact to stability characteristics. The architecture supports active in-flight load relief through the use of a nonlinear observer driven by acceleration measurements, and envelope expansion and robustness enhancement is obtained through the use of a multiplicative forward gain modulation law based upon a simple model reference adaptive control scheme.

Space Launch System Ascent Flight Control Design

NASA Technical Reports Server (NTRS)

Orr, Jeb S.; Wall, John H.; VanZwieten, Tannen S.; Hall, Charles E.

2014-01-01

A robust and flexible autopilot architecture for NASA's Space Launch System (SLS) family of launch vehicles is presented. The SLS configurations represent a potentially significant increase in complexity and performance capability when compared with other manned launch vehicles. It was recognized early in the program that a new, generalized autopilot design should be formulated to fulfill the needs of this new space launch architecture. The present design concept is intended to leverage existing NASA and industry launch vehicle design experience and maintain the extensibility and modularity necessary to accommodate multiple vehicle configurations while relying on proven and flight-tested control design principles for large boost vehicles. The SLS flight control architecture combines a digital three-axis autopilot with traditional bending filters to support robust active or passive stabilization of the vehicle's bending and sloshing dynamics using optimally blended measurements from multiple rate gyros on the vehicle structure. The algorithm also relies on a pseudo-optimal control allocation scheme to maximize the performance capability of multiple vectored engines while accommodating throttling and engine failure contingencies in real time with negligible impact to stability characteristics. The architecture supports active in-flight disturbance compensation through the use of nonlinear observers driven by acceleration measurements. Envelope expansion and robustness enhancement is obtained through the use of a multiplicative forward gain modulation law based upon a simple model reference adaptive control scheme.

Enhanced situational awareness in the maritime domain: an agent-based approach for situation management

NASA Astrophysics Data System (ADS)

Brax, Christoffer; Niklasson, Lars

2009-05-01

Maritime Domain Awareness is important for both civilian and military applications. An important part of MDA is detection of unusual vessel activities such as piracy, smuggling, poaching, collisions, etc. Today's interconnected sensorsystems provide us with huge amounts of information over large geographical areas which can make the operators reach their cognitive capacity and start to miss important events. We propose and agent-based situation management system that automatically analyse sensor information to detect unusual activity and anomalies. The system combines knowledge-based detection with data-driven anomaly detection. The system is evaluated using information from both radar and AIS sensors.

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone.

PubMed

Aregawi, Maru; Smith, Samuel J; Sillah-Kanu, Musa; Seppeh, John; Kamara, Anitta R Y; Williams, Ryan O; Aponte, John J; Bosman, Andrea; Alonso, Pedro

2016-09-20

As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate-amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014-January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38-48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41-52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32-38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39-52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29-38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13-46 %) at week 1 post-first MDA and much lower during all the weeks post-second MDA. The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.

Markers of Oxidative Status in a Clinical Model of Oxidative Assault: a Pilot Study in Human Blood Following Doxorubicin Administration

PubMed Central

Il'yasova, Dora; Mixon, Gabriel; Wang, Frances; Marcom, P Kelly; Marks, Jeffrey; Spasojevich, Ivan; Craft, Neal; Arredondo, Francisco; DiGiulio, Richard

2009-01-01

We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and α- and γ-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt). In all subjects, PPCC and MDA levels did not change. erGSHt levels increased at T24 by 8% (p=0.03). Levels of α, γ, and total tocopherols progressively decreased by 7%−15% (P<0.05). In subjects with low erGSHt levels (below median), PPCC mean levels progressively increased from 0.35 (T0) to 0.56 (T1) and 0.72 nmol carbonyl/mg protein (T24) (p=0.2). These results indicate that (1) plasma MDA is not a sensitive biomarker in humans; (2) PPCC potentially may be used, if antioxidant reserves are taken into account; (3) antioxidant reserves play an important role in the reaction to oxidative stress. PMID:19476408

P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment

PubMed Central

Joo, Young Nak; Jin, Hana; Eun, So Young; Park, Sang Won; Chang, Ki Churl; Kim, Hye Jung

2014-01-01

Tumor microenvironmental hypoxia induces hypoxia inducible factor-1α (HIF-1α) overexpression, leading to the release of lysyl oxidase (LOX), which crosslinks collagen at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Our previous study showed that activation of the P2Y2 receptor (P2Y2R) by ATP released from MDA-MB-231 cells increased MDA-MB-231 cell invasion through endothelial cells. Therefore, in this study, we investigated the role of P2Y2R in breast cancer cell metastasis to distant sites. ATP or UTP released from hypoxia-treated MDA-MB-231 cells induced HIF-1α expression and LOX secretion by the activation of P2Y2R, and this phenomenon was significantly reduced in P2Y2R-depleted MDA-MB-231 cells. Furthermore, P2Y2R-mediated LOX release induced collagen crosslinking in an in vitro model. Finally, nude mice injected with MDA-MB-231 cells showed high levels of LOX secretion, crosslinked collagen and CD11b+ BMDC recruitment in the lung; however, mice that were injected with P2Y2R-depleted MDA-MB-231 cells did not exhibit these changes. These results demonstrate that P2Y2R plays an important role in activation of the HIF-1α–LOX axis, the induction of collagen crosslinking and the recruitment of CD11b+ BMDCs. Furthermore, P2Y2R activation by nucleotides recruits THP-1 monocytes, resulting in primary tumor progression and pre-metastatic niche formation. PMID:25238333

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

PubMed

Lo, Nathan C; Gurarie, David; Yoon, Nara; Coulibaly, Jean T; Bendavid, Eran; Andrews, Jason R; King, Charles H

2018-01-23

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA. Copyright © 2018 the Author(s). Published by PNAS.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis

PubMed Central

Yoon, Nara; Coulibaly, Jean T.; Bendavid, Eran; Andrews, Jason R.; King, Charles H.

2018-01-01

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5–20%) and high-prevalence (25–50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, “hot spots” of transmission, and noncompliance to MDA. PMID:29301964

A computer architecture for intelligent machines

NASA Technical Reports Server (NTRS)

Lefebvre, D. R.; Saridis, G. N.

1991-01-01

The Theory of Intelligent Machines proposes a hierarchical organization for the functions of an autonomous robot based on the Principle of Increasing Precision With Decreasing Intelligence. An analytic formulation of this theory using information-theoretic measures of uncertainty for each level of the intelligent machine has been developed in recent years. A computer architecture that implements the lower two levels of the intelligent machine is presented. The architecture supports an event-driven programming paradigm that is independent of the underlying computer architecture and operating system. Details of Execution Level controllers for motion and vision systems are addressed, as well as the Petri net transducer software used to implement Coordination Level functions. Extensions to UNIX and VxWorks operating systems which enable the development of a heterogeneous, distributed application are described. A case study illustrates how this computer architecture integrates real-time and higher-level control of manipulator and vision systems.

Solvable Family of Driven-Dissipative Many-Body Systems.

PubMed

Foss-Feig, Michael; Young, Jeremy T; Albert, Victor V; Gorshkov, Alexey V; Maghrebi, Mohammad F

2017-11-10

Exactly solvable models have played an important role in establishing the sophisticated modern understanding of equilibrium many-body physics. Conversely, the relative scarcity of solutions for nonequilibrium models greatly limits our understanding of systems away from thermal equilibrium. We study a family of nonequilibrium models, some of which can be viewed as dissipative analogues of the transverse-field Ising model, in that an effectively classical Hamiltonian is frustrated by dissipative processes that drive the system toward states that do not commute with the Hamiltonian. Surprisingly, a broad and experimentally relevant subset of these models can be solved efficiently. We leverage these solutions to compute the effects of decoherence on a canonical trapped-ion-based quantum computation architecture, and to prove a no-go theorem on steady-state phase transitions in a many-body model that can be realized naturally with Rydberg atoms or trapped ions.

Solvable Family of Driven-Dissipative Many-Body Systems

NASA Astrophysics Data System (ADS)

Foss-Feig, Michael; Young, Jeremy T.; Albert, Victor V.; Gorshkov, Alexey V.; Maghrebi, Mohammad F.

2017-11-01

Exactly solvable models have played an important role in establishing the sophisticated modern understanding of equilibrium many-body physics. Conversely, the relative scarcity of solutions for nonequilibrium models greatly limits our understanding of systems away from thermal equilibrium. We study a family of nonequilibrium models, some of which can be viewed as dissipative analogues of the transverse-field Ising model, in that an effectively classical Hamiltonian is frustrated by dissipative processes that drive the system toward states that do not commute with the Hamiltonian. Surprisingly, a broad and experimentally relevant subset of these models can be solved efficiently. We leverage these solutions to compute the effects of decoherence on a canonical trapped-ion-based quantum computation architecture, and to prove a no-go theorem on steady-state phase transitions in a many-body model that can be realized naturally with Rydberg atoms or trapped ions.

Development of modified MDA (M-MDA), PWR fuel cladding tube for high duty operation in future

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

Watanabe, Seiichi; Kido, Toshiya; Arakawa, Yasushi

2007-07-01

A new cladding material of M-MDA has been developed in order to prepare for a strong growing demand for advanced fuel which can maintain its integrity even under high duties due to more efficient operation such as higher burnup, higher LHR, and longer operation cycle which will contribute the suppression of environmental burdens like CO{sub 2} emission. The main aim of M-MDA is to have excellent corrosion resistance while the other properties are inherited from MDA, which has been adopted to the step 2 fuel, instead of Zry-4, of Japanese PWR plant whose upper limit of assembly discharged burnup ismore » 55 MWd/kgU. And we could confirm that the main aim of M-MDA was achieved by means of out-of-pile tests. In order to confirm improvement of corrosion resistance of M-MDA in the actual operation, irradiation test of M-MDA in the commercial reactor of Vandellos II is ongoing. The latest results of on-site examination after every end of cycle showed that oxide thickness of M-MDA-SR was much smaller than that of MDA at rod discharged burnup of approximately 60 MWd/kgU. The final irradiation cycle was completed on April 2007 and then we will obtain corrosion data of M-MDA over 70 MWd/kgU. M-MDA is a candidate alloy for advanced fuel under higher duty usage. (authors)« less

Sensor fusion IV: Control paradigms and data structures; Proceedings of the Meeting, Boston, MA, Nov. 12-15, 1991

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1992-01-01

Various papers on control paradigms and data structures in sensor fusion are presented. The general topics addressed include: decision models and computational methods, sensor modeling and data representation, active sensing strategies, geometric planning and visualization, task-driven sensing, motion analysis, models motivated biology and psychology, decentralized detection and distributed decision, data fusion architectures, robust estimation of shapes and features, application and implementation. Some of the individual subjects considered are: the Firefly experiment on neural networks for distributed sensor data fusion, manifold traversing as a model for learning control of autonomous robots, choice of coordinate systems for multiple sensor fusion, continuous motion using task-directed stereo vision, interactive and cooperative sensing and control for advanced teleoperation, knowledge-based imaging for terrain analysis, physical and digital simulations for IVA robotics.

Community Attitudes toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases after the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia

PubMed Central

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J.; Fischer, Peter U.; Kollie, Karsor; Bolay, Fatorma K.

2016-01-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. PMID:26666700

Recurrent rhinovirus infections in a child with inherited MDA5 deficiency

PubMed Central

Lamborn, Ian T.; Jing, Huie; Zhang, Yu; Munir, Shirin; Bade, Sangeeta; Murdock, Heardley M.; Santos, Celia P.; Brock, Linda G.; Masutani, Evan; Matthews, Helen F.; Collins, Peter L.; Subbarao, Kanta; Gelfand, Erwin W.

2017-01-01

MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs. In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ. However, wild-type MDA5 did not restrict influenza virus or RSV replication. Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV. Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus. PMID:28606988

The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

PubMed

El-Deeb, Wael M; Buczinski, Sébastien

2015-01-01

The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

CLARA: CLAS12 Reconstruction and Analysis Framework

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

Gyurjyan, Vardan; Matta, Sebastian Mancilla; Oyarzun, Ricardo

2016-11-01

In this paper we present SOA based CLAS12 event Reconstruction and Analyses (CLARA) framework. CLARA design focus is on two main traits: real-time data stream processing, and service-oriented architecture (SOA) in a flow based programming (FBP) paradigm. Data driven and data centric architecture of CLARA presents an environment for developing agile, elastic, multilingual data processing applications. The CLARA framework presents solutions capable of processing large volumes of data interactively and substantially faster than batch systems.

Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

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

Kumar, Vijay; Kalita, Jayantee, E-mail: jayanteek@yahoo.com; Bora, Himangsu K.

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the endmore » of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO{sub 4} resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration. - Highlights: • Oral dosing of CuSO{sub 4} leads to oxidative stress in liver, brain and kidney. • Liver has maximum oxidative stress followed by brain and kidney. • Oxidative stress correlated with the respective organ dysfunction and tissue Cu concentration.« less

Dermal uptake and excretion of 4,4'-methylenedianiline during rotor blade production in helicopter industry--an intervention study.

PubMed

Weiss, Tobias; Schuster, Hubert; Müller, Johannes; Schaller, Karl-Heinz; Drexler, Hans; Angerer, Jürgen; Käfferlein, Heiko U

2011-10-01

Workers using composite materials by fibre reinforced laminate technology are exposed to 4,4'-methylenedianiline (MDA), a liver toxicant and suspected human carcinogen, during the production of rotor blades in helicopter industry. The aim of the study presented here was to assess the internal dose of MDA and the suitability of various personal protection measures at the workplace. Ambient monitoring and biological monitoring was carried out by analysing MDA in air and urine samples in seven workers of a highly specialized workplace (rotor blade production). Three different concepts of personal protection measures were applied to study the route of uptake and to evaluate strategies in decreasing workplace exposure. In addition, elimination kinetics of MDA was studied in three workers who were exposed to MDA on three consecutive working days. Ambient monitoring consistently provided air levels at or below the limit of quantification of 0.1 μg m(-3). Nevertheless, MDA was detected in 89% of all post-shift urine samples and median concentration was 4.2 μg l(-1). MDA in urine were >20 times higher than expected on data from ambient monitoring alone. A significant decrease in exposure could be achieved when workers have worn MDA-protective overalls in combination with MDA-protective gloves and a splash protection shield (from 9.8 μg l(-1) down to 3.7 μg l(-1)). The results show that MDA is taken up primarily via the skin at the workplaces under study. The excretion of MDA in urine was observed to be delayed after dermal exposure. Exposure assessment of MDA should be carried out by biological monitoring rather than ambient monitoring. For this purpose, urine samples midweek or at the end of the week should be used based on the observed delay in the excretion of MDA after dermal absorption. Uptake of MDA via the skin could not be completely avoided even if state-of-the-art personal protection measures were applied.

Wavy Architecture Thin-Film Transistor for Ultrahigh Resolution Flexible Displays.

PubMed

Hanna, Amir Nabil; Kutbee, Arwa Talal; Subedi, Ram Chandra; Ooi, Boon; Hussain, Muhammad Mustafa

2018-01-01

A novel wavy-shaped thin-film-transistor (TFT) architecture, capable of achieving 70% higher drive current per unit chip area when compared with planar conventional TFT architectures, is reported for flexible display application. The transistor, due to its atypical architecture, does not alter the turn-on voltage or the OFF current values, leading to higher performance without compromising static power consumption. The concept behind this architecture is expanding the transistor's width vertically through grooved trenches in a structural layer deposited on a flexible substrate. Operation of zinc oxide (ZnO)-based TFTs is shown down to a bending radius of 5 mm with no degradation in the electrical performance or cracks in the gate stack. Finally, flexible low-power LEDs driven by the respective currents of the novel wavy, and conventional coplanar architectures are demonstrated, where the novel architecture is able to drive the LED at 2 × the output power, 3 versus 1.5 mW, which demonstrates the potential use for ultrahigh resolution displays in an area efficient manner. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The molecular origins of specificity in the assembly of a multienzyme complex.

PubMed

Frank, René A W; Pratap, J Venkatesh; Pei, Xue Y; Perham, Richard N; Luisi, Ben F

2005-08-01

The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative metabolism. We present the first crystal structure of a complex between pyruvate decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of the PDH assembly. The PSBD achieves this dual recognition largely through the addition of a network of interfacial water molecules unique to the E1-PSBD complex. These structural comparisons illuminate our observations that the formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas that of the E3-PSBD complex (from which water is excluded) is entropy driven. Interfacial water molecules thus diversify surface complementarity and contribute to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight into the organization and active site coupling within the approximately 9 MDa PDH complex.

Effects of oxidative modification on thermal aggregation and gel properties of soy protein by malondialdehyde.

PubMed

Wu, Wei; Hua, Yufei; Lin, Qinlu

2014-03-01

Malondialdehyde (MDA) was selected as a representative of lipid peroxidation products to investigate the effects of oxidative modification on thermal aggregation and gel properties of soy protein by lipid peroxidation products. Incubation of soy protein with increasing concentration of MDA resulted in gradual decrease of particle size and content of thermal aggregates during heat denaturation. Oxidative modification by MDA resulted in a decrease in water holding capacity, gel hardness, and gel strength of soy protein gel. An increase in coarseness and interstice of MDA modified protein gel network was accompanied by uneven distribution of interstice as MDA concentration increased. The results showed that degree of thermal aggregation of MDA-modified soy protein gradually decreased as MDA concentration increased, which contributed to a decrease in water holding capacity, gel hardness, and gel strength of MDA-modified soy protein gel.

Modeling the two-locus architecture of divergent pollinator adaptation: how variation in SAD paralogs affects fitness and evolutionary divergence in sexually deceptive orchids.

PubMed

Xu, Shuqing; Schlüter, Philipp M

2015-01-01

Divergent selection by pollinators can bring about strong reproductive isolation via changes at few genes of large effect. This has recently been demonstrated in sexually deceptive orchids, where studies (1) quantified the strength of reproductive isolation in the field; (2) identified genes that appear to be causal for reproductive isolation; and (3) demonstrated selection by analysis of natural variation in gene sequence and expression. In a group of closely related Ophrys orchids, specific floral scent components, namely n-alkenes, are the key floral traits that control specific pollinator attraction by chemical mimicry of insect sex pheromones. The genetic basis of species-specific differences in alkene production mainly lies in two biosynthetic genes encoding stearoyl-acyl carrier protein desaturases (SAD) that are associated with floral scent variation and reproductive isolation between closely related species, and evolve under pollinator-mediated selection. However, the implications of this genetic architecture of key floral traits on the evolutionary processes of pollinator adaptation and speciation in this plant group remain unclear. Here, we expand on these recent findings to model scenarios of adaptive evolutionary change at SAD2 and SAD5, their effects on plant fitness (i.e., offspring number), and the dynamics of speciation. Our model suggests that the two-locus architecture of reproductive isolation allows for rapid sympatric speciation by pollinator shift; however, the likelihood of such pollinator-mediated speciation is asymmetric between the two orchid species O. sphegodes and O. exaltata due to different fitness effects of their predominant SAD2 and SAD5 alleles. Our study not only provides insight into pollinator adaptation and speciation mechanisms of sexually deceptive orchids but also demonstrates the power of applying a modeling approach to the study of pollinator-driven ecological speciation.

[Impact of siRNA-mediated down-regulation of CD147 on human breast cancer cells].

