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Sample records for multi-robot multi-target particle

  1. Multi-Robot, Multi-Target Particle Swarm Optimization Search in Noisy Wireless Environments

    SciTech Connect

    Kurt Derr; Milos Manic

    2009-05-01

    Multiple small robots (swarms) can work together using Particle Swarm Optimization (PSO) to perform tasks that are difficult or impossible for a single robot to accomplish. The problem considered in this paper is exploration of an unknown environment with the goal of finding a target(s) at an unknown location(s) using multiple small mobile robots. This work demonstrates the use of a distributed PSO algorithm with a novel adaptive RSS weighting factor to guide robots for locating target(s) in high risk environments. The approach was developed and analyzed on multiple robot single and multiple target search. The approach was further enhanced by the multi-robot-multi-target search in noisy environments. The experimental results demonstrated how the availability of radio frequency signal can significantly affect robot search time to reach a target.

  2. A Particle Multi-Target Tracker for Superpositional Measurements Using Labeled Random Finite Sets

    NASA Astrophysics Data System (ADS)

    Papi, Francesco; Kim, Du Yong

    2015-08-01

    In this paper we present a general solution for multi-target tracking with superpositional measurements. Measurements that are functions of the sum of the contributions of the targets present in the surveillance area are called superpositional measurements. We base our modelling on Labeled Random Finite Set (RFS) in order to jointly estimate the number of targets and their trajectories. This modelling leads to a labeled version of Mahler's multi-target Bayes filter. However, a straightforward implementation of this tracker using Sequential Monte Carlo (SMC) methods is not feasible due to the difficulties of sampling in high dimensional spaces. We propose an efficient multi-target sampling strategy based on Superpositional Approximate CPHD (SA-CPHD) filter and the recently introduced Labeled Multi-Bernoulli (LMB) and Vo-Vo densities. The applicability of the proposed approach is verified through simulation in a challenging radar application with closely spaced targets and low signal-to-noise ratio.

  3. Multi-robot control interface

    DOEpatents

    Bruemmer, David J.; Walton, Miles C.

    2011-12-06

    Methods and systems for controlling a plurality of robots through a single user interface include at least one robot display window for each of the plurality of robots with the at least one robot display window illustrating one or more conditions of a respective one of the plurality of robots. The user interface further includes at least one robot control window for each of the plurality of robots with the at least one robot control window configured to receive one or more commands for sending to the respective one of the plurality of robots. The user interface further includes a multi-robot common window comprised of information received from each of the plurality of robots.

  4. INL Multi-Robot Control Interface

    Energy Science and Technology Software Center (ESTSC)

    2005-03-30

    The INL Multi-Robot Control Interface controls many robots through a single user interface. The interface includes a robot display window for each robot showing the robot’s condition. More than one window can be used depending on the number of robots. The user interface also includes a robot control window configured to receive commands for sending to the respective robot and a multi-robot common window showing information received from each robot.

  5. Particle filter for state estimation of jump Markov nonlinear system with application to multi-targets tracking

    NASA Astrophysics Data System (ADS)

    Han, Hua; Ding, Yongsheng; Hao, Kuangrong; Hu, Liangjian

    2013-07-01

    In this article, we first introduce the problem of state estimation of jump Markov nonlinear systems (JMNSs). Since the density evolution method for predictor equations satisfies Fokker-Planck-Kolmogorov equation (FPKE) in Bayes estimation, the FPKE in conjunction with Bayes' conditional density update formula can provide optimal estimation for a general continuous-discrete nonlinear filtering problem. It is well known that the analytical solution of the FPKE and Bayes' formula is extremely difficult to obtain except a few special cases. Hence, we try to design a particle filter to achieve Bayes estimation of the JMNSs. In order to test the viability of our algorithm, we apply it to multiple targets tracking in video surveillance. Before starting simulation, we introduce the 'birth' and 'death' description of targets, targets' transitional probability model, and observation probability. The experiment results show good performance of our proposed filter for multiple targets tracking.

  6. A Framework for Multi Robot Guidance Control

    NASA Astrophysics Data System (ADS)

    Keskin, Onur; Uyar, Erol

    In this paper we present a framework for path planning and path finding for multiple mobile robots with global vision. Our framework model considers the agents’ dynamic status and their environment with obstacles to perform given tasks. The global vision system provides feedback to main controller computer and mobile robots are directed towards to their tasks with avoiding obstacles and without any collision. Different kinds of scenario are prepared to simulate manipulating tasks and non-collision behavior with our framework. Experiment results with Lego Mindstorms NXT shows that our framework can be used where a multi robot system is needed with minimum resources.