PubMed

Li, Zhenqian; Li, Daoming; Li, Jiangwei; Huang, Pei; Qin, Hui

2015-10-01

To investigate the influence of siRNA-mediated down-regulation of CD147 on growth, proliferation and movement of human breast cancer cell line MDA-MB-231. The protein expression of CD147, MMP-2 and TIMP-2 of the MDA-MB-231 cells were analyzed by ABC. Lentiviral expression vector of CD147 gene was constructed and transfected into MDA-MB-231 cells. RT-PCR and Western blot were used to detect the mRNA and protein level changes of CD147 genes to identify the optimal time point, followed by detection of changes of mRNA and protein expression of MMP-2 and TIMP-2 genes. CCK-8 reagent method and cell scratch test were used to detect the proliferation and migration change of MDA-MB-231 cells. The nude mouse model of breast cancer by hypodermic injection with MDA-MB-231 cells was established to document the effect of CD147 siRNA on the tumor transplants. After transfection of lentiviral expression vector of CD147 gene, protein of CD147, MMP-2 and TIMP-2 were weakly or negative expressed, significantly weaker than those of control group (P < 0.01). After 72 hours of transfection, average down-regulation rate of CD147 and MMP-2 were 96.03% ± 0.84% and 96.03% ± 0.84%, respectively. Both CD147 mRNA and MMP-2 mRNA expression were down-regulated (P < 0.05), while TIMP-2 mRNA expression showed no significant deference (P > 0.05). No less than 2 days after transfection, cell growth of MDA-MB-231 cell line was found significantly inhibited (P < 0.05). After 24 hours of transection, average migration distance of MDA-MB-231 cell line and control group were (0.64 ± 0.12) mm and (4.69 ± 0.85) mm, respectively, which indicated a lower migrate speed. Down regulation of CD147 led to reduction of volume and mass of nude mouses. The growth of the carcinoma transplant was inhibited upon siRNA-mediated down-regulation of CD147 (P < 0.05), with an average tumor mass of (1.85 ± 0.98) g and both reduction of tumor size and tumor mass. CD147 may alter the MMP-2/TIMP-2 balance in MDA-MB-231 cells. CD147 gene silencing inhibits the proliferation and migration of MDA-MB-231 cells and the growth of carcinoma transplants in nude mice.

Impact of Future Emissions and Climate Change on Surface Ozone over China

NASA Astrophysics Data System (ADS)

Ma, C. T.; Westervelt, D. M.; Fiore, A. M.; Rieder, H. E.; Kinney, P.; Wang, S.; Correa, G. J. P.

2017-12-01

China's immense ambient air pollution problem and world-leading greenhouse gas emissions place it at the forefront of global efforts to address these related environmental concerns. Here, we analyze the impact of ECLIPSE (Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants) future emissions scenarios representative of current legislation (CLE) and maximum technically feasible emissions reductions (MFR) on surface ozone (O3) concentrations over China in the 2030s and 2050s, in the context of a changing climate. We use a suite of simulations performed with the NOAA Geophysical Fluid Dynamics Laboratory's AM3 global chemistry-climate model. To estimate the impact of climate change in isolation on Chinese air quality, we hold emissions of air pollutants including O3 precursors fixed at 2015 levels but allow climate (global sea surface temperatures and sea ice cover) to change according to decadal averages for the years 2026-2035 and 2046-2055 from a three-member ensemble of GFDL-CM3 simulations under the RCP8.5 high warming scenario. Evaluation of the present-day simulation (2015 CLE) with observations from 1497 chiefly urban air quality monitoring stations shows that simulated surface O3 is positively biased by 26 ppb on average over the domain of China. Previous studies, however, have shown that the modeled ozone response to changes in NOx emissions over the Eastern United States mirrors the magnitude and structure of observed changes in maximum daily average 8-hour (MDA8) O3 distributions. Therefore, we use the model's simulated changes for the 2030s and 2050s to project changes in policy-relevant MDA8 O3 concentrations. We find an overall increase in MDA8 O3 for CLE scenarios in which emissions of NOx precursors are projected to increase, and under MFR scenarios, an overall decrease, with the highest changes occurring in summertime for both 2030 and 2050 MFR. Under climate change alone, the model simulates a mean summertime decrease of 1.3 ppb and wintertime increase of 3.3 ppb by 2050. Adjustment of the observed site-level MDA8 O3 distribution to reflect regionally interpolated projected changes from AM3 allows us to examine changes in the number of days in exceedance of MDA8 O3 Level I (50 ppb) and Level II (80 ppb) Chinese national ambient air quality standards.

Modeling and Simulation Reliable Spacecraft On-Board Computing

NASA Technical Reports Server (NTRS)

Park, Nohpill

1999-01-01

The proposed project will investigate modeling and simulation-driven testing and fault tolerance schemes for Spacecraft On-Board Computing, thereby achieving reliable spacecraft telecommunication. A spacecraft communication system has inherent capabilities of providing multipoint and broadcast transmission, connectivity between any two distant nodes within a wide-area coverage, quick network configuration /reconfiguration, rapid allocation of space segment capacity, and distance-insensitive cost. To realize the capabilities above mentioned, both the size and cost of the ground-station terminals have to be reduced by using reliable, high-throughput, fast and cost-effective on-board computing system which has been known to be a critical contributor to the overall performance of space mission deployment. Controlled vulnerability of mission data (measured in sensitivity), improved performance (measured in throughput and delay) and fault tolerance (measured in reliability) are some of the most important features of these systems. The system should be thoroughly tested and diagnosed before employing a fault tolerance into the system. Testing and fault tolerance strategies should be driven by accurate performance models (i.e. throughput, delay, reliability and sensitivity) to find an optimal solution in terms of reliability and cost. The modeling and simulation tools will be integrated with a system architecture module, a testing module and a module for fault tolerance all of which interacting through a centered graphical user interface.

A Satellite Data-Driven, Client-Server Decision Support Application for Agricultural Water Resources Management

NASA Technical Reports Server (NTRS)

Johnson, Lee F.; Maneta, Marco P.; Kimball, John S.

2016-01-01

Water cycle extremes such as droughts and floods present a challenge for water managers and for policy makers responsible for the administration of water supplies in agricultural regions. In addition to the inherent uncertainties associated with forecasting extreme weather events, water planners need to anticipate water demands and water user behavior in a typical circumstances. This requires the use decision support systems capable of simulating agricultural water demand with the latest available data. Unfortunately, managers from local and regional agencies often use different datasets of variable quality, which complicates coordinated action. In previous work we have demonstrated novel methodologies to use satellite-based observational technologies, in conjunction with hydro-economic models and state of the art data assimilation methods, to enable robust regional assessment and prediction of drought impacts on agricultural production, water resources, and land allocation. These methods create an opportunity for new, cost-effective analysis tools to support policy and decision-making over large spatial extents. The methods can be driven with information from existing satellite-derived operational products, such as the Satellite Irrigation Management Support system (SIMS) operational over California, the Cropland Data Layer (CDL), and using a modified light-use efficiency algorithm to retrieve crop yield from the synergistic use of MODIS and Landsat imagery. Here we present an integration of this modeling framework in a client-server architecture based on the Hydra platform. Assimilation and processing of resource intensive remote sensing data, as well as hydrologic and other ancillary information occur on the server side. This information is processed and summarized as attributes in water demand nodes that are part of a vector description of the water distribution network. With this architecture, our decision support system becomes a light weight 'app' that connects to the server to retrieve the latest information regarding water demands, land use, yields and hydrologic information required to run different management scenarios. Furthermore, this architecture ensures all agencies and teams involved in water management use the same, up-to-date information in their simulations.

A satellite data-driven, client-server decision support application for agricultural water resources management

NASA Astrophysics Data System (ADS)

Maneta, M. P.; Johnson, L.; Kimball, J. S.

2016-12-01

Water cycle extremes such as droughts and floods present a challenge for water managers and for policy makers responsible for the administration of water supplies in agricultural regions. In addition to the inherent uncertainties associated with forecasting extreme weather events, water planners need to anticipate water demands and water user behavior in atypical circumstances. This requires the use decision support systems capable of simulating agricultural water demand with the latest available data. Unfortunately, managers from local and regional agencies often use different datasets of variable quality, which complicates coordinated action. In previous work we have demonstrated novel methodologies to use satellite-based observational technologies, in conjunction with hydro-economic models and state of the art data assimilation methods, to enable robust regional assessment and prediction of drought impacts on agricultural production, water resources, and land allocation. These methods create an opportunity for new, cost-effective analysis tools to support policy and decision-making over large spatial extents. The methods can be driven with information from existing satellite-derived operational products, such as the Satellite Irrigation Management Support system (SIMS) operational over California, the Cropland Data Layer (CDL), and using a modified light-use efficiency algorithm to retrieve crop yield from the synergistic use of MODIS and Landsat imagery. Here we present an integration of this modeling framework in a client-server architecture based on the Hydra platform. Assimilation and processing of resource intensive remote sensing data, as well as hydrologic and other ancillary information occur on the server side. This information is processed and summarized as attributes in water demand nodes that are part of a vector description of the water distribution network. With this architecture, our decision support system becomes a light weight `app` that connects to the server to retrieve the latest information regarding water demands, land use, yields and hydrologic information required to run different management scenarios. Furthermore, this architecture ensures all agencies and teams involved in water management use the same, up-to-date information in their simulations.

Antiviral function of grouper MDA5 against iridovirus and nodavirus.

PubMed

Huang, Youhua; Yu, Yepin; Yang, Ying; Yang, Min; Zhou, Linli; Huang, Xiaohong; Qin, Qiwei

2016-07-01

Melanoma differentiation-associated gene 5 (MDA5) is a critical member of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family which can recognize viral RNA and enhances antiviral response in host cells. In this study, a MDA5 homolog from orange spotted grouper (Epinephelus coioides) (EcMDA5) was cloned, and its roles on grouper virus infection were characterized. The full-length EcMDA5 cDNA encoded a polypeptide of 982 amino acids with 74% identity with MDA5 homolog from rock bream (Oplegnathus fasciatus). Amino acid alignment analysis indicated that EcMDA5 contained three functional domains: two caspase activation and recruitment domain (CARDs), a DEAD box helicase-like (DExDc) domain, a helicase superfamily C-terminal domain (HELICc), and a C-terminal regulatory domain (RD). Upon challenge with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C), the transcript of EcMDA5 was significantly up-regulated especially at the early stage post-injection. Under fluorescence microscopy, we observed that EcMDA5 mostly localized in the cytoplasm of grouper spleen (GS) cells. Interestingly, during virus infection, the distribution pattern of EcMDA5 was significantly altered in SGIV infected cells, but not in red spotted grouper nervous necrosis virus (RGNNV) infected cells, suggested that EcMDA5 might interact with viral proteins during SGIV infection. The ectopic expression of EcMDA5 in vitro obviously delayed virus infection induced cytopathic effect (CPE) progression and significantly inhibited viral gene transcription of RGNNV and SGIV. Moreover, overexpression of EcMDA5 not only significantly increased interferon (IFN) and IFN-stimulated response element (ISRE) promoter activities in a dose dependent manner, but also enhanced the expression of IRF3, IRF7 and TRAF6. In addition, the transcription level of the proinflammatory factors, including TNF-α, IL-6 and IL-8 were differently altered by EcMDA5 overexpression during SGIV or RGNNV infection, suggesting that the regulation on proinflammatory cytokines by EcMDA5 were also important for RGNNV infection. Together, our results demonstrated for the first time that the inhibitory effect of fish MDA5 on iridovirus replication might be mainly through the regulation of proinflammatory cytokines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Behavior generation strategy of artificial behavioral system by self-learning paradigm for autonomous robot tasks

NASA Astrophysics Data System (ADS)

Dağlarli, Evren; Temeltaş, Hakan

2008-04-01

In this study, behavior generation and self-learning paradigms are investigated for the real-time applications of multi-goal mobile robot tasks. The method is capable to generate new behaviors and it combines them in order to achieve multi goal tasks. The proposed method is composed from three layers: Behavior Generating Module, Coordination Level and Emotion -Motivation Level. Last two levels use Hidden Markov models to manage dynamical structure of behaviors. The kinematics and dynamic model of the mobile robot with non-holonomic constraints are considered in the behavior based control architecture. The proposed method is tested on a four-wheel driven and four-wheel steered mobile robot with constraints in simulation environment and results are obtained successfully.

Molecular graph convolutions: moving beyond fingerprints

PubMed Central

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-01-01

Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID:27558503

The CMIP5 archive architecture: A system for petabyte-scale distributed archival of climate model data

NASA Astrophysics Data System (ADS)

Pascoe, Stephen; Cinquini, Luca; Lawrence, Bryan

2010-05-01

The Phase 5 Coupled Model Intercomparison Project (CMIP5) will produce a petabyte scale archive of climate data relevant to future international assessments of climate science (e.g., the IPCC's 5th Assessment Report scheduled for publication in 2013). The infrastructure for the CMIP5 archive must meet many challenges to support this ambitious international project. We describe here the distributed software architecture being deployed worldwide to meet these challenges. The CMIP5 architecture extends the Earth System Grid (ESG) distributed architecture of Datanodes, providing data access and visualisation services, and Gateways providing the user interface including registration, search and browse services. Additional features developed for CMIP5 include a publication workflow incorporating quality control and metadata submission, data replication, version control, update notification and production of citable metadata records. Implementation of these features have been driven by the requirements of reliable global access to over 1Pb of data and consistent citability of data and metadata. Central to the implementation is the concept of Atomic Datasets that are identifiable through a Data Reference Syntax (DRS). Atomic Datasets are immutable to allow them to be replicated and tracked whilst maintaining data consistency. However, since occasional errors in data production and processing is inevitable, new versions can be published and users notified of these updates. As deprecated datasets may be the target of existing citations they can remain visible in the system. Replication of Atomic Datasets is designed to improve regional access and provide fault tolerance. Several datanodes in the system are designated replicating nodes and hold replicas of a portion of the archive expected to be of broad interest to the community. Gateways provide a system-wide interface to users where they can track the version history and location of replicas to select the most appropriate location for download. In addition to meeting the immediate needs of CMIP5 this architecture provides a basis for the Earth System Modeling e-infrastructure being further developed within the EU FP7 IS-ENES project.

Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection

PubMed Central

Wang, Yaming; Swiecki, Melissa; Cella, Marina; Alber, Gottfried; Schreiber, Robert D; Gilfillan, Susan; Colonna, Marco

2013-01-01

Summary Type I Interferons (IFN-I) promote antiviral CD8+T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill-defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I are induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8+T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8+T cell responses. In the absence of MDA5, CD8+T cell responses to acute infection rely on CD4+T cell help, and loss of both CD4+T cells and MDA5 results in CD8+T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8+T cells, promoting viral clearance. Thus, effective antiviral CD8+T cell responses depend on the timing and magnitude of IFN-I responses. PMID:22704623

Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection.

PubMed

Wang, Yaming; Swiecki, Melissa; Cella, Marina; Alber, Gottfried; Schreiber, Robert D; Gilfillan, Susan; Colonna, Marco

2012-06-14

Type I interferon (IFN-I) promotes antiviral CD8(+)T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I is induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8(+)T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8(+)T cell responses. In the absence of MDA5, CD8(+)T cell responses to acute infection rely on CD4(+)T cell help, and loss of both CD4(+)T cells and MDA5 results in CD8(+)T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8(+)T cells, promoting viral clearance. Thus, effective antiviral CD8(+)T cell responses depend on the timing and magnitude of IFN-I production. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of vinpocetine on random skin flap survival in rats.

PubMed

Xiao-Xiao, Tao; Sen-Min, Wu; Ding-Sheng, Lin

2013-07-01

The effect of vinpocetine on flap survival, vascular endothelial growth factor (VEGF) expression, and superoxide dismutase (SOD) and malondialdehyde (MDA) contents were evaluated in this study. The McFarlane flap model was established in 20 rats and evaluated within two groups. Postoperative celiac injection was given for 7 days in the two groups: vinpocetine was applied in Group 1, and the same volume of saline was applied in Group 2. Flap necrosis was measured on day 7 by cellophane in all groups. VEGF expression was determined using immunohistochemical methods on tissue samples taken after 7 days of injections. SOD and MDA contents were examined according to the Kit (reagent instructions). Vinpocetine significantly reduced necrosis area in Group 1 (p < 0.05). VEGF expression and SOD contents were significantly increased in Group 1 compared with Group 2 (p < 0.01), whereas MDA level was reduced (p < 0.05). This experimental study demonstrates that vinpocetine improves survival of random skin flaps, promotes neovascularization, and increases VEGF expression. Meanwhile, vinpocetine has a protective effect against ischemia-reperfusion injury by improving SOD vitality and decreasing MDA value. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Oxidative stress responses in gills of tilapia (Oreochromis niloticus) at different salinities

NASA Astrophysics Data System (ADS)

Handayani, Kiki Syaputri; Novianty, Zahra; Saputri, Miftahul Rohmah; Irawan, Bambang; Soegianto, Agoes

2017-08-01

The objective of present study is to evaluate the impact of different salinities on the levels of CAT, GSH and MDA of the gills of Nile tilapia (Oreochromis niloticus). Nile tilapia was treated by exposure to salinities concentration 0 ‰, 5 ‰ and 10 ‰. Research models were weakened and sacrificed, then took the left and right sides of the gills. The result of gills homogenity was centrifuged for supernatan, then supernatan was proceed with testing levels of CAT, GSH and MDA by ELISA assay methods. The levels of CAT in gills were significantly higher at 10 ‰ than at 5 ‰ and 0 ‰. The levels of GSH in gills were significantly higher at 0 ‰ than 5 ‰. The levels of GSH in gills at 5 ‰ and 10 ‰ salinities were not significantly different. The levels of MDA in gills at salinity 10 ‰ and 5 ‰ were higher than in control gills at 0 ‰ salinities. This occurs because the salinity of 10 ‰ salinity was optimal for live of fish tilapia. In conclusion, salinity impact the increasing of CAT, GSH, and MDA levels in gills of Nile tilapia.

Duration of ultrasound-mediated enhanced plasma membrane permeability.

PubMed

Lammertink, Bart; Deckers, Roel; Storm, Gert; Moonen, Chrit; Bos, Clemens

2015-03-30

Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2 h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3 h after sonication. Copyright © 2014 Elsevier B.V. All rights reserved.

The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths

PubMed Central

Anderson, Roy; Truscott, James; Hollingsworth, T. Deirdre

2014-01-01

A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration (MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R0), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission. PMID:24821921

The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths.

PubMed

Anderson, Roy; Truscott, James; Hollingsworth, T Deirdre

2014-01-01

A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration (MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R0), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission.

Preneoplastic lesion growth driven by the death of adjacent normal stem cells

PubMed Central

Chao, Dennis L.; Eck, J. Thomas; Brash, Douglas E.; Maley, Carlo C.; Luebeck, E. Georg

2008-01-01

Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication. PMID:18815380

Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer

PubMed Central

Adkins, Chris E.; Mohammad, Afroz S.; Terrell-Hall, Tori; Dolan, Emma L.; Shah, Neal; Sechrest, Emily; Griffith, Jessica; Lockman, Paul R.

2016-01-01

The blood brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing). Permeability was assessed using quantitative autoradiography and fluorescence microscopy by co-administration of the tracers 14C-aminoisobutyric acid (AIB) and Texas Red conjugated dextran (TRD) prior to euthanasia. Each experimental brain metastases model produced variably increased permeability to both tracers; additionally, the magnitude of heterogeneity was different among each model with the highest ranges observed in the SUM190 (up to 45-fold increase in AIB) and MDA-MB-231BR-HER2 (up to 33-fold in AIB) models while the lowest range was observed in the JIMT-1-BR3 (up to 5.5-fold in AIB) model. There was no strong correlation observed between lesion size and permeability in any of these preclinical models of brain metastases. Interestingly, the experimental models resulting in smaller mean metastases size resulted in shorter median survival while models producing larger lesions had longer median survival. These findings strengthen the evidence of heterogeneity in brain metastases of breast cancer by utilizing five unique experimental models and simultaneously emphasize the challenges of chemotherapeutic approaches to treat brain metastases. PMID:26944053

Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia.

PubMed

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J; Fischer, Peter U; Kollie, Karsor; Bolay, Fatorma K

2016-03-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. © The American Society of Tropical Medicine and Hygiene.

Vitamin C protects rat cerebellum and encephalon from oxidative stress following exposure to radiofrequency wave generated by a BTS antenna model.

PubMed

Akbari, Abolfazl; Jelodar, Gholamali; Nazifi, Saeed

2014-06-01

Radio frequency wave (RFW) generated by base transceiver station has been reported to produce deleterious effects on the central nervous system function, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW-induced oxidative stress in the cerebellum and encephalon and the prophylactic effect of vitamin C on theses tissues by measuring the antioxidant enzymes activity, including: glutathione peroxidase, superoxide dismutase, catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four equal groups. The control group; the control-vitamin C group received L-ascorbic acid (200 mg/kg of body weight/day by gavage) for 45 days. The RFW group was exposed to RFW and the RFW+ vitamin C group was exposed to RFW and received vitamin C. At the end of the experiment, all groups were killed and encephalon and cerebellum of all rats were removed and stored at -70 °C for measurement of antioxidant enzymes activity and MDA. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p < 0.05). The protective role of vitamin C in the treated group improved antioxidant enzymes activity and reduced MDA compared with the test group (p < 0.05). It can be concluded that RFW causes oxidative stress in the brain and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse.

PubMed

O'Callaghan, J P; Miller, D B

1994-08-01

Dopaminergic (DA) and serotonergic (5-HT) projections to striatum and cortex have been implicated as the primary targets of substituted amphetamine (AMP)-induced neurotoxicity, largely on the basis of the propensity of these compounds to cause protracted decrements in DA and 5-HT rather than on the basis of AMP-induced alterations of indices linked to neural damage. Moreover, most studies of AMP-induced neurotoxicity, regardless of the endpoints assessed, have been conducted using a rat model; relatively little attention has been focused on the effects of these compounds in the mouse. Here, we evaluated the potential neurotoxic effects of d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA), d-methylene-dioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in the C57BL6/J mouse. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was taken as the main index of AMP-induced neural damage. A silver degeneration stain also was used to obtain direct evidence of AMP-induced neuronal damage. Assays of tyrosine hydroxylase (TH), DA and 5-HT were used to assess effects on DA and 5-HT systems. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg), d-MDMA (20 mg/kg) or d-FEN (25 mg/kg) every 2 hr for a total of four s.c. injections. d-METH, d-MDA and d-MDMA caused a large (300%) increase in striatal GFAP that resolved by 3 weeks and a 50 to 75% decrease in TH and DA that did not resolve. d-METH, d-MDA and d-MDMA also caused fiber and terminal degeneration in striatum as revealed by silver staining. d-FEN did not affect any parameters in striatum. d-METH, d-MDA and d-MDMA also increased GFAP in cortex, effects that were associated with small (10-25%) and transient decrements in cortical 5-HT. d-FEN caused prolonged (weeks) decrements (20%) in cortical 5-HT but did not affect cortical GFAP. The effects of d-METH, d-MDA and d-MDMA were stereoselective and were blocked by pretreatment with MK-801. Core temperature was slightly elevated by d-METH, d-MDA and d-MDMA but was dramatically lowered by d-FEN. The data suggest that d-METH, d-MDA and d-MDMA, but not d-FEN, produce damage to neural elements of mouse striatum and cortex.

Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks.

PubMed

Chami, Goylette F; Kontoleon, Andreas A; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B; Tukahebwa, Edridah M; Dunne, David W

2017-06-01

Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermectin were administered for one month in community-directed MDA to treat Schistosoma mansoni, hookworm, and lymphatic filariasis. Self-reported treatment outcomes, socioeconomic characteristics, friendship networks, and health advice networks were collected. We investigated systematically missed coverage and noncompliance. Coverage was defined as an eligible person being offered at least one drug by CMDs; compliance included ingesting at least one of the offered drugs. These outcomes were analyzed as a two-stage process using a Heckman selection model. To further assess if MDA through CMDs was working as intended, we examined the probability of accurate drug administration of 1) praziquantel, 2) both albendazole and ivermectin, and 3) all drugs. This analysis was conducted using bivariate Probit regression. Four indicators from each social network were examined: degree, betweenness centrality, closeness centrality, and the presence of a direct connection to CMDs. All models accounted for nested household and village standard errors. CMDs were more likely to offer medicines, and to accurately administer the drugs as trained by the national control programme, to individuals with high friendship degree (many connections) and high friendship closeness centrality (households that were only a short number of steps away from all other households in the network). Though high (88.59%), additional compliance was associated with directly trusting CMDs for health advice. Effective treatment provision requires addressing CMD biases towards influential, well-embedded individuals in friendship networks and utilizing health advice networks to increase village trust in CMDs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human embryonic stem cell-derived endothelial cells as cellular delivery vehicles for treatment of metastatic breast cancer.

PubMed

Su, Weijun; Wang, Lina; Zhou, Manqian; Liu, Ze; Hu, Shijun; Tong, Lingling; Liu, Yanhua; Fan, Yan; Kong, Deling; Zheng, Yizhou; Han, Zhongchao; Wu, Joseph C; Xiang, Rong; Li, Zongjin

2013-01-01

Endothelial progenitor cells (EPCs) have shown tropism towards primary tumors or metastases and are thus potential vehicles for targeting tumor therapy. However, the source of adult EPCs is limited, which highlights the need for a consistent and renewable source of endothelial cells for clinical applications. Here, we investigated the potential of human embryonic stem cell-derived endothelial cells (hESC-ECs) as cellular delivery vehicles for therapy of metastatic breast cancer. In order to provide an initial assessment of the therapeutic potency of hESC-ECs, we treated human breast cancer MDA-MB-231 cells with hESC-EC conditioned medium (EC-CM) in vitro. The results showed that hESC-ECs could suppress the Wnt/β-catenin signaling pathway and thereby inhibit the proliferation and migration of MDA-MB-231 cells. To track and evaluate the possibility of hESC-EC-employed therapy, we employed the bioluminescence imaging (BLI) technology. To study the therapeutic potential of hESC-ECs, we established lung metastasis models by intravenous injection of MDA-MB-231 cells labeled with firefly luciferase (Fluc) and green fluorescent protein (GFP) to NOD/SCID mice. In mice with lung metastases, we injected hESC-ECs armed with herpes simplex virus truncated thymidine kinase (HSV-ttk) intravenously on days 11, 16, 21, and 26 after MDA-MB-231 cell injection. The NOD/SCID mice were subsequently treated with ganciclovir (GCV), and the growth status of tumor was monitored by Fluc imaging. We found that MDA-MB-231 tumors were significantly inhibited by intravenously injected hESC-ECs. The tumor-suppressive effects of the hESC-ECs, by inhibiting Wnt/β-catenin signaling pathway and inducing tumor cell death through bystander effect in human metastatic breast cancer model, provide previously unexplored therapeutic modalities for cancer treatment.

International Space Station Electric Power System Performance Code-SPACE

NASA Technical Reports Server (NTRS)

Hojnicki, Jeffrey; McKissock, David; Fincannon, James; Green, Robert; Kerslake, Thomas; Delleur, Ann; Follo, Jeffrey; Trudell, Jeffrey; Hoffman, David J.; Jannette, Anthony;

System Architecture Development for Energy and Water Infrastructure Data Management and Geovisual Analytics

NASA Astrophysics Data System (ADS)

Berres, A.; Karthik, R.; Nugent, P.; Sorokine, A.; Myers, A.; Pang, H.

2017-12-01

Building an integrated data infrastructure that can meet the needs of a sustainable energy-water resource management requires a robust data management and geovisual analytics platform, capable of cross-domain scientific discovery and knowledge generation. Such a platform can facilitate the investigation of diverse complex research and policy questions for emerging priorities in Energy-Water Nexus (EWN) science areas. Using advanced data analytics, machine learning techniques, multi-dimensional statistical tools, and interactive geovisualization components, such a multi-layered federated platform is being developed, the Energy-Water Nexus Knowledge Discovery Framework (EWN-KDF). This platform utilizes several enterprise-grade software design concepts and standards such as extensible service-oriented architecture, open standard protocols, event-driven programming model, enterprise service bus, and adaptive user interfaces to provide a strategic value to the integrative computational and data infrastructure. EWN-KDF is built on the Compute and Data Environment for Science (CADES) environment in Oak Ridge National Laboratory (ORNL).

Persistent 'hotspots' of lymphatic filariasis microfilaraemia despite 14 years of mass drug administration in Ghana.

PubMed

Biritwum, Nana-Kwadwo; Yikpotey, Paul; Marfo, Benjamin K; Odoom, Samuel; Mensah, Ernest O; Asiedu, Odame; Alomatu, Bright; Hervie, Edward T; Yeboah, Abednego; Ade, Serge; Hinderaker, Sven G; Reid, Anthony; Takarinda, Kudakwashe C; Koudou, Benjamin; Koroma, Joseph B

2016-12-01

Among the 216 districts in Ghana, 98 were declared endemic for lymphatic filariasis in 1999 after mapping. Pursuing the goal of elimination, WHO recommends annual treatment using mass drugs administration (MDA) for at least 5 years. MDA was started in the country in 2001 and reached national coverage in 2006. By 2014, 69 districts had 'stopped-MDA' (after passing the transmission assessment survey) while 29 others remained with persistent microfilaraemia (mf) prevalence (≥1%) despite more than 11 years of MDA and were classified as 'hotspots'. An ecological study was carried out to compare baseline mf prevalence and anti-microfilaria interventions between hotspot and stopped-MDA districts. Baseline mf prevalence was significantly higher in hotspots than stopped-MDA districts (p<0.001). After three years of MDA, there was a significant decrease in mf prevalence in hotspot districts, but it was still higher than in stopped-MDA districts. The number of MDA rounds was slightly higher in hotspot districts (p<0.001), but there were no differences in coverage of MDA or long-lasting-insecticide-treated nets. The main difference in hotspots and stopped-MDA districts was a high baseline mf prevalence. This finding indicates that the recommended 5-6 rounds annual treatment may not achieve interruption of transmission. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Lung counting: comparison of detector performance with a four detector array that has either metal or carbon fibre end caps, and the effect on mda calculation.

PubMed

Ahmed, Asm Sabbir; Hauck, Barry; Kramer, Gary H

2012-08-01

This study described the performance of an array of high-purity Germanium detectors, designed with two different end cap materials-steel and carbon fibre. The advantages and disadvantages of using this detector type in the estimation of the minimum detectable activity (MDA) for different energy peaks of isotope (152)Eu were illustrated. A Monte Carlo model was developed to study the detection efficiency for the detector array. A voxelised Lawrence Livermore torso phantom, equipped with lung, chest plates and overlay plates, was used to mimic a typical lung counting protocol with the array of detectors. The lung of the phantom simulated the volumetric source organ. A significantly low MDA was estimated for energy peaks at 40 keV and at a chest wall thickness of 6.64 cm.

Architectural-level power estimation and experimentation

NASA Astrophysics Data System (ADS)

Ye, Wu

With the emergence of a plethora of embedded and portable applications and ever increasing integration levels, power dissipation of integrated circuits has moved to the forefront as a design constraint. Recent years have also seen a significant trend towards designs starting at the architectural (or RT) level. Those demand accurate yet fast RT level power estimation methodologies and tools. This thesis addresses issues and experiments associate with architectural level power estimation. An execution driven, cycle-accurate RT level power simulator, SimplePower, was developed using transition-sensitive energy models. It is based on the architecture of a five-stage pipelined RISC datapath for both 0.35mum and 0.8mum technology and can execute the integer subset of the instruction set of SimpleScalar . SimplePower measures the energy consumed in the datapath, memory and on-chip buses. During the development of SimplePower , a partitioning power modeling technique was proposed to model the energy consumed in complex functional units. The accuracy of this technique was validated with HSPICE simulation results for a register file and a shifter. A novel, selectively gated pipeline register optimization technique was proposed to reduce the datapath energy consumption. It uses the decoded control signals to selectively gate the data fields of the pipeline registers. Simulation results show that this technique can reduce the datapath energy consumption by 18--36% for a set of benchmarks. A low-level back-end compiler optimization, register relabeling, was applied to reduce the on-chip instruction cache data bus switch activities. Its impact was evaluated by SimplePower. Results show that it can reduce the energy consumed in the instruction data buses by 3.55--16.90%. A quantitative evaluation was conducted for the impact of six state-of-art high-level compilation techniques on both datapath and memory energy consumption. The experimental results provide a valuable insight for designers to develop future power-aware compilation frameworks for embedded systems.

Orthographic influences on division of labor in learning to read Chinese and English: Insights from computational modeling

PubMed Central

Yang, Jianfeng; Shu, Hua; McCandliss, Bruce D.; Zevin, Jason D.

2013-01-01

Learning to read any language requires learning to map among print, sound and meaning. Writing systems differ in a number of factors that influence both the ease and rate with which reading skill can be acquired, as well as the eventual division of labor between phonological and semantic processes. Further, developmental reading disability manifests differently across writing systems, and may be related to different deficits in constitutive processes. Here we simulate some aspects of reading acquisition in Chinese and English using the same model architecture for both writing systems. The contribution of semantic and phonological processing to literacy acquisition in the two languages is simulated, including specific effects of phonological and semantic deficits. Further, we demonstrate that similar patterns of performance are observed when the same model is trained on both Chinese and English as an "early bilingual." The results are consistent with the view that reading skill is acquired by the application of statistical learning rules to mappings among print, sound and meaning, and that differences in the typical and disordered acquisition of reading skill between writing systems are driven by differences in the statistical patterns of the writing systems themselves, rather than differences in cognitive architecture of the learner. PMID:24587693

Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat model.

PubMed

Zhang, Weili; Li, Yuhui; Ge, Zhiming

2017-09-01

Given study evaluates the cardioprotective effect of crocetin in myocardial infracted (MI) rats. MI was produced by administering isoproterenol (90mg/kg/day, i.p.) in rats for two consecutive days. all the animals were divided in to four groups such as control group receives only saline; MI group which receives only isoproterenol and crocetin treated group which receives crocetin (50, 100 and 200mg/kg/day, p.o.) for the duration of 15 days. At the end of dosing left ventricular functions was assessed to estimate its effect on cardiac functions. Catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), creatine kinase (CK-MB), lactate dehydrogenase (LDH) and inflammatory cytokines were determined in the cardiac tissue homogenate. Histopathology study was also carried out using hematoxylin and eosin staining. Immunohistochemistry was done for the estimation of Caspase-3, Bcl-2, Bax and Nrf-2 level in the myocardial tissues of MI rats. Result of the study suggested that GSH, CAT, CK-MB, and LDH were (p<0.01) increased in the tissue homogenate of crocetin treated group than MI group. However crocetin significantly (p<0.01) decreases the level of MDA and activity of SOD in the tissue homogenate than MI group. It was observed that treatment with crocetin attenuates the level of inflammatory cytokines in the myocardial tissues of MI rats. Moreover level of caspase-3, Bax and Nrf-2 significantly reduced and Bcl-2 enhanced in the myocardial tissues of MI rats than MI group. The altered cellular architecture of heart tissue sections in the myocardial infracted rats were reversed by administration of crocetin treatment. Taking all these data together, it may be suggested that the crocetin act as a possible protective agent in myocardial infarction by decreasing oxidative stress and inflammatory cytokines and thereby attenuates the apoptosis of myocardial cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

PubMed

Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

2014-08-01

Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of malondialdehyde modification on the in vitro digestibility of soy protein isolate.

PubMed

Chen, Nannan; Zhao, Qiangzhong; Sun, Weizheng; Zhao, Mouming

2013-12-11

Soy protein isolate (SPI) was modified by lipid peroxidation product malondialdehyde (MDA), and the in vitro digestibility of modified SPI was investigated. Results indicated that incubation with increasing MDA concentration resulted in significant carbonyl group generation and loss of free amino groups of SPI. Fluorescence loss of natural tryptophan and formation of Schiff base were observed. Noncovalent interaction between molecules was enhanced and became the main force that led to the solubility reduction of MDA-modified SPI. Differential scanning calorimetry (DSC) indicated that SPI had higher thermal stability and lower total calorimetric enthalpy after MDA pretreatment. Electrophoresis showed that β-conglycinin was more sensitive to MDA modification. In vitro digestion indicated that MDA could induce non-disulfide covalent polymer of SPI, which could not be digested by pepsin and pancreatin. β subunits of β-conglycinin became more resistant to digestion with increasing MDA concentration. Evaluation of the free amino acid profile in the digests indicated that MDA-modified SPI had deteriorating nutritive quality.

Domain specific software architectures: Command and control

NASA Technical Reports Server (NTRS)

Braun, Christine; Hatch, William; Ruegsegger, Theodore; Balzer, Bob; Feather, Martin; Goldman, Neil; Wile, Dave

1992-01-01

GTE is the Command and Control contractor for the Domain Specific Software Architectures program. The objective of this program is to develop and demonstrate an architecture-driven, component-based capability for the automated generation of command and control (C2) applications. Such a capability will significantly reduce the cost of C2 applications development and will lead to improved system quality and reliability through the use of proven architectures and components. A major focus of GTE's approach is the automated generation of application components in particular subdomains. Our initial work in this area has concentrated in the message handling subdomain; we have defined and prototyped an approach that can automate one of the most software-intensive parts of C2 systems development. This paper provides an overview of the GTE team's DSSA approach and then presents our work on automated support for message processing.

Overview of the Phoenix Entry, Descent and Landing System Architecture

NASA Technical Reports Server (NTRS)

Grover, Myron R., III; Cichy, Benjamin D.; Desai, Prasun N.

2008-01-01

NASA s Phoenix Mars Lander began its journey to Mars from Cape Canaveral, Florida in August 2007, but its journey to the launch pad began many years earlier in 1997 as NASA s Mars Surveyor Program 2001 Lander. In the intervening years, the entry, descent and landing (EDL) system architecture went through a series of changes, resulting in the system flown to the surface of Mars on May 25th, 2008. Some changes, such as entry velocity and landing site elevation, were the result of differences in mission design. Other changes, including the removal of hypersonic guidance, the reformulation of the parachute deployment algorithm, and the addition of the backshell avoidance maneuver, were driven by constant efforts to augment system robustness. An overview of the Phoenix EDL system architecture is presented along with rationales driving these architectural changes.

Maternal diets with low healthy eating index or Mediterranean diet adherence scores are associated with high cord-blood insulin levels and insulin resistance markers at birth.