  7. Multi-robot operator control unit

    NASA Astrophysics Data System (ADS)

    Powell, D.; Gilbreath, G.; Bruch, M.

    2006-05-01

    Space and Naval Warfare Systems Center, San Diego (SSC San Diego) has developed an unmanned vehicle and sensor operator control interface capable of simultaneously controlling and monitoring multiple sets of heterogeneous systems. The modularity, scalability and flexible user interface of the Multi-robot Operator Control Unit (MOCU) accommodates a wide range of vehicles and sensors in varying mission scenarios. MOCU currently controls all of the SSC San Diego developmental vehicles (land, air, sea, and undersea), including the SPARTAN Advanced Concept Technology Demonstration (ACTD) Unmanned Surface Vehicle (USV), the iRobot PackBot, and the Family of Integrated Rapid Response Equipment (FIRRE) vehicles and sensors. This paper will discuss how software and hardware modularity has allowed SSC San Diego to create a single operator control unit (OCU) with the capability to control a wide variety of unmanned systems.

  8. A modular approach to multi-robot control

    SciTech Connect

    Anderson, R.J.; Lilly, K.W.

    1996-03-01

    The ability to rapidly command multi-robot behavior is crucial for the acceptance and effective utilization of multiple robot control. To achieve this, a modular- multiple robot control solution is being, pursued using the SMART modular control architecture. This paper investigates the development of a new dual-arm kinematics module (DUAL-KLN) which allows multiple robots, previously controlled as separate stand-alone systems, to be controlled as a coordinated multi-robot system. The DUAL-KIN module maps velocity and force information from a center point of interest on a grasped object to the tool centers of each grasping robot. Three-port network equations are used and mapped into the scattering operator domain in a computationally efficient form. Application examples of the DUAL-KLN module in multi-robot coordinated control are given.

  9. Graph rigidity and localization of multi-robot formations.

    PubMed

    Zhang, Fan

    2004-05-01

    This paper provides theoretical foundation for the problem of localization in multi-robot formations. Sufficient and necessary conditions for completely localizing a formation of mobile robots/vehicles in SE(2) based on distributed sensor networks and graph rigidity are proposed. A method for estimating the quality of localizations via a linearized weighted least-squares algorithm is presented, which considers incomplete and noisy sensory information. The approach in this paper had been implemented in a multi-robot system of five car-like robots equipped with omni-directional cameras and IEEE 802.11b wireless network. PMID:15083542

  10. An improved PSO-based approach with dynamic parameter tuning for cooperative multi-robot target searching in complex unknown environments

    NASA Astrophysics Data System (ADS)

    Cai, Yifan; Yang, Simon X.

    2013-10-01

    Target searching in complex unknown environments is a challenging aspect of multi-robot cooperation. In this paper, an improved particle swarm optimisation (PSO) based approach is proposed for a team of mobile robots to cooperatively search for targets in complex unknown environments. The improved cooperation rules for a multi-robot system are applied in the potential field function, which acts as the fitness function of the PSO. The main improvements are the district-difference degree and dynamic parameter tuning. In the simulation studies, various complex situations are investigated and compared to the previous research results. The results demonstrate that the proposed approach can enable the multi-robot system to accomplish the target searching tasks in complex unknown environments.

  11. Cubature Information SMC-PHD for Multi-Target Tracking.

    PubMed

    Liu, Zhe; Wang, Zulin; Xu, Mai

    2016-01-01

    In multi-target tracking, the key problem lies in estimating the number and states of individual targets, in which the challenge is the time-varying multi-target numbers and states. Recently, several multi-target tracking approaches, based on the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter, have been presented to solve such a problem. However, most of these approaches select the transition density as the importance sampling (IS) function, which is inefficient in a nonlinear scenario. To enhance the performance of the conventional SMC-PHD filter, we propose in this paper two approaches using the cubature information filter (CIF) for multi-target tracking. More specifically, we first apply the posterior intensity as the IS function. Then, we propose to utilize the CIF algorithm with a gating method to calculate the IS function, namely CISMC-PHD approach. Meanwhile, a fast implementation of the CISMC-PHD approach is proposed, which clusters the particles into several groups according to the Gaussian mixture components. With the constructed components, the IS function is approximated instead of particles. As a result, the computational complexity of the CISMC-PHD approach can be significantly reduced. The simulation results demonstrate the effectiveness of our approaches. PMID:27171088