PubMed

Gesteiro, E; Rodríguez Bernal, B; Bastida, S; Sánchez-Muniz, F J

2012-09-01

Few studies have used healthy eating index (HEI) and mediterranean diet adherence (MDA) scores to evaluate the diet quality during pregnancy. To determine the relationship between first trimester diet quality and insulin sensitivity/resistance biomarkers at birth. Cord-blood insulin sensitivity/resistance biomarkers of the offspring of 35 women whose diets were 'adequate' or 'inadequate' according to their HEI score (>70 or ≤ 70, respectively) and their 13-point MDA score (≥ 7 or <7, respectively). Low HEI-score diets contained less (g/1000 kcal) carbohydrates (CHO; P=0.027) and fibre (P=0.011), and more fats (P<0.001) and cholesterol (P<0.001), and contributed (percentage contribution to total energy (%En)) fewer CHO (P=0.005), more fats (P=<0.001) and saturated fatty acid (SFA; P=0.002) than their high HEI-score counterparts. Low MDA-score diets contained less (g/1000 kcal) fibre (P<0.001) and more cholesterol (P=0.05), had lower polyunsaturated fatty acids+monounsaturated fatty acid/SFA (PUFA+MUFA/SFA; P=0.05) and higher SFA/CHO (P=0.021) and ω-6/ω-3 PUFA ratios (P=0.044) than their respective counterparts. Women consuming the low HEI- or low MDA-score diets had low-fasting glycaemia (P=0.016 or P=0.025, respectively) but delivered infants with high insulinaemia (P=0.048 or P=0.017, respectively), homeostatic model assessment for insulin resistance (HOMA-IR; P=0.031 or P=0.049, respectively) and glycaemia (P=0.018 or P=0.048, respectively). The relative risk (RR) of high-neonatal glycaemia and insulinaemia were 7.6 (P=0.008) and 6.7 (P=0.017) for low vs high HEI-score groups. High HOMA-IR and high glucose RR were, respectively, 3.4 (P=0.043) and 3.9 (P=0.016) in neonates from the <7 MDA- vs ≥ 7 MDA-score group. These RRs were not affected by potential confounders. Maternal diets with low HEI- or MDA-scores during the first trimester of pregnancy negatively affect insulin resistance markers at birth.

Hydrodynamic controls on the long-term construction of large river floodplains and alluvial ridges

NASA Astrophysics Data System (ADS)

Nicholas, Andrew; Aalto, Rolf; Sambrook Smith, Gregory; Schwendel, Arved

2017-04-01

Floodplain construction involves the interplay between channel belt sedimentation and avulsion, overbank deposition of fines, and sediment reworking by channel migration. Each of these processes is controlled, in part, by within-channel and/or overbank hydraulics. However, while spatially-distributed hydrodynamic models are used routinely to simulate floodplain inundation and overbank sedimentation during individual floods, most existing models of long-term floodplain construction and alluvial architecture do not account for flood hydraulics explicitly. Instead, floodplain sedimentation is typically modelled as an exponential function of distance from the river, and avulsion thresholds are defined using topographic indices that quantify alluvial ridge morphology (e.g., lateral:downstream slope ratios or metrics of channel belt super-elevation). Herein, we apply a hydraulically driven model of floodplain evolution, in order to quantify the controls on alluvial ridge construction and avulsion likelihood in large lowland rivers. We combine a simple model of meander migration and cutoff with a 2D grid-based model of flood hydrodynamics and overbank sedimentation. The latter involves a finite volume solution of the shallow water equations and an advection-diffusion model for suspended sediment transport. The model is used to carry out a series of numerical experiments to investigate floodplain construction for a range of flood regimes and sediment supply scenarios, and results are compared to field data from the Rio Beni system, northern Bolivia. Model results, supported by field data, illustrate that floodplain sedimentation is characterised by a high degree of intermittency that is driven by autogenic mechanisms (i.e. even in the absence of temporal variations in flood magnitude and sediment supply). Intermittency in overbank deposits occurs over a range of temporal and spatial scales, and is associated with the interaction between channel migration dynamics and crevasse splay formation. Moreover, alluvial ridge construction, by splay deposition, is controlled by the balance between in-channel and overbank sedimentation rates, and by ridge reworking linked to channel migration. The resulting relationship between sedimentation rates, ridge morphology and avulsion likelihood is more complex than that which is incorporated with existing models of long-term floodplain construction that neglect flood hydraulics. These results have implications for the interpretation of floodplain deposits as records of past flood regimes, and for the controls on the alluvial architecture of large river floodplains.

Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

PubMed

Hussain, Tajamul; Al-Attas, Omar S; Alrokayan, Salman A; Ahmed, Mukhtar; Al-Daghri, Nasser M; Al-Ameri, Salman; Pervez, Shamsh; Dewangan, Shippi; Mohammed, Arif; Gambhir, Dikshit; Sumague, Terrance S

2016-07-01

Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma.

PubMed

Oyesanya, Regina A; Bhatia, Shilpa; Menezes, Mitchell E; Dumur, Catherine I; Singh, Karan P; Bae, Sejong; Troyer, Dean A; Wells, Robert B; Sauter, Edward R; Sidransky, David; Fisher, Paul B; Semmes, Oliver J; Dasgupta, Santanu

2014-01-01

Little is known about the molecular pathways regulating poor differentiation and invasion of head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to determine the role of MDA-9/Syntenin, a metastasis associated molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co-localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor. Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed following over-expression of MDA-9/Syntenin in immortalized oral epithelial cells. Our results suggest that early induction of MDA-9/Syntenin expression influences HNSCC progression and should be further evaluated for potential biomarker development.

MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma

PubMed Central

Dumur, Catherine I.; Singh, Karan P; Bae, Sejong; Troyer, Dean A.; Wells, Robert B.; Sauter, Edward R.; Sidransky, David; Fisher, Paul B.; Semmes, Oliver J.; Dasgupta, Santanu

2014-01-01

Little is known about the molecular pathways regulating poor differentiation and invasion of head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to determine the role of MDA-9/Syntenin, a metastasis associated molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co-localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor. Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed following over-expression of MDA-9/Syntenin in immortalized oral epithelial cells. Our results suggest that early induction of MDA-9/Syntenin expression influences HNSCC progression and should be further evaluated for potential biomarker development. PMID:25593999

Seasonal prediction of US summertime ozone using statistical analysis of large scale climate patterns.

PubMed

Shen, Lu; Mickley, Loretta J

2017-03-07

We develop a statistical model to predict June-July-August (JJA) daily maximum 8-h average (MDA8) ozone concentrations in the eastern United States based on large-scale climate patterns during the previous spring. We find that anomalously high JJA ozone in the East is correlated with these springtime patterns: warm tropical Atlantic and cold northeast Pacific sea surface temperatures (SSTs), as well as positive sea level pressure (SLP) anomalies over Hawaii and negative SLP anomalies over the Atlantic and North America. We then develop a linear regression model to predict JJA MDA8 ozone from 1980 to 2013, using the identified SST and SLP patterns from the previous spring. The model explains ∼45% of the variability in JJA MDA8 ozone concentrations and ∼30% variability in the number of JJA ozone episodes (>70 ppbv) when averaged over the eastern United States. This seasonal predictability results from large-scale ocean-atmosphere interactions. Warm tropical Atlantic SSTs can trigger diabatic heating in the atmosphere and influence the extratropical climate through stationary wave propagation, leading to greater subsidence, less precipitation, and higher temperatures in the East, which increases surface ozone concentrations there. Cooler SSTs in the northeast Pacific are also associated with more summertime heatwaves and high ozone in the East. On average, models participating in the Atmospheric Model Intercomparison Project fail to capture the influence of this ocean-atmosphere interaction on temperatures in the eastern United States, implying that such models would have difficulty simulating the interannual variability of surface ozone in this region.

Seasonal prediction of US summertime ozone using statistical analysis of large scale climate patterns

PubMed Central

Mickley, Loretta J.

2017-01-01

We develop a statistical model to predict June–July–August (JJA) daily maximum 8-h average (MDA8) ozone concentrations in the eastern United States based on large-scale climate patterns during the previous spring. We find that anomalously high JJA ozone in the East is correlated with these springtime patterns: warm tropical Atlantic and cold northeast Pacific sea surface temperatures (SSTs), as well as positive sea level pressure (SLP) anomalies over Hawaii and negative SLP anomalies over the Atlantic and North America. We then develop a linear regression model to predict JJA MDA8 ozone from 1980 to 2013, using the identified SST and SLP patterns from the previous spring. The model explains ∼45% of the variability in JJA MDA8 ozone concentrations and ∼30% variability in the number of JJA ozone episodes (>70 ppbv) when averaged over the eastern United States. This seasonal predictability results from large-scale ocean–atmosphere interactions. Warm tropical Atlantic SSTs can trigger diabatic heating in the atmosphere and influence the extratropical climate through stationary wave propagation, leading to greater subsidence, less precipitation, and higher temperatures in the East, which increases surface ozone concentrations there. Cooler SSTs in the northeast Pacific are also associated with more summertime heatwaves and high ozone in the East. On average, models participating in the Atmospheric Model Intercomparison Project fail to capture the influence of this ocean–atmosphere interaction on temperatures in the eastern United States, implying that such models would have difficulty simulating the interannual variability of surface ozone in this region. PMID:28223483

Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells

PubMed Central

Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A.; García-Pérez, Carlos A.; Guerrero-Rodríguez, Sandra L.; Ruiz, Angel J.; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M.; Velasco-Velázquez, Marco A.

2016-01-01

CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24− cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists. PMID:27009862

Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells.

PubMed

Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A; García-Pérez, Carlos A; Guerrero-Rodríguez, Sandra L; Ruiz-Moreno, Angel J; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M; Velasco-Velázquez, Marco A

2016-04-26

CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24- cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists.

Concept of Operations for Collaboration and Discovery from Big Data Across Enterprise Data Warehouses

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

Olama, Mohammed M; Nutaro, James J; Sukumar, Sreenivas R

2013-01-01

The success of data-driven business in government, science, and private industry is driving the need for seamless integration of intra and inter-enterprise data sources to extract knowledge nuggets in the form of correlations, trends, patterns and behaviors previously not discovered due to physical and logical separation of datasets. Today, as volume, velocity, variety and complexity of enterprise data keeps increasing, the next generation analysts are facing several challenges in the knowledge extraction process. Towards addressing these challenges, data-driven organizations that rely on the success of their analysts have to make investment decisions for sustainable data/information systems and knowledge discovery. Optionsmore » that organizations are considering are newer storage/analysis architectures, better analysis machines, redesigned analysis algorithms, collaborative knowledge management tools, and query builders amongst many others. In this paper, we present a concept of operations for enabling knowledge discovery that data-driven organizations can leverage towards making their investment decisions. We base our recommendations on the experience gained from integrating multi-agency enterprise data warehouses at the Oak Ridge National Laboratory to design the foundation of future knowledge nurturing data-system architectures.« less

Archetype Model-Driven Development Framework for EHR Web System

PubMed Central

Kimura, Eizen; Ishihara, Ken

2013-01-01

Objectives This article describes the Web application framework for Electronic Health Records (EHRs) we have developed to reduce construction costs for EHR sytems. Methods The openEHR project has developed clinical model driven architecture for future-proof interoperable EHR systems. This project provides the specifications to standardize clinical domain model implementations, upon which the ISO/CEN 13606 standards are based. The reference implementation has been formally described in Eiffel. Moreover C# and Java implementations have been developed as reference. While scripting languages had been more popular because of their higher efficiency and faster development in recent years, they had not been involved in the openEHR implementations. From 2007, we have used the Ruby language and Ruby on Rails (RoR) as an agile development platform to implement EHR systems, which is in conformity with the openEHR specifications. Results We implemented almost all of the specifications, the Archetype Definition Language parser, and RoR scaffold generator from archetype. Although some problems have emerged, most of them have been resolved. Conclusions We have provided an agile EHR Web framework, which can build up Web systems from archetype models using RoR. The feasibility of the archetype model to provide semantic interoperability of EHRs has been demonstrated and we have verified that that it is suitable for the construction of EHR systems. PMID:24523991

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta

PubMed Central

Pal, Siladitya; Tsamis, Alkiviadis; Pasta, Salvatore; D'Amore, Antonio; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2014-01-01

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovaular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber microarchitecture, obtained in a parallel study from multi-photon microopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence. PMID:24484644

The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study

PubMed Central

Tanrikulu, Yusuf; Şahin, Mefaret; Kismet, Kemal; Kilicoglu, Sibel Serin; Devrim, Erdinc; Tanrikulu, Ceren Sen; Erdemli, Esra; Erel, Serap; Bayraktar, Kenan; Akkus, Mehmet Ali

2013-01-01

Liver ischemia reperfusion injury (IRI) is an important pathologic process leading to bodily systemic effects and liver injury. Our study aimed to investigate the protective effects of diosmin, a phlebotrophic drug with antioxidant and anti-inflammatory effects, in a liver IRI model. Forty rats were divided into 4 groups. Sham group, control group (ischemia-reperfusion), intraoperative treatment group, and preoperative treatment group. Ischemia reperfusion model was formed by clamping hepatic pedicle for a 60 minute of ischemia followed by liver reperfusion for another 90 minutes. Superoxide dismutase (SOD) and catalase (CAT) were measured as antioaxidant enzymes in the liver tissues, and malondialdehyde (MDA) as oxidative stress marker, xanthine oxidase (XO) as an oxidant enzyme and glutathione peroxidase (GSH-Px) as antioaxidant enzyme were measured in the liver tissues and the plasma samples. Hepatic function tests were lower in treatment groups than control group (p<0.001 for ALT and AST). Plasma XO and MDA levels were lower in treatment groups than control group, but plasma GSH-Px levels were higher (p<0.05 for all). Tissue MDA levels were lower in treatment groups than control group, but tissue GSH-Px, SOD, CAT and XO levels were higher (p<0.05 for MDA and p<0.001 for others). Samples in control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. It has been found that both preoperative and intraoperative diosmin treatment decreases cellular damage and protects cells from toxic effects in liver IRI. As a conclusion, diosmin may be used as a protective agent against IRI in elective and emergent liver surgical operations. PMID:24289756

Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

PubMed Central

Hooper, Pamela J.; Chu, Brian K.; Mikhailov, Alexei; Ottesen, Eric A.; Bradley, Mark

2014-01-01

Background In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF. Methodology/Principal Findings To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012. Conclusions/Significance Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal. PMID:25411843

A satellite-driven, client-server hydro-economic model prototype for agricultural water management

NASA Astrophysics Data System (ADS)

Maneta, Marco; Kimball, John; He, Mingzhu; Payton Gardner, W.

2017-04-01

Anticipating agricultural water demand, land reallocation, and impact on farm revenues associated with different policy or climate constraints is a challenge for water managers and for policy makers. While current integrated decision support systems based on programming methods provide estimates of farmer reaction to external constraints, they have important shortcomings such as the high cost of data collection surveys necessary to calibrate the model, biases associated with inadequate farm sampling, infrequent model updates and recalibration, model overfitting, or their deterministic nature, among other problems. In addition, the administration of water supplies and the generation of policies that promote sustainable agricultural regions depend on more than one bureau or office. Unfortunately, managers from local and regional agencies often use different datasets of variable quality, which complicates coordinated action. To overcome these limitations, we present a client-server, integrated hydro-economic modeling and observation framework driven by satellite remote sensing and other ancillary information from regional monitoring networks. The core of the framework is a stochastic data assimilation system that sequentially ingests remote sensing observations and corrects the parameters of the hydro-economic model at unprecedented spatial and temporal resolutions. An economic model of agricultural production, based on mathematical programming, requires information on crop type and extent, crop yield, crop transpiration and irrigation technology. A regional hydro-climatologic model provides biophysical constraints to an economic model of agricultural production with a level of detail that permits the study of the spatial impact of large- and small-scale water use decisions. Crop type and extent is obtained from the Cropland Data Layer (CDL), which is multi-sensor operational classification of crops maintained by the United States Department of Agriculture. Because this product is only available for the conterminous United States, the framework is currently only applicable in this region. To obtain information on crop phenology, productivity and transpiration at adequate spatial and temporal frequencies we blend high spatial resolution Landsat information with high temporal fidelity MODIS imagery. The result is a 30 m, 8-day fused dataset of crop greenness that is subsequently transformed into productivity and transpiration by adapting existing forest productivity and transpiration algorithms for agricultural applications. To ensure all involved agencies work with identical information and that end-users are sheltered from the computational burden of storing and processing remote sensing data, this modeling framework is integrated in a client-server architecture based on the Hydra platform (www.hydraplatform.org). Assimilation and processing of resource-intensive remote sensing information, as well as hydrologic and other ancillary data, occur on the server side. With this architecture, our decision support system becomes a light weight 'app' that connects to the server to retrieve the latest information regarding water demands, land use, yields and hydrologic information required to run different management scenarios. This architecture ensures that all agencies and teams involved in water management use the same, up-to-date information in their simulations.

Using crustal thickness and subsidence history on the Iberia-Newfoundland margins to constrain lithosphere deformation modes during continental breakup

NASA Astrophysics Data System (ADS)

Jeanniot, Ludovic; Kusznir, Nick; Manatschal, Gianreto; Mohn, Geoffroy

2014-05-01

Observations at magma-poor rifted margins such as Iberia-Newfoundland show a complex lithosphere deformation history during continental breakup and seafloor spreading initiation leading to complex OCT architecture with hyper-extended continental crust and lithosphere, exhumed mantle and scattered embryonic oceanic crust and continental slivers. Initiation of seafloor spreading requires both the rupture of the continental crust and lithospheric mantle, and the onset of decompressional melting. Their relative timing controls when mantle exhumation may occur; the presence or absence of exhumed mantle provides useful information on the timing of these events and constraints on lithosphere deformation modes. A single lithosphere deformation mode leading to continental breakup and sea-floor spreading cannot explain observations. We have determined the sequence of lithosphere deformation events for two profiles across the present-day conjugate Iberia-Newfoundland margins, using forward modelling of continental breakup and seafloor spreading initiation calibrated against observations of crustal basement thickness and subsidence. Flow fields, representing a sequence of lithosphere deformation modes, are generated by a 2D finite element viscous flow model (FeMargin), and used to advect lithosphere and asthenosphere temperature and material. FeMargin is kinematically driven by divergent deformation in the upper 15-20 km of the lithosphere inducing passive upwelling beneath that layer; extensional faulting and magmatic intrusions deform the topmost upper lithosphere, consistent with observations of deformation processes occurring at slow spreading ocean ridges (Cannat, 1996). Buoyancy enhanced upwelling, as predicted by Braun et al. (2000) is also kinematically included in the lithosphere deformation model. Melt generation by decompressional melting is predicted using the parameterization and methodology of Katz et al. (2003). The distribution of lithosphere deformation, the contribution of buoyancy driven upwelling and their spatial and temporal evolution including lateral migration are determined by using a series of numerical experiments, tested and calibrated against observations of crustal thicknesses and water-loaded subsidence. Pure-shear widths exert a strong control on the timing of crustal rupture and melt initiation; to satisfy OCT architecture, subsidence and mantle exhumation, we need to focus the deformation from a broad to a narrow region. The lateral migration of the deformation flow axis has an important control on the rupture of continental crust and lithosphere, melt initiation, their relative timing, the resulting OCT architecture and conjugate margin asymmetry. The numerical models are used to predict margin isostatic response and subsidence history.

Architectural Lessons: Look Back In Order To Move Forward

NASA Astrophysics Data System (ADS)

Huang, T.; Djorgovski, S. G.; Caltagirone, S.; Crichton, D. J.; Hughes, J. S.; Law, E.; Pilone, D.; Pilone, T.; Mahabal, A.

2015-12-01

True elegance of scalable and adaptable architecture is not about incorporating the latest and greatest technologies. Its elegance is measured by its ability to scale and adapt as its operating environment evolves over time. Architecture is the link that bridges people, process, policies, interfaces, and technologies. Architectural development begins by observe the relationships which really matter to the problem domain. It follows by the creation of a single, shared, evolving, pattern language, which everyone contributes to, and everyone can use [C. Alexander, 1979]. Architects are the true artists. Like all masterpieces, the values and strength of architectures are measured not by the volumes of publications, it is measured by its ability to evolve. An architect must look back in order to move forward. This talk discusses some of the prior works including onboard data analysis system, knowledgebase system, cloud-based Big Data platform, as enablers to help shape the new generation of Earth Science projects at NASA and EarthCube where a community-driven architecture is the key to enable data-intensive science. [C. Alexander, The Timeless Way of Building, Oxford University, 1979.

Bridging a divide: architecture for a joint hospital-primary care data warehouse.

PubMed

An, Jeff; Keshavjee, Karim; Mirza, Kashif; Vassanji, Karim; Greiver, Michelle

2015-01-01

Healthcare costs are driven by a surprisingly small number of patients. Predicting who is likely to require care in the near future could help reduce costs by pre-empting use of expensive health care resources such as emergency departments and hospitals. We describe the design of an architecture for a joint hospital-primary care data warehouse (JDW) that can monitor the effectiveness of in-hospital interventions in reducing readmissions and predict which patients are most likely to be admitted to hospital in the near future. The design identifies the key governance elements, the architectural principles, the business case, the privacy architecture, future work flows, the IT infrastructure, the data analytics and the high level implementation plan for realization of the JDW. This architecture fills a gap in bridging data from two separate hospital and primary care organizations, not a single managed care entity with multiple locations. The JDW architecture design was well received by the stakeholders engaged and by senior leadership at the hospital and the primary care organization. Future plans include creating a demonstration system and conducting a pilot study.

Systems biology driven software design for the research enterprise.

PubMed

Boyle, John; Cavnor, Christopher; Killcoyne, Sarah; Shmulevich, Ilya

2008-06-25

In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the required software tools. We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model. By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data.

Cyberinfrastructure to Support Collaborative and Reproducible Computational Hydrologic Modeling

NASA Astrophysics Data System (ADS)

Goodall, J. L.; Castronova, A. M.; Bandaragoda, C.; Morsy, M. M.; Sadler, J. M.; Essawy, B.; Tarboton, D. G.; Malik, T.; Nijssen, B.; Clark, M. P.; Liu, Y.; Wang, S. W.

2017-12-01

Creating cyberinfrastructure to support reproducibility of computational hydrologic models is an important research challenge. Addressing this challenge requires open and reusable code and data with machine and human readable metadata, organized in ways that allow others to replicate results and verify published findings. Specific digital objects that must be tracked for reproducible computational hydrologic modeling include (1) raw initial datasets, (2) data processing scripts used to clean and organize the data, (3) processed model inputs, (4) model results, and (5) the model code with an itemization of all software dependencies and computational requirements. HydroShare is a cyberinfrastructure under active development designed to help users store, share, and publish digital research products in order to improve reproducibility in computational hydrology, with an architecture supporting hydrologic-specific resource metadata. Researchers can upload data required for modeling, add hydrology-specific metadata to these resources, and use the data directly within HydroShare.org for collaborative modeling using tools like CyberGIS, Sciunit-CLI, and JupyterHub that have been integrated with HydroShare to run models using notebooks, Docker containers, and cloud resources. Current research aims to implement the Structure For Unifying Multiple Modeling Alternatives (SUMMA) hydrologic model within HydroShare to support hypothesis-driven hydrologic modeling while also taking advantage of the HydroShare cyberinfrastructure. The goal of this integration is to create the cyberinfrastructure that supports hypothesis-driven model experimentation, education, and training efforts by lowering barriers to entry, reducing the time spent on informatics technology and software development, and supporting collaborative research within and across research groups.

HYDRA: A Middleware-Oriented Integrated Architecture for e-Procurement in Supply Chains

NASA Astrophysics Data System (ADS)

Alor-Hernandez, Giner; Aguilar-Lasserre, Alberto; Juarez-Martinez, Ulises; Posada-Gomez, Ruben; Cortes-Robles, Guillermo; Garcia-Martinez, Mario Alberto; Gomez-Berbis, Juan Miguel; Rodriguez-Gonzalez, Alejandro

The Service-Oriented Architecture (SOA) development paradigm has emerged to improve the critical issues of creating, modifying and extending solutions for business processes integration, incorporating process automation and automated exchange of information between organizations. Web services technology follows the SOA's principles for developing and deploying applications. Besides, Web services are considered as the platform for SOA, for both intra- and inter-enterprise communication. However, an SOA does not incorporate information about occurring events into business processes, which are the main features of supply chain management. These events and information delivery are addressed in an Event-Driven Architecture (EDA). Taking this into account, we propose a middleware-oriented integrated architecture that offers a brokering service for the procurement of products in a Supply Chain Management (SCM) scenario. As salient contributions, our system provides a hybrid architecture combining features of both SOA and EDA and a set of mechanisms for business processes pattern management, monitoring based on UML sequence diagrams, Web services-based management, event publish/subscription and reliable messaging service.

Leaf-architectured 3D Hierarchical Artificial Photosynthetic System of Perovskite Titanates Towards CO2 Photoreduction Into Hydrocarbon Fuels

PubMed Central

Zhou, Han; Guo, Jianjun; Li, Peng; Fan, Tongxiang; Zhang, Di; Ye, Jinhua

2013-01-01

The development of an “artificial photosynthetic system” (APS) having both the analogous important structural elements and reaction features of photosynthesis to achieve solar-driven water splitting and CO2 reduction is highly challenging. Here, we demonstrate a design strategy for a promising 3D APS architecture as an efficient mass flow/light harvesting network relying on the morphological replacement of a concept prototype-leaf's 3D architecture into perovskite titanates for CO2 photoreduction into hydrocarbon fuels (CO and CH4). The process uses artificial sunlight as the energy source, water as an electron donor and CO2 as the carbon source, mimicking what real leaves do. To our knowledge this is the first example utilizing biological systems as “architecture-directing agents” for APS towards CO2 photoreduction, which hints at a more general principle for APS architectures with a great variety of optimized biological geometries. This research would have great significance for the potential realization of global carbon neutral cycle. PMID:23588925

GASB and Its New Financial Reporting Model.

ERIC Educational Resources Information Center

Bean, David R.

1998-01-01

The Governmental Accounting Standards Board (GASB) recently crafted a new dual-perspective financial reporting model. In their tentative conclusions concerning model elements, the board started with the new management's discussion and analysis (MD&A) letter, continued with the new entrywide statements, and then moved to the more familiar…

MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma

PubMed Central

Wang, Lu-Kai; Pan, Szu-Hua; Chang, Yih-Leong; Hung, Pei-Fang; Kao, Shih-Han; Wang, Wen-Lung; Lin, Ching-Wen; Yang, Shuenn-Chen; Liang, Chen-Hsien; Wu, Chen-Tu; Hsiao, Tzu-Hung

2016-01-01

Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis. PMID:26561205

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

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

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

DOE PAGES

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.; ...

2016-05-04

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.

PubMed

Talukdar, Sarmistha; Pradhan, Anjan K; Bhoopathi, Praveen; Shen, Xue-Ning; August, Laura A; Windle, Jolene J; Sarkar, Devanand; Furnari, Frank B; Cavenee, Webster K; Das, Swadesh K; Emdad, Luni; Fisher, Paul B

2018-05-14

Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP). When MDA-9 is suppressed, GSCs undergo autophagic death supporting the hypothesis that MDA-9 regulates protective autophagy in GSCs under anoikis conditions. MDA-9 maintains protective autophagy through phosphorylation of BCL2 and by suppressing high levels of autophagy through EGFR signaling. MDA-9 promotes these changes by modifying FAK and PKC signaling. Gain-of-function and loss-of-function genetic approaches demonstrate that MDA-9 regulates pEGFR and pBCL2 expression through FAK and pPKC. EGFR signaling inhibits autophagy markers (ATG5, Lamp1, LC3B), helping to maintain protective autophagy, and along with pBCL2 maintain survival of GSCs. In the absence of MDA-9, this protective mechanism is deregulated; EGFR no longer maintains protective autophagy, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. In addition, pBCL2 is down-regulated in the absence of MDA-9, leading to cell death in GSCs under conditions of anoikis. Our studies confirm a functional link between MDA-9 expression and protective autophagy in GSCs and show that inhibition of MDA-9 reverses protective autophagy and induces anoikis and cell death in GSCs.

Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants

PubMed Central

Pan, C-H; Chan, C-C; Huang, Y-L; Wu, K-Y

2008-01-01

Objectives: To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. Methods: The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. Results: Summed particulate PAH levels in kitchens (median 23.9 ng/m3) were significantly higher than those in dining areas (median 4.9 ng/m3). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) μmol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) μmol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p<0.05). Furthermore, urinary MDA levels were significantly associated with urinary 1-OHP levels (p<0.001) and working hours per day (p<0.05). Conclusions: These findings indicate that urinary 1-OHP and MDA levels reflect occupational exposure to PAHs from COFs and oxidative stress in workers in Chinese restaurants. PMID:18940956

Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants.

PubMed

Pan, C-H; Chan, C-C; Huang, Y-L; Wu, K-Y

2008-11-01

To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. Summed particulate PAH levels in kitchens (median 23.9 ng/m(3)) were significantly higher than those in dining areas (median 4.9 ng/m(3)). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) mumol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) mumol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p<0.05). Furthermore, urinary MDA levels were significantly associated with urinary 1-OHP levels (p<0.001) and working hours per day (p<0.05). These findings indicate that urinary 1-OHP and MDA levels reflect occupational exposure to PAHs from COFs and oxidative stress in workers in Chinese restaurants.

The prophylactic effect of vitamin C on induced oxidative stress in rat testis following exposure to 900 MHz radio frequency wave generated by a BTS antenna model.

PubMed

Jelodar, Gholamali; Nazifi, Saeed; Akbari, Abolfazl

2013-09-01

Radio frequency wave (RFW) generated by base transceiver station (BTS) has been reported to make deleterious effects on reproduction, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW generated by BTS on oxidative stress in testis and the prophylactic effect of vitamin C by measuring the antioxidant enzymes activity, including glutathione peroxidase, superoxide dismutase (SOD) and catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: sham, sham+vitamin C (l-ascorbic acid 200 mg/kg of body weight/day by gavage), RFW (exposed to 900 MHz RFW) 'sham' and 'RFW' animals were given the vehicle, i.e., distilled water and the RFW+vitamin C group (received vitamin C in addition to exposure to RFW). At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of antioxidant enzymes and MDA activity. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p < 0.05). In the treated group, vitamin C improved antioxidant enzymes activity and reduced MDA compared with the test group (p < 0.05). It can be concluded that RFW causes oxidative stress in testis and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Development and evaluation of SOA-based AAL services in real-life environments: a case study and lessons learned.

PubMed

Stav, Erlend; Walderhaug, Ståle; Mikalsen, Marius; Hanke, Sten; Benc, Ivan

2013-11-01

The proper use of ICT services can support seniors in living independently longer. While such services are starting to emerge, current proprietary solutions are often expensive, covering only isolated parts of seniors' needs, and lack support for sharing information between services and between users. For developers, the challenge is that it is complex and time consuming to develop high quality, interoperable services, and new techniques are needed to simplify the development and reduce the development costs. This paper provides the complete view of the experiences gained in the MPOWER project with respect to using model-driven development (MDD) techniques for Service Oriented Architecture (SOA) system development in the Ambient Assisted Living (AAL) domain. To address this challenge, the approach of the European research project MPOWER (2006-2009) was to investigate and record the user needs, define a set of reusable software services based on these needs, and then implement pilot systems using these services. Further, a model-driven toolchain covering key development phases was developed to support software developers through this process. Evaluations were conducted both on the technical artefacts (methodology and tools), and on end user experience from using the pilot systems in trial sites. The outcome of the work on the user needs is a knowledge base recorded as a Unified Modeling Language (UML) model. This comprehensive model describes actors, use cases, and features derived from these. The model further includes the design of a set of software services, including full trace information back to the features and use cases motivating their design. Based on the model, the services were implemented for use in Service Oriented Architecture (SOA) systems, and are publicly available as open source software. The services were successfully used in the realization of two pilot applications. There is therefore a direct and traceable link from the user needs of the elderly, through the service design knowledge base, to the service and pilot implementations. The evaluation of the SOA approach on the developers in the project revealed that SOA is useful with respect to job performance and quality. Furthermore, they think SOA is easy to use and support development of AAL applications. An important finding is that the developers clearly report that they intend to use SOA in the future, but not for all type of projects. With respect to using model-driven development in web services design and implementation, the developers reported that it was useful. However, it is important that the code generated from the models is correct if the full potential of MDD should be achieved. The pilots and their evaluation in the trial sites showed that the services of the platform are sufficient to create suitable systems for end users in the domain. A SOA platform with a set of reusable domain services is a suitable foundation for more rapid development and tailoring of assisted living systems covering reoccurring needs among elderly users. It is feasible to realize a tool-chain for model-driven development of SOA applications in the AAL domain, and such a tool-chain can be accepted and found useful by software developers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The influence of foreign vs. North American emissions on surface ozone in the US

NASA Astrophysics Data System (ADS)

Reidmiller, D. R.; Fiore, A. M.; Jaffe, D. A.; Bergmann, D.; Cuvelier, C.; Dentener, F. J.; Duncan, B. N.; Folberth, G.; Gauss, M.; Gong, S.; Hess, P.; Jonson, J. E.; Keating, T.; Lupu, A.; Marmer, E.; Park, R.; Schultz, M. G.; Shindell, D. T.; Szopa, S.; Vivanco, M. G.; Wild, O.; Zuber, A.

2009-07-01

As part of the Hemispheric Transport of Air Pollution (HTAP; http:// www.htap.org) project, we analyze results from 15 global and 1 hemispheric chemical transport models and compare these to Clean Air Status and Trends Network (CASTNet) observations in the United States (US) for 2001. Using the policy-relevant maximum daily 8-h average ozone (MDA8 O3) statistic, the multi-model ensemble represents the observations well (mean r2=0.57, ensemble bias = +4.1 ppbv for all US regions and all seasons) despite a wide range in the individual model results. Correlations are strongest in the northeastern US during spring and fall (r2=0.68); and weakest in the midwestern US in summer (r2=0.46). However, large positive mean biases exist during summer for all eastern US regions, ranging from 10-20 ppbv, and a smaller negative bias is present in the western US during spring (~3 ppbv). In nearly all other regions and seasons, the biases of the model ensemble simulations are ≤5 ppbv. Sensitivity simulations in which anthropogenic O3-precursor emissions (NOx + NMVOC + CO + aerosols) were decreased by 20% in four source regions: East Asia (EA), South Asia (SA), Europe (EU) and North America (NA) show that the greatest response of MDA8 O3 to the summed foreign emissions reductions occurs during spring in the West (0.9 ppbv reduction due to 20% emissions reductions from EA + SA + EU). East Asia is the largest contributor to MDA8 O3 at all ranges of the O3 distribution for most regions (typically ~0.45 ppbv) followed closely by Europe. The exception is in the northeastern US where emissions reductions in EU had a slightly greater influence than EA emissions, particularly in the middle of the MDA8 O3 distribution (response of ~0.35 ppbv between 35-55 ppbv). EA and EU influences are both far greater (about 4x) than that from SA in all regions and seasons. In all regions and seasons O3-precursor emissions reductions of 20% in the NA source region decrease MDA8 O3 the most - by a factor of 2 to nearly 10 relative to foreign emissions reductions. The O3 response to anthropogenic NA emissions is greatest in the eastern US during summer at the high end of the O3 distribution (5-6 ppbv for 20% reductions). While the impact of foreign emissions on surface O3 in the US is not negligible - and is of increasing concern given the recent growth in Asian emissions - domestic emissions reductions remain a far more effective means of decreasing MDA8 O3 values, particularly those above 75 ppb (the current US standard).

Honey reduces blood alcohol concentration but not affects the level of serum MDA and GSH-Px activity in intoxicated male mice models.

PubMed

Shi, Peiying; Chen, Bing; Chen, Conghai; Xu, Jingyang; Shen, Zhenhuang; Miao, Xiaoqing; Yao, Hong

2015-07-14

For a long time, honey was purportedly helpful to prevent drunkenness and relieve hangover symptoms. However, few of the assertions have experienced scientific assessment. The present study examined the effects of honey on intoxicated male mice. Low or high doses of lychee flower honey (2.19 or 4.39 g/kg body weight, respectively) were single orally administrated 30 min before the ethanol intoxication of mice, followed by recording the locomotor activity by autonomic activity instrument and observing the climbing ability after alcohol. On the other hand, 2.19 g/kg honey was single orally administrated 5 min after the ethanol intoxication of mice, followed by determining the ethanol concentration in mice blood. In addition, subacute alcoholism mice models were developed and after the treatment of 2.19 g/kg honey s.i.d for successive three days, the level of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activity were detected in the models. Both of the two doses of honey increased the autonomic activity of alcoholized mice. Furthermore, the treatment of 2.19 g/kg honey could decrease significantly the blood ethanol concentration in intoxicated mice. The anti-intoxication activity of honey could be due to the effect of the fructose contained in the honey. Meanwhile, honey could not affect the serum MDA level and GSH-Px activity in alcoholism mice models. Honey indeed possesses anti-intoxication activity.

Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study.

PubMed

Zhu, Wei; Wang, Mian; Fu, Yebo; Castro, Nathan J; Fu, Sidney W; Zhang, Lijie Grace

2015-03-01

Traditional breast cancer (BrCa) bone metastasis models contain many limitations with regards to controllability, reproducibility and flexibility of design. In this study, a novel biomimetic bone microenvironment was created by integrating hydroxyapatite (HA) and native bioactive factors deposited by osteogenic induction of human bone marrow mesenchymal stem cells (MSCs) within a cytocompatible chitosan hydrogel. It was found that a 10% nanocrystalline HA (nHA) chitosan scaffold exhibited the highest BrCa adhesion and proliferation when compared to chitosan scaffolds with 20% nHA, 10% and 20% microcrystalline HA as well as amorphous HA. This 3-D tunable bone scaffold can provide a biologically relevant environment, increase cell-cell and cell-matrix interactions as found in native bone, and retain the behavior of BrCa cells with different metastasis potential (i.e. highly metastatic MDA-MB-231, less metastatic MCF-7 and transfected MDA-MB-231). The co-culture of MSCs and MDA-MB-231 in this bone model illustrated that MSCs have the capacity to upregulate the expression of the well-known metastasis-associated gene metadherin within BrCa cells. In summary, this study illustrates the ability of our 3-D bone model to create a biomimetic environment conducive to recapitulating the behavior of metastatic BrCa cells, making it a promising tool for in vitro BrCa cell bone metastasis study and for the discovery of potential therapeutics. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice

PubMed Central

Puchalapalli, Madhavi; Zeng, Xianke; Mu, Liang; Anderson, Aubree; Hix Glickman, Laura; Zhang, Ming; Sayyad, Megan R.; Mosticone Wangensteen, Sierra; Clevenger, Charles V.; Koblinski, Jennifer E.