  12. Cubature Information SMC-PHD for Multi-Target Tracking

    PubMed Central

    Liu, Zhe; Wang, Zulin; Xu, Mai

    2016-01-01

    In multi-target tracking, the key problem lies in estimating the number and states of individual targets, in which the challenge is the time-varying multi-target numbers and states. Recently, several multi-target tracking approaches, based on the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter, have been presented to solve such a problem. However, most of these approaches select the transition density as the importance sampling (IS) function, which is inefficient in a nonlinear scenario. To enhance the performance of the conventional SMC-PHD filter, we propose in this paper two approaches using the cubature information filter (CIF) for multi-target tracking. More specifically, we first apply the posterior intensity as the IS function. Then, we propose to utilize the CIF algorithm with a gating method to calculate the IS function, namely CISMC-PHD approach. Meanwhile, a fast implementation of the CISMC-PHD approach is proposed, which clusters the particles into several groups according to the Gaussian mixture components. With the constructed components, the IS function is approximated instead of particles. As a result, the computational complexity of the CISMC-PHD approach can be significantly reduced. The simulation results demonstrate the effectiveness of our approaches. PMID:27171088

  13. Multi-robot Task Allocation for Search and Rescue Missions

    NASA Astrophysics Data System (ADS)

    Hussein, Ahmed; Adel, Mohamed; Bakr, Mohamed; Shehata, Omar M.; Khamis, Alaa

    2014-12-01

    Many researchers from academia and industry are attracted to investigate how to design and develop robust versatile multi-robot systems by solving a number of challenging and complex problems such as task allocation, group formation, self-organization and much more. In this study, the problem of multi-robot task allocation (MRTA) is tackled. MRTA is the problem of optimally allocating a set of tasks to a group of robots to optimize the overall system performance while being subjected to a set of constraints. A generic market-based approach is proposed in this paper to solve this problem. The efficacy of the proposed approach is quantitatively evaluated through simulation and real experimentation using heterogeneous Khepera-III mobile robots. The results from both simulation and experimentation indicate the high performance of the proposed algorithms and their applicability in search and rescue missions.

  14. Decentralized multi-robot simultaneous localization and mapping

    NASA Astrophysics Data System (ADS)

    Jaai, R.; Chopra, N.; Balachandran, B.; Karki, H.

    2011-04-01

    In the simultaneous localization and mapping (SLAM) problem, one addresses the problem of using mobile sensor platforms or robotic systems to map unknown environments while simultaneously localizing the mobile systems relative to the map. Applications include mapping in oil storage tanks, oil pipes, search and rescue operations, surveillance operations, exploration operations. In this effort, a previously proposed multi-robot localization algorithm is extended to implement SLAM. The decentralized algorithm is demonstrated to work in dynamic robot networks. Experimental and numerical studies conducted with multiple networked mobile platforms are also discussed to validate the analytical findings.

  15. A Biologically Inspired Cooperative Multi-Robot Control Architecture

    NASA Technical Reports Server (NTRS)

    Howsman, Tom; Craft, Mike; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

    2002-01-01

    A prototype cooperative multi-robot control architecture suitable for the eventual construction of large space structures has been developed. In nature, there are numerous examples of complex architectures constructed by relatively simple insects, such as termites and wasps, which cooperatively assemble their nests. The prototype control architecture emulates this biological model. Actions of each of the autonomous robotic construction agents are only indirectly coordinated, thus mimicking the distributed construction processes of various social insects. The robotic construction agents perform their primary duties stigmergically i.e., without direct inter-agent communication and without a preprogrammed global blueprint of the final design. Communication and coordination between individual agents occurs indirectly through the sensed modifications that each agent makes to the structure. The global stigmergic building algorithm prototyped during the initial research assumes that the robotic builders only perceive the current state of the structure under construction. Simulation studies have established that an idealized form of the proposed architecture was indeed capable of producing representative large space structures with autonomous robots. This paper will explore the construction simulations in order to illustrate the multi-robot control architecture.

  16. A Stigmergic Cooperative Multi-Robot Control Architecture

    NASA Technical Reports Server (NTRS)

    Howsman, Thomas G.; O'Neil, Daniel; Craft, Michael A.