2016-01-01

Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model. PMID:27662655

Modulation of gene expression using electrospun scaffolds with templated architecture.

PubMed

Karchin, A; Wang, Y-N; Sanders, J E

2012-06-01

The fabrication of biomimetic scaffolds is a critical component to fulfill the promise of functional tissue-engineered materials. We describe herein a simple technique, based on printed circuit board manufacturing, to produce novel templates for electrospinning scaffolds for tissue-engineering applications. This technique facilitates fabrication of electrospun scaffolds with templated architecture, which we defined as a scaffold's bulk mechanical properties being driven by its fiber architecture. Electrospun scaffolds with templated architectures were characterized with regard to fiber alignment and mechanical properties. Fast Fourier transform analysis revealed a high degree of fiber alignment along the conducting traces of the templates. Mechanical testing showed that scaffolds demonstrated tunable mechanical properties as a function of templated architecture. Fibroblast-seeded scaffolds were subjected to a peak strain of 3 or 10% at 0.5 Hz for 1 h. Exposing seeded scaffolds to the low strain magnitude (3%) significantly increased collagen I gene expression compared to the high strain magnitude (10%) in a scaffold architecture-dependent manner. These experiments indicate that scaffolds with templated architectures can be produced, and modulation of gene expression is possible with templated architectures. This technology holds promise for the long-term goal of creating tissue-engineered replacements with the biomechanical and biochemical make-up of native tissues. Copyright © 2012 Wiley Periodicals, Inc.

Choosing Training Delivery Media.

ERIC Educational Resources Information Center

Hybert, Peter R.

2000-01-01

Focuses on decisionmaking about delivery media, and introduces CADDI's Performance-based, Accelerated, Customer-Stakeholder-driven Training & Development(SM) (PACT) Processes for training and development (T&D). Describes the media decisions that correspond with the design three levels of PACT: Curriculum Architecture Design, Modular Curriculum…

Real-time value-driven diagnosis

NASA Technical Reports Server (NTRS)

Dambrosio, Bruce

1995-01-01

Diagnosis is often thought of as an isolated task in theoretical reasoning (reasoning with the goal of updating our beliefs about the world). We present a decision-theoretic interpretation of diagnosis as a task in practical reasoning (reasoning with the goal of acting in the world), and sketch components of our approach to this task. These components include an abstract problem description, a decision-theoretic model of the basic task, a set of inference methods suitable for evaluating the decision representation in real-time, and a control architecture to provide the needed continuing coordination between the agent and its environment. A principal contribution of this work is the representation and inference methods we have developed, which extend previously available probabilistic inference methods and narrow, somewhat, the gap between probabilistic and logical models of diagnosis.

Design of the HELICS High-Performance Transmission-Distribution-Communication-Market Co-Simulation Framework

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

Palmintier, Bryan S; Krishnamurthy, Dheepak; Top, Philip

This paper describes the design rationale for a new cyber-physical-energy co-simulation framework for electric power systems. This new framework will support very large-scale (100,000+ federates) co-simulations with off-the-shelf power-systems, communication, and end-use models. Other key features include cross-platform operating system support, integration of both event-driven (e.g. packetized communication) and time-series (e.g. power flow) simulation, and the ability to co-iterate among federates to ensure model convergence at each time step. After describing requirements, we begin by evaluating existing co-simulation frameworks, including HLA and FMI, and conclude that none provide the required features. Then we describe the design for the new layeredmore » co-simulation architecture.« less

Design of the HELICS High-Performance Transmission-Distribution-Communication-Market Co-Simulation Framework: Preprint

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

Palmintier, Bryan S; Krishnamurthy, Dheepak; Top, Philip

This paper describes the design rationale for a new cyber-physical-energy co-simulation framework for electric power systems. This new framework will support very large-scale (100,000+ federates) co-simulations with off-the-shelf power-systems, communication, and end-use models. Other key features include cross-platform operating system support, integration of both event-driven (e.g. packetized communication) and time-series (e.g. power flow) simulation, and the ability to co-iterate among federates to ensure model convergence at each time step. After describing requirements, we begin by evaluating existing co-simulation frameworks, including HLA and FMI, and conclude that none provide the required features. Then we describe the design for the new layeredmore » co-simulation architecture.« less

Cell Motility and Jamming across the EMT

NASA Astrophysics Data System (ADS)

Grosser, Steffen; Oswald, Linda; Lippoldt, Jürgen; Heine, Paul; Kaes, Josef A.

We use single-cell tracking and cell shape analysis to highlight the different roles that cell jamming plays in the behaviour of epithelial vs. mesenchymal mammary breast cell lines (MCF-10A, MDA-MB-231) in 2D adherent culture. An automatic segmentation allows for the evaluation of cell shapes, which we compare to predictions made by the self-propelled vertex (SPV) model. On top of that, we employ co-cultures to study the emerging demixing behaviour of these cell lines, demonstrating that the mesenchymal MDA-MB-231 cell line forms unjammed islands within the jammed collective.

Edaravone protects neurons in the rat substantia nigra against 6-hydroxydopamine-induced oxidative stress damage.

PubMed

Liu, Xiqi; Shao, Rushing; Li, Meng; Yang, Guofeng

2014-11-01

To investigate the mechanism of the neuroprotective effect of edaravone in substantia nigra (SN) of the 6-OHDA-induced rat model of Parkinson's disease. Animal model of Parkinson's disease was induced in male Sprague-Dawley rats by injecting 6-OHDA into the left medial forebrain bundle. Subsequently, rats were intraperitoneally injected with 0.3, 1, or 3 mg/kg of edaravone for 14 days or with 3 mg/kg edaravone for 14 days followed by 14 days of no treatment. We evaluated the effect of edaravone on the rotational and normal behavior of the rats, and on the number of tyrosine hydroxylase (TH)-positive cells, the amount of Nissl bodies, and the levels of glutathione (GSH), and malondialdehyde (MDA) in the SN. Edaravone treatment at 3 mg/kg significantly reduced apomorphine-induced rotational behavior (P < 0.01), improved the spontaneous behavior, prevented the decrease in the levels of TH-positive cells, Nissl bodies and GSH, and inhibited the increase in the levels of MDA (P < 0.05) in SN of rats with 6-OHDA-induced PD. Edaravone exerted a long-term neuroprotective effects in 6-OHDA-induced PD animal model by attenuating changes in the levels of GSH and MDA in SN, caused by oxidative stress. Edaravone prevented 6-OHDA-induced behavioral changes and de-pigmentation of SN that results from the loss of dopaminergic neurons.

Protective effect of co-administration of rosuvastatin and probucol on atherosclerosis in rats.

PubMed

Chen, Zuoyuan; Li, Shan; Zhao, Wenna; Chen, Xiuhua; Wang, Xiaxia

2014-10-01

This study aimed to study the combined effect of rosuvastatin and probucol on atherosclerosis (AS) in rats. In total, 95 male Wistar rats were divided into 5 groups: 25 in the control group (A), 25 in the model group (B), 15 in the rosuvastatin group (C), 15 in the probucol group (D), and 15 in the rosuvastatin combined probucol group (E). A high-lipid diet and vitamin D3 were administered to establish AS rat model. Groups C, D, and E received corresponding drugs. Blood lipids, oxidized low-density lipoprotein (OX-LDL), malonaldehyde (MDA), superoxide dismutase (SOD), adiponectin (APN), and vascular endothelial cadherin (VE-cadherin) were measured. Platelet endothelial cell adhesion molecule-1 (PECAM-1) was detected by immune histochemistry. In groups B-E, AS rat models were successfully constructed. In groups C-E, blood lipids, OX-LDL, VE-cadherin, MDA, PECAM-1, and intimal thickness were decreased (p < 0.01), while SOD and APN were increased (p < 0.05), compared with that in group B. Furthermore, group E had lower levels of OX-LDL, MDA, and PECAM-1 but higher levels of SOD and APN and attenuated intimal thickening compared with groups C or D (p < 0.05). Administering rosuvastatin and probucol could attenuate AS lesions through modulation of oxidative stress, PECAM-1, and APN. Both drugs might help slow the progression of AS.

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer.

PubMed

Kandil, Sahar; Prencipe, Filippo; Jones, Samuel; Hiscox, Stephen; Westwell, Andrew D

2018-01-01

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA-MB-231, BT474 and T47D). Compound 5c was identified to display an average activity of IC 50  = 23.5-31.3 μm, which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series. © 2017 John Wiley & Sons A/S.

Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer's disease rat.

PubMed

Liu, Zhi-Bin; Niu, Wen-Min; Yang, Xiao-Hang; Wang, Yuan; Wang, Wei-Gang

2010-12-01

To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05). Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

A Unified Data-Driven Approach for Programming In Situ Analysis and Visualization

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

Aiken, Alex

The placement and movement of data is becoming the key limiting factor on both performance and energy efficiency of high performance computations. As systems generate more data, it is becoming increasingly difficult to actually move that data elsewhere for post-processing, as the rate of improvements in supporting I/O infrastructure is not keeping pace. Together, these trends are creating a shift in how we think about exascale computations, from a viewpoint that focuses on FLOPS to one that focuses on data and data-centric operations as fundamental to the reasoning about, and optimization of, scientific workflows on extreme-scale architectures. The overarching goalmore » of our effort was the study of a unified data-driven approach for programming applications and in situ analysis and visualization. Our work was to understand the interplay between data-centric programming model requirements at extreme-scale and the overall impact of those requirements on the design, capabilities, flexibility, and implementation details for both applications and the supporting in situ infrastructure. In this context, we made many improvements to the Legion programming system (one of the leading data-centric models today) and demonstrated in situ analyses on real application codes using these improvements.« less

A multitasking finite state architecture for computer control of an electric powertrain

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

Burba, J.C.

1984-01-01

Finite state techniques provide a common design language between the control engineer and the computer engineer for event driven computer control systems. They simplify communication and provide a highly maintainable control system understandable by both. This paper describes the development of a control system for an electric vehicle powertrain utilizing finite state concepts. The basics of finite state automata are provided as a framework to discuss a unique multitasking software architecture developed for this application. The architecture employs conventional time-sliced techniques with task scheduling controlled by a finite state machine representation of the control strategy of the powertrain. The complexitiesmore » of excitation variable sampling in this environment are also considered.« less

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.

PubMed

Capellini, Verena Kise; Baldo, Caroline Floreoto; Celotto, Andréa Carla; Batalhão, Marcelo Eduardo; Cárnio, Evelin Capellari; Rodrigues, Alfredo José; Evora, Paulo Roberto Barbosa

2010-08-01

To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.

Reversible Self-Assembly of 3D Architectures Actuated by Responsive Polymers.

PubMed

Zhang, Cheng; Su, Jheng-Wun; Deng, Heng; Xie, Yunchao; Yan, Zheng; Lin, Jian

2017-11-29

An assembly of three-dimensional (3D) architectures with defined configurations has important applications in broad areas. Among various approaches of constructing 3D structures, a stress-driven assembly provides the capabilities of creating 3D architectures in a broad range of functional materials with unique merits. However, 3D architectures built via previous methods are simple, irreversible, or not free-standing. Furthermore, the substrates employed for the assembly remain flat, thus not involved as parts of the final 3D architectures. Herein, we report a reversible self-assembly of various free-standing 3D architectures actuated by the self-folding of smart polymer substrates with programmed geometries. The strategically designed polymer substrates can respond to external stimuli, such as organic solvents, to initiate the 3D assembly process and subsequently become the parts of the final 3D architectures. The self-assembly process is highly controllable via origami and kirigami designs patterned by direct laser writing. Self-assembled geometries include 3D architectures such as "flower", "rainbow", "sunglasses", "box", "pyramid", "grating", and "armchair". The reported self-assembly also shows wide applicability to various materials including epoxy, polyimide, laser-induced graphene, and metal films. The device examples include 3D architectures integrated with a micro light-emitting diode and a flex sensor, indicting the potential applications in soft robotics, bioelectronics, microelectromechanical systems, and others.

Malondialdehyde-Derived Epitopes In Human Skin Result From Acute Exposure To Solar UV And Occur In Nonmelanoma Skin Cancer Tissue

PubMed Central

Williams, Joshua D.; Bermudez, Yira; Park, Sophia L.; Stratton, Steven P.; Uchida, Koji; Hurst, Craig A.; Wondrak, Georg T.

2014-01-01

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

PubMed

Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections

PubMed Central

2014-01-01

Melanoma differentiation-associated gene 5 (MDA5) is an important intracellular receptor that recognizes long molecules of viral double-stranded RNA in innate immunity. To understand the mechanism of duck MDA5-mediated innate immunity, we cloned the MDA5 cDNA from the Muscovy duck (Cairina moschata). Quantitative real-time PCR analysis indicates that duck MDA5 mRNA was constitutively expressed in all sampled tissues. A significant increase of MDA5 mRNA was detected in the brain, spleen and lungs of ducks after infection with an H5N1 highly pathogenic avian influenza virus (HPAIV). We investigated the role of the predicted functional domains of MDA5. The results indicate the caspase activation and recruitment domain (CARD) of duck MDA5 had a signal transmission function through IRF-7-dependent signaling pathway. Overexpression of the CARD strongly activated the chicken IFN-β promoter and upregulated the mRNA expression of antiviral molecules (such as OAS, PKR and Mx), proinflammatory cytokines (such as IL-2, IL-6, IFN-α and IFN-γ, but not IL-1β and IL-8) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) (RIG-I and LGP2) without exogenous stimulation. We also demonstrate the NS1 of the H5N1 HPAIV inhibited the duck MDA5-mediated signaling pathway in vitro. These results suggest that duck MDA5 is an important receptor for inducing antiviral activity in the host immune response of ducks. PMID:24939427

How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis.

PubMed

Kastner, Randee J; Sicuri, Elisa; Stone, Christopher M; Matwale, Gabriel; Onapa, Ambrose; Tediosi, Fabrizio

2017-09-01

Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.

A Modular, Data Driven System: Architecture for GSFC Ground Systems: GSFC's Mission Services Evolution Center (GMSEC)

NASA Technical Reports Server (NTRS)

Cary, Everett; Smith, Danford

2004-01-01

The GSFC Mission Services Evolution Center (GMSEC) was established in 2001 to coordinate ground and flight data systems development and services at NASA's Goddard Space Flight Center (GSFC). GMSEC system architecture represents a new way to build the next generation systems to be used for a variety of missions for years to come. The old approach was to find or build the best products available and integrate them into a reusable system to meet everyone's needs. The new approach assumes that needs, products, and technology will change.

Sensitive and selective quantification of free and total malondialdehyde in plasma using UHPLC-HRMS.

PubMed

Mendonça, Rute; Gning, Ophélie; Di Cesaré, Claudia; Lachat, Laurence; Bennett, Nigel C; Helfenstein, Fabrice; Glauser, Gaétan

2017-09-01

Quantification of malondialdehyde (MDA) as a marker of lipid peroxidation is relevant for many research fields. We describe a new sensitive and selective method to measure free and total plasmatic MDA using derivatization with 2,4-dinitrophenylhydrazine (DNPH) and ultra-HPLC-high-resolution MS. Free and total MDA were extracted from minute sample amounts (10 μl) using acidic precipitation and alkaline hydrolysis followed by acidic precipitation, respectively. Derivatization was completed within 10 min at room temperature, and the excess DNPH discarded by liquid-liquid extraction. Quantification was achieved by internal standardization using dideuterated MDA as internal standard. The method's lowest limit of quantification was 100 nM and linearity spanned greater than three orders of magnitude. Intra- and inter-day precisions for total MDA were 2.9% and 3.0%, respectively, and those for free MDA were 12.8% and 24.9%, respectively. Accuracy was 101% and 107% at low and high concentrations, respectively. In human plasma, free MDA levels were 120 nM (SD 36.26) and total MDA levels were 6.7 μM (SD 0.46). In addition, we show the applicability of this method to measure MDA plasma levels from a variety of animal species, making it invaluable to scientists in various fields. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Improved quantification of a commercial enzyme-linked immunosorbent assay kit for measuring anti-MDA5 antibody.

PubMed

Gono, Takahisa; Okazaki, Yuka; Murakami, Akihiro; Kuwana, Masataka

2018-04-09

To compare the quantitative performance for measuring anti-MDA5 antibody titer of two enzyme-linked immunosorbent assay (ELISA) systems: an in-house ELISA and the commercial MESACUP TM anti-MDA5 test. Anti-MDA5 antibody titer was measured in sera from 70 patients with dermatomyositis using an in-house ELISA and the MESACUP TM anti-MDA5 test side-by-side. For the commercial ELISA kit, serum samples diluted 1:101 were used according to the manufacturer's protocol, but serial dilutions of sera were also examined to identify the optimal serum dilution for quantification. The anti-MDA5 antibody titers measured by the in-house and commercial ELISAs were positively correlated with each other (r = 0.53, p = .0001), but the antibody titer measured by the commercial ELISA was less sensitive to change after medical treatment, and 37 (80%) of 46 anti-MDA5-positive sera had antibody titer exceeding the quantification range specified by the manufacturer (≥150 index). Experiments using diluted serum samples revealed that diluting the sera 1:5050 improved the quantitative performance of the MESACUP TM anti-MDA5 test, including a better correlation with the in-house ELISA results and an increased sensitivity to change. We improved the ability of the commercial ELISA kit to quantify anti-MDA5 antibody titer by altering its protocol.

Impregnating magnetic components with MDA free epoxy

NASA Astrophysics Data System (ADS)

Sanchez, R. O.; Domeier, L.; Gunewardena, S.

1995-08-01

This paper describes the use of 'Formula 456' an aliphatic amine cured epoxy for impregnating coils. Methylene dianiline (MDA) has been used for more than 20 years as the curing agent for various epoxy formulations throughout the Department of Energy. Sandia National Laboratories began the process of replacing MDA with other formulations because of regulations imposed by OSHA on the use of MDA.

Molecular Structure of a 9-MDa Icosahedral Pyruvate Dehydrogenase Subcomplex Containing the E2 and E3 Enzymes Using Cryoelectron Microscopy*

PubMed Central

Milne, Jacqueline L. S.; Wu, Xiongwu; Borgnia, Mario J.; Lengyel, Jeffrey S.; Brooks, Bernard R.; Shi, Dan; Perham, Richard N.; Subramaniam, Sriram

2006-01-01

The pyruvate dehydrogenase multienzyme complexes are among the largest multifunctional catalytic machines in cells, catalyzing the production of acetyl CoA from pyruvate. We have previously reported the molecular architecture of an 11-MDa subcomplex comprising the 60-mer icosahedral dihydrolipoyl acetyltransferase (E2) decorated with 60 copies of the heterotetrameric (α2β2) 153-kDa pyruvate decarboxylase (E1) from Bacillus stearothermophilus (Milne, J. L. S., Shi, D., Rosenthal, P. B., Sunshine, J. S., Domingo, G. J., Wu, X., Brooks, B. R., Perham, R. N., Henderson, R., and Subramaniam, S. (2002) EMBO J. 21, 5587–5598). An annular gap of ~90 Å separates the acetyltransferase catalytic domains of the E2 from an outer shell formed of E1 tetramers. Using cryoelectron microscopy, we present here a three-dimensional reconstruction of the E2 core decorated with 60 copies of the homodimeric 100-kDa dihydrolipoyl dehydrogenase (E3). The E2E3 complex has a similar annular gap of ~75 Å between the inner icosahedral assembly of acetyltransferase domains and the outer shell of E3 homodimers. Automated fitting of the E3 coordinates into the map suggests excellent correspondence between the density of the outer shell map and the positions of the two best fitting orientations of E3. As in the case of E1 in the E1E2 complex, the central 2-fold axis of the E3 homodimer is roughly oriented along the periphery of the shell, making the active sites of the enzyme accessible from the annular gap between the E2 core and the outer shell. The similarities in architecture of the E1E2 and E2E3 complexes indicate fundamental similarities in the mechanism of active site coupling involved in the two key stages requiring motion of the swinging lipoyl domain across the annular gap, namely the synthesis of acetyl CoA and regeneration of the dithiolane ring of the lipoyl domain. PMID:16308322

[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].

PubMed

Wang, Le; Mi, Chengrong; Wang, Wen

2015-06-16

To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses. Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination. ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node. The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.

An asynchronous data-driven readout prototype for CEPC vertex detector

NASA Astrophysics Data System (ADS)

Yang, Ping; Sun, Xiangming; Huang, Guangming; Xiao, Le; Gao, Chaosong; Huang, Xing; Zhou, Wei; Ren, Weiping; Li, Yashu; Liu, Jianchao; You, Bihui; Zhang, Li

2017-12-01

The Circular Electron Positron Collider (CEPC) is proposed as a Higgs boson and/or Z boson factory for high-precision measurements on the Higgs boson. The precision of secondary vertex impact parameter plays an important role in such measurements which typically rely on flavor-tagging. Thus silicon CMOS Pixel Sensors (CPS) are the most promising technology candidate for a CEPC vertex detector, which can most likely feature a high position resolution, a low power consumption and a fast readout simultaneously. For the R&D of the CEPC vertex detector, we have developed a prototype MIC4 in the Towerjazz 180 nm CMOS Image Sensor (CIS) process. We have proposed and implemented a new architecture of asynchronous zero-suppression data-driven readout inside the matrix combined with a binary front-end inside the pixel. The matrix contains 128 rows and 64 columns with a small pixel pitch of 25 μm. The readout architecture has implemented the traditional OR-gate chain inside a super pixel combined with a priority arbiter tree between the super pixels, only reading out relevant pixels. The MIC4 architecture will be introduced in more detail in this paper. It will be taped out in May and will be characterized when the chip comes back.

Data-driven sampling method for building 3D anatomical models from serial histology

NASA Astrophysics Data System (ADS)

Salunke, Snehal Ulhas; Ablove, Tova; Danforth, Theresa; Tomaszewski, John; Doyle, Scott

2017-03-01

In this work, we investigate the effect of slice sampling on 3D models of tissue architecture using serial histopathology. We present a method for using a single fully-sectioned tissue block as pilot data, whereby we build a fully-realized 3D model and then determine the optimal set of slices needed to reconstruct the salient features of the model objects under biological investigation. In our work, we are interested in the 3D reconstruction of microvessel architecture in the trigone region between the vagina and the bladder. This region serves as a potential avenue for drug delivery to treat bladder infection. We collect and co-register 23 serial sections of CD31-stained tissue images (6 μm thick sections), from which four microvessels are selected for analysis. To build each model, we perform semi-automatic segmentation of the microvessels. Subsampled meshes are then created by removing slices from the stack, interpolating the missing data, and re-constructing the mesh. We calculate the Hausdorff distance between the full and subsampled meshes to determine the optimal sampling rate for the modeled structures. In our application, we found that a sampling rate of 50% (corresponding to just 12 slices) was sufficient to recreate the structure of the microvessels without significant deviation from the fullyrendered mesh. This pipeline effectively minimizes the number of histopathology slides required for 3D model reconstruction, and can be utilized to either (1) reduce the overall costs of a project, or (2) enable additional analysis on the intermediate slides.

Comparison of protective effects of safflor injection and extract of Ginkgo biloba on lung ischemia/reperfusion injury in rabbits.

PubMed

Tian, Xiao-xi; Wang, Bo-liang; Cao, Yi-zhan; Zhong, Yue-xia; Tu, Yan-yang; Xiao, Jian-bo; He, Qian-feng; Zhai, Li-na

2015-03-01

To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism. In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC). In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05). SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.

[Protective effects of astaxanthin against oxidative damage induced by 60Co gamma-ray irradiation].

PubMed

Zhao, Wei; Jing, Xuejun; Chen, Chen; Cui, Jie; Yang, Mo; Zhang, Zunzhen

2011-09-01

To investigate the protection effect of haematococcus pluvialis (containing astaxanthin) against the impairment of anti-oxidative system and DNA damage in mice induced by 60Co gamma-rays. Fifty mice were randomly divided into five groups, i.e. three haematococcus pluvialis groups (41.7, 83.3 and 166.7 mg/kg in vegetable oil, respectively), control group and model group (vegetable oil only). All mice except control group were irradiated by 8 Gy 60Co gamma-rays 30 days later, and executed in the 4th day after irradiation. Liver cells were collected for the analysis of the integrity of DNA by comet assay, as well as MDA contents, SOD and GSH-Px activities in liver by commercial kits. Peripheral granulocyte and bone marrow nucleated cells were counted by hematocyte counter. MDA contents of model group were higher than those of control group (P < 0.01), and SOD, GSH-Px activities of model group were lower than those of control group (P < 0.01). Compared with the model group, MDA contents were decreased (P < 0.01), and SOD and GSH-Px activities were increased (P < 0.01) in all haematococcus pluvialis groups, especially in the high haematococcus pluvialis group, and the more haematococcus pluvialis in the diet of mice, the lower rate of comet tail and OTM value were shown (P < 0.01). Furthermore, the counts of peripheral granulocyte and bone marrow nucleated cells of model group were lower than those of the control group, while the counts of peripheral granulocyte and bone marrow nucleated cells of medium and high haematococcus pluvialis groups were increased significantly when compared with the model group (P < 0.01). Astaxanthin might have some protective effect against oxidative impairment and DNA damage induced by 60Co gamma-rays in mice.

Paramyxovirus V protein interaction with the antiviral sensor LGP2 disrupts MDA5 signaling enhancement but is not relevant to LGP2-mediated RLR signaling inhibition.

PubMed

Rodriguez, Kenny R; Horvath, Curt M

2014-07-01

The interferon antiviral system is a primary barrier to virus replication triggered upon recognition of nonself RNAs by the cytoplasmic sensors encoded by retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology gene 2 (LGP2). Paramyxovirus V proteins are interferon antagonists that can selectively interact with MDA5 and LGP2 through contact with a discrete helicase domain region. Interaction with MDA5, an activator of antiviral signaling, disrupts interferon gene expression and antiviral responses. LGP2 has more diverse reported roles as both a coactivator of MDA5 and a negative regulator of both RIG-I and MDA5. This functional dichotomy, along with the concurrent interference with both cellular targets, has made it difficult to assess the unique consequences of V protein interaction with LGP2. To directly evaluate the impact of LGP2 interference, MDA5 and LGP2 variants unable to be recognized by measles virus and parainfluenza virus 5 (PIV5) V proteins were tested in signaling assays. Results indicate that interaction with LGP2 specifically prevents coactivation of MDA5 signaling and that LGP2's negative regulatory capacity was not affected. V proteins only partially antagonize RIG-I at high concentrations, and their expression had no additive effects on LGP2-mediated negative regulation. However, conversion of RIG-I to a direct V protein target was accomplished by only two amino acid substitutions that allowed both V protein interaction and efficient interference. These results clarify the unique consequences of MDA5 and LGP2 interference by paramyxovirus V proteins and help resolve the distinct roles of LGP2 in both activation and inhibition of antiviral signal transduction. Importance: Paramyxovirus V proteins interact with two innate immune receptors, MDA5 and LGP2, but not RIG-I. V proteins prevent MDA5 from signaling to the beta interferon promoter, but the consequences of LGP2 targeting are poorly understood. As the V protein targets MDA5 and LGP2 simultaneously, and LGP2 is both a positive and negative regulator of both MDA5 and RIG-I, it has been difficult to evaluate the specific advantages conferred by LGP2 targeting. Experiments with V-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5. LGP2's negative regulation of MDA5 and RIG-I remains intact irrespective of V protein interaction. Complementary experiments demonstrate that RIG-I can be converted to V protein sensitivity by two amino acid substitutions. These findings clarify the functions of LGP2 as a positive regulator of MDA5 signaling, demonstrate the basis for V-mediated LGP2 targeting, and broaden our understanding of paramyxovirus-host interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Paramyxovirus V Protein Interaction with the Antiviral Sensor LGP2 Disrupts MDA5 Signaling Enhancement but Is Not Relevant to LGP2-Mediated RLR Signaling Inhibition

PubMed Central

Rodriguez, Kenny R.

2014-01-01

ABSTRACT The interferon antiviral system is a primary barrier to virus replication triggered upon recognition of nonself RNAs by the cytoplasmic sensors encoded by retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology gene 2 (LGP2). Paramyxovirus V proteins are interferon antagonists that can selectively interact with MDA5 and LGP2 through contact with a discrete helicase domain region. Interaction with MDA5, an activator of antiviral signaling, disrupts interferon gene expression and antiviral responses. LGP2 has more diverse reported roles as both a coactivator of MDA5 and a negative regulator of both RIG-I and MDA5. This functional dichotomy, along with the concurrent interference with both cellular targets, has made it difficult to assess the unique consequences of V protein interaction with LGP2. To directly evaluate the impact of LGP2 interference, MDA5 and LGP2 variants unable to be recognized by measles virus and parainfluenza virus 5 (PIV5) V proteins were tested in signaling assays. Results indicate that interaction with LGP2 specifically prevents coactivation of MDA5 signaling and that LGP2's negative regulatory capacity was not affected. V proteins only partially antagonize RIG-I at high concentrations, and their expression had no additive effects on LGP2-mediated negative regulation. However, conversion of RIG-I to a direct V protein target was accomplished by only two amino acid substitutions that allowed both V protein interaction and efficient interference. These results clarify the unique consequences of MDA5 and LGP2 interference by paramyxovirus V proteins and help resolve the distinct roles of LGP2 in both activation and inhibition of antiviral signal transduction. IMPORTANCE Paramyxovirus V proteins interact with two innate immune receptors, MDA5 and LGP2, but not RIG-I. V proteins prevent MDA5 from signaling to the beta interferon promoter, but the consequences of LGP2 targeting are poorly understood. As the V protein targets MDA5 and LGP2 simultaneously, and LGP2 is both a positive and negative regulator of both MDA5 and RIG-I, it has been difficult to evaluate the specific advantages conferred by LGP2 targeting. Experiments with V-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5. LGP2's negative regulation of MDA5 and RIG-I remains intact irrespective of V protein interaction. Complementary experiments demonstrate that RIG-I can be converted to V protein sensitivity by two amino acid substitutions. These findings clarify the functions of LGP2 as a positive regulator of MDA5 signaling, demonstrate the basis for V-mediated LGP2 targeting, and broaden our understanding of paramyxovirus-host interactions. PMID:24829334

p62 Regulates the Proliferation of Molecular Apocrine Breast Cancer Cells

PubMed Central

Nozaki, Fumi; Hirotani, Yukari; Nakanishi, Yoko; Yamaguchi, Hiromi; Nishimaki, Haruna; Noda, Hiroko; Tang, Xiaoyan; Yamamoto, Hisae; Suzuki, Atsuko; Seki, Toshimi; Masuda, Shinobu

2016-01-01

p62, also called sequestosome 1 (SQSTM1), is a multifunctional signaling molecule that affects cell proliferation. Recently, we found accumulation of p62 in apocrine carcinoma of the breast, however, the biological role of p62 expression in apocrine carcinoma still remains unclear. To investigate whether p62 might contribute to tumor cell proliferation in apocrine carcinomas, we used the MDA-MB-453 (androgen receptor-positive, HER2-type) and MFM223 (androgen receptor-positive, triple-negative type) breast cancer cell lines as models of molecular apocrine carcinoma. Both MDA-MB-453 and MFM223 showed strong and d high p62 protein expression than MCF7 cells (androgen receptor-negative, luminal A type). Knockdown of p62 resulted in significant reduction of the cell proliferative activity in both MDA-MB-453 (P<0.01) and MFM223 (P<0.05). In conclusion, p62 could contribute to cell proliferation and represent a therapeutic target in apocrine carcinoma. PMID:27682016

p62 Regulates the Proliferation of Molecular Apocrine Breast Cancer Cells.

PubMed

Nozaki, Fumi; Hirotani, Yukari; Nakanishi, Yoko; Yamaguchi, Hiromi; Nishimaki, Haruna; Noda, Hiroko; Tang, Xiaoyan; Yamamoto, Hisae; Suzuki, Atsuko; Seki, Toshimi; Masuda, Shinobu

2016-08-30

p62, also called sequestosome 1 (SQSTM1), is a multifunctional signaling molecule that affects cell proliferation. Recently, we found accumulation of p62 in apocrine carcinoma of the breast, however, the biological role of p62 expression in apocrine carcinoma still remains unclear. To investigate whether p62 might contribute to tumor cell proliferation in apocrine carcinomas, we used the MDA-MB-453 (androgen receptor-positive, HER2-type) and MFM223 (androgen receptor-positive, triple-negative type) breast cancer cell lines as models of molecular apocrine carcinoma. Both MDA-MB-453 and MFM223 showed strong and d high p62 protein expression than MCF7 cells (androgen receptor-negative, luminal A type). Knockdown of p62 resulted in significant reduction of the cell proliferative activity in both MDA-MB-453 (P<0.01) and MFM223 (P<0.05). In conclusion, p62 could contribute to cell proliferation and represent a therapeutic target in apocrine carcinoma.

Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.

PubMed

Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang; Cukuroglu, Engin; Tran, Hoang-Dai; Göke, Jonathan; Tan, Zi Ying; Saw, Tzuen Yih; Tan, Cheng-Peow; Lokman, Hidayat; Lee, Younghwan; Kim, Donghoon; Ko, Han Seok; Kim, Seong-Oh; Park, Jae Hyeon; Cho, Nam-Joon; Hyde, Thomas M; Kleinman, Joel E; Shin, Joo Heon; Weinberger, Daniel R; Tan, Eng King; Je, Hyunsoo Shawn; Ng, Huck-Hui

2016-08-04

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving Coverage and Compliance in Mass Drug Administration for the Elimination of LF in Two ‘Endgame’ Districts in Indonesia Using Micronarrative Surveys

PubMed Central

Krentel, Alison; Damayanti, Rita; Titaley, Christiana Rialine; Suharno, Nugroho; Bradley, Mark; Lynam, Timothy

2016-01-01

Background As the Global Programme to Eliminate Lymphatic Filariasis (LF) approaches its 2020 goal, an increasing number of districts will enter the endgame phase where drug coverage rates from mass drug administration (MDA) are used to assess whether MDA can be stopped. As reported, the gap between reported and actual drug coverage in some contexts has overestimated the true rates, thus causing premature administration of transmission assessment surveys (TAS) that detect ongoing LF transmission. In these cases, districts must continue with additional rounds of MDA. Two districts in Indonesia (Agam District, Depok City) fit this criteria—one had not met the pre-TAS criteria and the other, had not passed the TAS criteria. In both cases, the district health teams needed insight into their drug delivery programs in order to improve drug coverage in the subsequent MDA rounds. Methodology/Principal Findings To inform the subsequent MDA round, a micronarrative survey tool was developed to capture community members’ experience with MDA and the social realm where drug delivery and compliance occur. A baseline survey was implemented after the 2013 MDA in endemic communities in both districts using the EPI sampling criteria (n = 806). Compliance in the last MDA was associated with perceived importance of the LF drugs for health (p<0.001); perceived safety of the LF drugs (p<0.001) and knowing someone in the household has complied (p<0.001). Results indicated that specialized messages were needed to reach women and younger men. Both districts used these recommendations to implement changes to their MDA without additional financial support. An endline survey was performed after the 2014 MDA using the same sampling criteria (n = 811). Reported compliance in the last MDA improved in both districts from 57% to 77% (p<0.05). Those who reported having ever taken the LF drug rose from 79% to 90% (p<0.001) in both sites. Conclusions/Significance Micronarrative surveys were shown to be a valid and effective tool to detect operational issues within MDA programs. District health staff felt ownership of the results, implementing feasible changes to their programs that resulted in significant improvements to coverage and compliance in the subsequent MDA. This kind of implementation research using a micronarrative survey tool could benefit underperforming MDA programs as well as other disease control programs where a deeper understanding is needed to improve healthcare delivery. PMID:27812107

The advection of microparticles, MCF-7 and MDA-MB-231 breast cancer cells in response to very low Reynolds numbers.

PubMed

Morley, Sinéad T; Walsh, Michael T; Newport, David T

2017-05-01

The lymphatic system is an extensive vascular network that serves as the primary route for the metastatic spread of breast cancer cells (BCCs). The dynamics by which BCCs travel in the lymphatics to distant sites, and eventually establish metastatic tumors, remain poorly understood. Particle tracking techniques were employed to analyze the behavior of MCF-7 and MDA-MB-231 BCCs which were exposed to lymphatic flow conditions in a 100  μ m square microchannel. The behavior of the BCCs was compared to rigid particles of various diameters (η = d p /H= 0.05-0.32) that have been used to simulate cell flow in lymph. Parabolic velocity profiles were recorded for all particle sizes. All particles were found to lag the fluid velocity, the larger the particle the slower its velocity relative to the local flow (5%-15% velocity lag recorded). A distinct difference between the behavior of BCCs and particles was recorded. The BCCs travelled approximately 40% slower than the undisturbed flow, indicating that morphology and size affects their response to lymphatic flow conditions ( Re <  1). BCCs adhered together, forming aggregates whose behavior was irregular. At lymphatic flow rates, MCF-7s were distributed uniformly across the channel in comparison to the MDA-MB-231 cells which travelled in the central region (88% of cells found within 0.35 ≤ W ≤ 0.64), indicating that metastatic MDA-MB-231 cells are subjected to a lower range of shear stresses in vivo . This suggests that both size and deformability need to be considered when modelling BCC behavior in the lymphatics. This finding will inform the development of in vitro lymphatic flow and metastasis models.

Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models

PubMed Central

Paydar, Mohammadjavad; Kamalidehghan, Behnam; Wong, Yi Li; Wong, Won Fen; Looi, Chung Yeng; Mustafa, Mohd Rais

2014-01-01

To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC50 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC50 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer. PMID:24944509

A novel taspine derivative, HMQ1611, inhibits breast cancer cell growth via estrogen receptor α and EGF receptor signaling pathways.