    2004-01-01

    In nature, there are numerous examples of complex architectures constructed by relatively simple insects, such as termites and wasps, which cooperatively assemble their nests. A prototype cooperative multi-robot control architecture which may be suitable for the eventual construction of large space structures has been developed which emulates this biological model. Actions of each of the autonomous robotic construction agents are only indirectly coordinated, thus mimicking the distributed construction processes of various social insects. The robotic construction agents perform their primary duties stigmergically, i.e., without direct inter-agent communication and without a preprogrammed global blueprint of the final design. Communication and coordination between individual agents occurs indirectly through the sensed modifications that each agent makes to the structure. The global stigmergic building algorithm prototyped during the initial research assumes that the robotic builders only perceive the current state of the structure under construction. Simulation studies have established that an idealized form of the proposed architecture was indeed capable of producing representative large space structures with autonomous robots. This paper will explore the construction simulations in order to illustrate the multi-robot control architecture.

  17. Multi-robot team design for real-world applications

    SciTech Connect

    Parker, L.E.

    1996-10-01

    Many of these applications are in dynamic environments requiring capabilities distributed in functionality, space, or time, and therefore often require teams of robots to work together. While much research has been done in recent years, current robotics technology is still far from achieving many of the real world applications. Two primary reasons for this technology gap are that (1) previous work has not adequately addressed the issues of fault tolerance and adaptivity in multi-robot teams, and (2) existing robotics research is often geared at specific applications and is not easily generalized to different, but related, applications. This paper addresses these issues by first describing the design issues of key importance in these real-world cooperative robotics applications: fault tolerance, reliability, adaptivity, and coherence. We then present a general architecture addressing these design issues (called ALLIANCE) that facilities multi-robot cooperation of small- to medium-sized teams in dynamic environments, performing missions composed of loosely coupled subtasks. We illustrate an implementation of ALLIANCE in a real-world application, called Bounding Overwatch, and then discuss how this architecture addresses our key design issues.

  18. Cooperative multi-robot observation of multiple moving targets

    SciTech Connect

    Parker, L.E.; Emmons, B.A.

    1997-03-01

    An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring, or observing, the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications of this type, the use of multiple sensors dynamically moving over time is required. In this paper, the authors investigate the sue of a cooperative team of autonomous sensor-based robots for multi-robot observation of multiple moving targets. They focus primarily on developing the distributed control strategies that allow the robot team to attempt to maximize the collective tie during which each object is being observed by at least one robot in the area of interest. The initial efforts in this problem address the aspects of distributed control in homogeneous robot teams with equivalent sensing and movement capabilities working in an uncluttered, bounded area. This paper first formalizes the problem, discusses related work, and then shows that this problem is NP-hard. They then present a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level control.

  19. Multi Robot Flocking Using Cooperative Control for Space Exploration

    NASA Astrophysics Data System (ADS)

    Chandran, Priya

    2012-07-01

    This paper aims at achieving flocking behavior of multi robot systems for space explorations. Cooperative control of unmanned vehicles is used in the survey of unknown environments. Distributed control of multiple vehicles achieves the objective of exploration of wide areas while avoiding obstacles on their path. Gradient based algorithm is used to obtain necessary attractive/repulsive force to maintain flock. Similar force is used to avoid obstacles, which may be present in the environment. Velocity consensus algorithm helps in maintaining the necessary geometry of the flock. A target agent specifies the group behavior for the flock. Two wheel differential robot model with second order dynamics is considered here. Robot motion is assumed to be on plane terrain.

  20. Multi-robot motion control for cooperative observation

    SciTech Connect

    Parker, L.E.

    1997-06-01

    An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring (or observing) the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications involving limited-range sensors, the use of multiple sensors dynamically moving over time is required. In this paper, the authors investigate the use of a cooperative team of autonomous sensor-based robots for the observation of multiple moving targets. They focus primarily on developing the distributed control strategies that allow the robot team to attempt to minimize the total time in which targets escape observation by some robot team member in the area of interest. This paper first formalizes the problem and discusses related work. The authors then present a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level reasoning control based on the ALLIANCE formalism. They analyze the effectiveness of the approach by comparing it to 3 other feasible algorithms for cooperative control, showing the superiority of the approach for a large class of problems.