PubMed

Zhan, Yingzhuan; Zhang, Yanmin; Liu, Cuicui; Zhang, Jie; Smith, Wanli W; Wang, Nan; Chen, Yinnan; Zheng, Lei; He, Langchong

2012-06-01

Breast cancer is a common cancer with a leading cause of cancer mortality in women. Currently, the chemotherapy for breast cancer is underdeveloped. Here, we report a novel taspine derivative, HMQ1611, which has anticancer effects using in vitro and in vivo breast cancer models. HMQ1611 reduced cancer cell proliferation in four human breast cancer cell lines including MDA-MB-231, SK-BR-3, ZR-75-30, and MCF-7. HMQ1611 more potently reduced growth of estrogen receptor α (ERα)-positive breast cancer cells (ZR-75-30 and MCF-7) than ERα-negative cells (MDA-MB-231 and SK-BR-3). Moreover, HMQ1611 arrested breast cancer cell cycle at S-phase. In vivo tumor xenograft model, treatment of HMQ1611 significantly reduced tumor size and weight compared with vehicles. We also found that HMQ1611 reduced ERα expression and inhibited membrane ERα-mediated mitogen-activated protein kinase (MAPK) signaling following the stimulation of cells with estrogen. Knockdown of ERα by siRNA transfection in ZR-75-30 cells attenuated HMQ1611 effects. In contrast, overexpression of ERα in MDA-MB-231 cells enhanced HMQ1611 effects, suggesting that ERα pathway mediated HMQ1611's inhibition of breast cancer cell growth in ERα-positive breast cancer. HMQ1611 also reduced phosphorylation of EGF receptor (EGFR) and its downstream signaling players extracellular signal-regulated kinase (ERK)1/2 and AKT activation both in ZR-75-30 and MDA-MB-231 cells. These results showed that the novel compound HMQ1611 had anticancer effects, and partially via ERα and/or EGFR signaling pathways, suggesting that HMQ1611 may be a potential novel candidate for human breast cancer intervention. ©2012 AACR.

Clinical data interoperability based on archetype transformation.

PubMed

Costa, Catalina Martínez; Menárguez-Tortosa, Marcos; Fernández-Breis, Jesualdo Tomás

2011-10-01

The semantic interoperability between health information systems is a major challenge to improve the quality of clinical practice and patient safety. In recent years many projects have faced this problem and provided solutions based on specific standards and technologies in order to satisfy the needs of a particular scenario. Most of such solutions cannot be easily adapted to new scenarios, thus more global solutions are needed. In this work, we have focused on the semantic interoperability of electronic healthcare records standards based on the dual model architecture and we have developed a solution that has been applied to ISO 13606 and openEHR. The technological infrastructure combines reference models, archetypes and ontologies, with the support of Model-driven Engineering techniques. For this purpose, the interoperability infrastructure developed in previous work by our group has been reused and extended to cover the requirements of data transformation. Copyright © 2011 Elsevier Inc. All rights reserved.

Object-oriented model-driven control

NASA Technical Reports Server (NTRS)

Drysdale, A.; Mcroberts, M.; Sager, J.; Wheeler, R.

1994-01-01

A monitoring and control subsystem architecture has been developed that capitalizes on the use of modeldriven monitoring and predictive control, knowledge-based data representation, and artificial reasoning in an operator support mode. We have developed an object-oriented model of a Controlled Ecological Life Support System (CELSS). The model based on the NASA Kennedy Space Center CELSS breadboard data, tracks carbon, hydrogen, and oxygen, carbodioxide, and water. It estimates and tracks resorce-related parameters such as mass, energy, and manpower measurements such as growing area required for balance. We are developing an interface with the breadboard systems that is compatible with artificial reasoning. Initial work is being done on use of expert systems and user interface development. This paper presents an approach to defining universally applicable CELSS monitor and control issues, and implementing appropriate monitor and control capability for a particular instance: the KSC CELSS Breadboard Facility.

Assembly of the novel five-component apicomplexan multi-aminoacyl-tRNA synthetase complex is driven by the hybrid scaffold protein Tg-p43.

PubMed

van Rooyen, Jason M; Murat, Jean-Benjamin; Hammoudi, Pierre-Mehdi; Kieffer-Jaquinod, Sylvie; Coute, Yohann; Sharma, Amit; Pelloux, Hervé; Belrhali, Hassan; Hakimi, Mohamed-Ali

2014-01-01

In Toxoplasma gondii, as in other eukaryotes, a subset of the amino-acyl-tRNA synthetases are arranged into an abundant cytoplasmic multi-aminoacyl-tRNA synthetase (MARS) complex. Through a series of genetic pull-down assays, we have identified the enzymes of this complex as: methionyl-, glutaminyl-, glutamyl-, and tyrosyl-tRNA synthetases, and we show that the N-terminal GST-like domain of a partially disordered hybrid scaffold protein, Tg-p43, is sufficient for assembly of the intact complex. Our gel filtration studies revealed significant heterogeneity in the size and composition of isolated MARS complexes. By targeting the tyrosyl-tRNA synthetases subunit, which was found exclusively in the complete 1 MDa complex, we were able to directly visualize MARS particles in the electron microscope. Image analyses of the negative stain data revealed the observed heterogeneity and instability of these complexes to be driven by the intrinsic flexibility of the domain arrangements within the MARS complex. These studies provide unique insights into the assembly of these ubiquitous but poorly understood eukaryotic complexes.

The Environmental Behavior of Methylene-4,4'-dianiline.

PubMed

Schupp, Thomas; Allmendinger, Hans; Boegi, Christian; Bossuyt, Bart T A; Hidding, Bjoern; Shen, Summer; Tury, Bernard; West, Robert J

2018-06-24

Methylene-4,4'-dianiline (MDA, CAS-No. 101-77-9) is a high production volume intermediate that is mainly processed to diisocyanates and finally polyurethanes. This review summarizes available data concerning the environmental behavior. When released into the environment, MDA distributes into water and subsequently sediment and soil compartments; the air is of little relevance, owed to the low vapor pressure and short atmospheric half-life, which renders MDA non-critical for long-range transport. Biodegradation data present a diverged picture; in some tests, MDA is not readily biodegradable or even not inherent biodegradable; in other tests, MDA turned out to be readily biodegradable (but failing the 10-d window). The history and composition of the inoculum used for testing seem to play an important role, which is underlined by good test results with adapted inoculum. In soil, initially a rapid mineralization is observed, which slows down within the first days due to competitive chemical absorption. The latter results in degradation rates comparable to that of natural organic matter. Under anaerobic conditions, mineralization is poor. Irreversible chemisorption occurs unless soils/sediments are highly reduced. Half-lives due to primary decay do not indicate MDA to be persistent according to the regulatory guidance used in then EU, Canada, or the USA; in Japan, however, due to test results in MITI degradation tests, MDA would be regarded as persistent. The identification of microbial MDA metabolites deserves further research. MDA is not bioaccumulative, but it is toxic to aquatic organisms and mammals. MDA in pore water of soils is rapidly adsorbed on the surface of plant roots. Test runs were too short to draw a final conclusion with regards to transport to stem, leaves, and fruits. Data from structurally similar compounds indicate that such transport would account for less than 1% of the root-adsorbed material.

A comparative study of biodegradability of a carcinogenic aromatic amine (4,4'-diaminodiphenylmethane) with OECD 301 test methods.

PubMed

Mei, Cheng-Fang; Liu, Yan-Zhen; Long, Wei-Nian; Sun, Guo-Ping; Zeng, Guo-Qu; Xu, Mei-Ying; Luan, Tian-Gang

2015-01-01

4,4'-Diaminodiphenylmethane (MDA) is a widely used compound in industries. Studies on the biodegradability of MDA are necessary for environmental hazard identification and risk assessment. Previous studies have suggested that MDA was not readily biodegradable. In the present study, three batches of biodegradation tests (OECD 301A, B, D and F tests) were performed on MDA in June, August and December of 2012. MDA was found to be readily biodegradable and produced colored intermediates in the 301A, B and F test systems. MDA biodegradation measurements were consistent among the three batches of tests. Differences in the extent of biodegradation determined in different methods originated from different test conditions and assessment endpoints. The 301D test has stringent test conditions and is usually performed on chemicals that are toxic to microorganisms, so the test results obtained from 301D tests are less meaningful for evaluating the biodegradability of MDA. The low MDA biodegradation measurements in the 301B tests compared to the 301A and F tests were due to the assessment method, which did not account for MDA incorporation into biomass in its calculation of CO2 formation rate. The differences in the biodegradation rates, as measured by the different OECD 301 test systems, could also be related to the structure and properties of the chemical. For test substances that can be assessed by all OECD 301 test methods, the highest biodegradation values may be obtained from the 301A and F test methods. This study provides new information to assess the environmental fate in the risk assessment of MDA. Copyright © 2014 Elsevier Inc. All rights reserved.

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

PubMed

Williams, Joshua D; Bermudez, Yira; Park, Sophia L; Stratton, Steven P; Uchida, Koji; Hurst, Craig A; Wondrak, Georg T

2014-03-05

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of Six Rounds of Mass Drug Administration on Brugian Filariasis and Soil-Transmitted Helminth Infections in Eastern Indonesia

PubMed Central

Supali, Taniawati; Djuardi, Yenny; Bradley, Mark; Noordin, Rahmah; Rückert, Paul; Fischer, Peter U.

2013-01-01

Background The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). Methodology/Principal Findings We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6th round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5th round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. Conclusions/Significance MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis. PMID:24349595

Impact of six rounds of mass drug administration on Brugian filariasis and soil-transmitted helminth infections in eastern Indonesia.

PubMed

Supali, Taniawati; Djuardi, Yenny; Bradley, Mark; Noordin, Rahmah; Rückert, Paul; Fischer, Peter U

2013-01-01

The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6(th) round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5(th) round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis.

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

PubMed Central

2014-01-01

Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778

Periodic molybdenum disc array for light trapping in amorphous silicon layer

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

Wang, Jiwei; Deng, Changkai; Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210 China

2016-05-15

We demonstrate the light trapping effect in amorphous silicon (a-Si:H) layer by inserting a layer of periodic molybdenum disc array (MDA) between the a-Si:H layer and the quartz substrate, which forms a three-layer structure of Si/MDA/SiO{sub 2}. The MDA layer was fabricated by a new cost-effective method based on nano-imprint technology. Further light absorption enhancement was realized through altering the topography of MDA by annealing it at 700°C. The mechanism of light absorption enhancement in a-Si:H interfaced with MDA was analyzed, and the electric field distribution and light absorption curve of the different layers in the Si/MDA structure under lightmore » illumination of different wavelengths were simulated by employing numerical finite difference time domain (FDTD) solutions.« less

Radiation Response of Cancer Stem-Like Cells From Established Human Cell Lines After Sorting for Surface Markers

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

Al-Assar, Osama; Muschel, Ruth J.; Mantoni, Tine S.

2009-11-15

Purpose: A subpopulation of cancer stem-like cells (CSLC) is hypothesized to exist in different cancer cell lines and to mediate radioresistance in solid tumors. Methods and Materials: Cells were stained for CSLC markers and sorted (fluorescence-activated cell sorter/magnetic beads) to compare foci and radiosensitivity of phosphorylated histone H2AX at Ser 139 (gamma-H2AX) in sorted vs. unsorted populations in eight cell lines from different organs. CSLC properties were examined using anchorage-independent growth and levels of activated Notch1. Validation consisted of testing tumorigenicity and postirradiation enrichment of CSLC in xenograft tumors. Results: The quantity of CSLC was generally in good agreement withmore » primary tumors. CSLC from MDA-MB-231 (breast) and Panc-1 and PSN-1 (both pancreatic) cells had fewer residual gamma-H2AX foci than unsorted cells, pointing to radioresistance of CSLC. However, only MDA-MB-231 CSLC were more radioresistant than unsorted cells. Furthermore, MDA-MB-231 CSLC showed enhanced anchorage-independent growth and overexpression of activated Notch1 protein. The expression of cancer stem cell surface markers in the MDA-MB-231 xenograft model was increased after exposure to fractionated radiation. In contrast to PSN-1 cells, a growth advantage for MDA-MB-231 CSLC xenograft tumors was found compared to tumors arising from unsorted cells. Conclusions: CSLC subpopulations showed no general radioresistant phenotype, despite the quantities of CSLC subpopulations shown to correspond relatively well in other reports. Likewise, CSLC characteristics were found in some but not all of the tested cell lines. The reported problems in testing for CSLC in cell lines may be overcome by additional techniques, beyond sorting for markers.« less

Factors influencing insulin resistance in relation to atherogenicity in mood disorders, the metabolic syndrome and tobacco use disorder.

PubMed

Bortolasci, Chiara Cristina; Vargas, Heber Odebrecht; Vargas Nunes, Sandra Odebrecht; de Melo, Luiz Gustavo Piccoli; de Castro, Márcia Regina Pizzo; Moreira, Estefania Gastaldello; Dodd, Seetal; Barbosa, Décio Sabbatini; Berk, Michael; Maes, Michael

2015-07-01

This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS. Copyright © 2015 Elsevier B.V. All rights reserved.

Withaferin A inhibits experimental epithelial-mesenchymal transition in MCF-10A cells and suppresses vimentin protein level in vivo in breast tumors.

PubMed

Lee, Joomin; Hahm, Eun-Ryeong; Marcus, Adam I; Singh, Shivendra V

2015-06-01

We have shown previously that withaferin A (WA), a bioactive component of the medicinal plant Withania somnifera, inhibits growth of cultured and xenografted human breast cancer cells and prevents breast cancer development and pulmonary metastasis incidence in a transgenic mouse model. The present study was undertaken to determine if the anticancer effect of WA involved inhibition of epithelial-mesenchymal transition (EMT). Experimental EMT induced by exposure of MCF-10A cells to tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β) was partially reversed by treatment with WA but not by its structural analogs withanone or withanolide A. Combined TNF-α and TGF-β treatments conferred partial protection against MCF-10A cell migration inhibition by WA. Inhibition of TNF-α and TGF-β-induced MCF-10A cell migration by WA exposure was modestly attenuated by knockdown of E-cadherin protein. MCF-7 and MDA-MB-231 cells exposed to WA exhibited sustained (MCF-7) or transient (MDA-MB-231) induction of E-cadherin protein. On the other hand, the level of vimentin protein was increased markedly after 24 h treatment of MDA-MB-231 cells with WA. WA-induced apoptosis was not affected by vimentin protein knockdown in MDA-MB-231 cells. Protein level of vimentin was significantly lower in the MDA-MB-231 xenografts as well as in MMTV-neu tumors from WA-treated mice compared with controls. The major conclusions of the present study are that (a) WA treatment inhibits experimental EMT in MCF-10A cells, and (b) mammary cancer growth inhibition by WA administration is associated with suppression of vimentin protein expression in vivo. © 2013 Wiley Periodicals, Inc.

Missing the Mark? A Two Time Point Cohort Study Estimating Intestinal Parasite Prevalence in Informal Settlements in Lima, Peru.

PubMed

Cooper, Michael Townsend; Searing, Rapha A; Thompson, David M; Bard, David; Carabin, Hélène; Gonzales, Carlos; Zavala, Carmen; Woodson, Kyle; Naifeh, Monique

2017-01-01

Objectives: The World Health Organization's (WHO) recommendations list Peru as potentially needing prevention of soil-transmitted helminthiasis (STH). Prevalence of STH varies regionally and remains understudied in the newest informal settlements of the capital city, Lima. The purpose of this study was to evaluate the need for Mass Drug Administration (MDA) of antiparasitic drugs in the newest informal settlements of Lima. The aim of this study was to estimate the season-specific prevalence of STH to determine if these prevalence estimates met the WHO threshold for MDA in 3 informal settlements. Methods : A 2 time point cohort study was conducted among a sample of 140 children aged 1 to 10 years living in 3 purposively sampled informal settlements of Lima, Peru. Children were asked to provide 2 stool samples that were analyzed with the spontaneous sedimentation in tube technique. The season-specific prevalence proportions of MDA-targeted STH were estimated using a hidden (latent) Markov modeling approach to adjust for repeated measurements over the 2 seasons and the imperfect validity of the screening tests. Results : The prevalence of MDA targeted STH was low at 2.2% (95% confidence interval = 0.3% to 6%) and 3.8% (95% confidence interval = 0.7% to 9.3%) among children sampled in the summer and winter months, respectively, when using the most conservative estimate of test sensitivity. These estimates were below the WHO threshold for MDA (20%). Conclusions : Empiric treatment for STH by organizations active in the newest informal settlements is not supported by the data and could contribute to unnecessary medication exposures and poor allocation of resources.

Missing the Mark? A Two Time Point Cohort Study Estimating Intestinal Parasite Prevalence in Informal Settlements in Lima, Peru

PubMed Central

Cooper, Michael Townsend; Searing, Rapha A.; Thompson, David M.; Bard, David; Carabin, Hélène; Gonzales, Carlos; Zavala, Carmen; Woodson, Kyle; Naifeh, Monique

2017-01-01

Objectives: The World Health Organization’s (WHO) recommendations list Peru as potentially needing prevention of soil-transmitted helminthiasis (STH). Prevalence of STH varies regionally and remains understudied in the newest informal settlements of the capital city, Lima. The purpose of this study was to evaluate the need for Mass Drug Administration (MDA) of antiparasitic drugs in the newest informal settlements of Lima. The aim of this study was to estimate the season-specific prevalence of STH to determine if these prevalence estimates met the WHO threshold for MDA in 3 informal settlements. Methods: A 2 time point cohort study was conducted among a sample of 140 children aged 1 to 10 years living in 3 purposively sampled informal settlements of Lima, Peru. Children were asked to provide 2 stool samples that were analyzed with the spontaneous sedimentation in tube technique. The season-specific prevalence proportions of MDA-targeted STH were estimated using a hidden (latent) Markov modeling approach to adjust for repeated measurements over the 2 seasons and the imperfect validity of the screening tests. Results: The prevalence of MDA targeted STH was low at 2.2% (95% confidence interval = 0.3% to 6%) and 3.8% (95% confidence interval = 0.7% to 9.3%) among children sampled in the summer and winter months, respectively, when using the most conservative estimate of test sensitivity. These estimates were below the WHO threshold for MDA (20%). Conclusions: Empiric treatment for STH by organizations active in the newest informal settlements is not supported by the data and could contribute to unnecessary medication exposures and poor allocation of resources. PMID:29152541

Risk Driven Outcome-Based Command and Control (C2) Assessment

DTIC Science & Technology

2000-01-01

shaping the risk ranking scores into more interpretable and statistically sound risk measures. Regression analysis was applied to determine what...Architecture Framework Implementation, AFCEA Coursebook 503J, February 8-11, 2000, San Diego, California. [Morgan and Henrion, 1990] M. Granger Morgan and

Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

PubMed

Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

2015-12-01

Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

PubMed Central

Calvo, A; Catena, R; Noble, MS; Carbott, D; Gil-Bazo, I; Gonzalez-Moreno, O; Huh, J-I; Sharp, R; Qiu, T-H; Anver, MR; Merlino, G; Dickson, RB; Johnson, MD; Green, JE

2009-01-01

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C (TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-α-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P < 0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer. PMID:18504437

Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

PubMed

Khalaf-Allah, Abd El-Rahman M; El-Gengaihi, Souad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

2016-01-01

The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.