  1. A stochastic grid filter for multi-target tracking

    NASA Astrophysics Data System (ADS)

    Kim, Surrey; Kouritzin, Michael A.; Long, Hongwei; McCrosky, Jesse D.; Zhao, Xingqiu

    2004-08-01

    In this paper, we discuss multi-target tracking for a submarine model based on incomplete observations. The submarine model is a weakly interacting stochastic dynamic system with several submarines in the underlying region. Observations are obtained at discrete times from a number of sonobuoys equipped with hydrophones and consist of a nonlinear function of the current locations of submarines corrupted by additive noise. We use filtering methods to find the best estimation for the locations of the submarines. Our signal is a measure-valued process, resulting in filtering equations that can not be readily implemented. We develop Markov chain approximation approach to solve the filtering equation for our model. Our Markov chains are constructed by dividing the multi-target state space into cells, evolving particles in these cells, and employing a random time change approach. These approximations converge to the unnormalized conditional distribution of the signal process based on the back observations. Finally we present some simulation results by using the refining stochastic grid (REST) filter (developed from our Markov chain approximation method).

  2. An intelligent multi-target tracking system

    NASA Astrophysics Data System (ADS)

    Heyerdahl, E.

    1987-07-01

    An implementation of a general tracking system, integrating the target acquisition and tracking subsystems, was developed. It is based on image analysis and extensive use of models. The system permits improvements compared to in-service trackers in the sense that it enables multi-target tracking, automatic acquisition also during tracking and tracking through obscurations. The system is an implementation of a general tracking system. This system produces alternative estimates of a target and projects the corresponding objects into the image plane. To do this estimates of the projecting function are used. The different projections are synthesized through a thresholding process. The implemented system uses parallel Kalman filters to produce the object estimates and estimates the sensor position through a model of sensor dynamics and measurements of sensor angle velocity. Results, produced by the implemented system from IR imagery of a moving target in field are presented.

  3. Task-oriented multi-robot learning in behavior-based systems

    SciTech Connect

    Parker, L.E.

    1996-12-31

    A large application domain for multi-robot teams involves task- oriented missions, in which potentially heterogeneous robots must solve several distinct tasks. Previous research addressing this problem in multi-robot systems has largely focused on issues of efficiency, while ignoring the real-world situated robot needs of fault tolerance` and adaptivity. This paper addresses this problem by developing an architecture called L-ALLIANCE that incorporates task- oriented action selection mechanisms into a behavior-based system, thus increasing the efficiency of robot team performance while maintaining the desirable characteristics of fault tolerance and adaptivity. We present our investigations of several competing control strategies and derive an approach that works well in a wide variety of multi-robot task-oriented mission scenarios. We provide a formal model of this technique to illustrate how it can be incorporated into any behavior-based system.

  4. Motivation and Context-Based Multi-Robot Architecture for Dynamic Task, Role and Behavior Selections

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Hyun; Kim, Jong-Hwan

    This paper proposes a multi-robot coordination architecture for dynamic task, role and behavior selections. The proposed architecture employs the motivation of task, the utility of role, a probabilistic behavior selection and a team strategy for efficient multi-robot coordination. Multiple robots in a team can coordinate with each other by selecting appropriate task, role and behavior in adversarial and dynamic environment. The effectiveness of the proposed architecture is demonstrated in dynamic environment robot soccer by carrying out computer simulation and real environment.

  5. Multi-target compressive laser ranging

    NASA Astrophysics Data System (ADS)

    Pandit, Pushkar P.; Dahl, Jason R.; Barber, Zeb W.; Babbitt, W. Randall

    2014-05-01

    Compressive laser ranging (CLR) is a method that exploits the sparsity available in the range domain using compressive sensing methods to directly obtain range domain information. Conventional ranging methods are marred by requirements of high bandwidth analog detection which includes severe SNR fall off with bandwidth in analog-to-digital conversion (ADC). Compressive laser ranging solves this problem by obtaining sub-centimeter resolution while using low bandwidth detection. High rate digital pulse pattern generators and off the shelf photonic devices are used to modulate the transmitted and received light from a superluminescent diode. CLR detection is demonstrated using low bandwidth, high dynamic range detectors along with photon counting techniques. The use of an incoherent source eliminates speckle issues and enables simplified CLR methods to get multi-target range profiles with 1-3cm resolution. Using compressive sensing methods CLR allows direct range measurements in the sub-Nyquist regime while reducing system resources, in particular the need for high bandwidth ADC.

  6. Multi-robot terrain coverage and task allocation for autonomous detection of landmines

    NASA Astrophysics Data System (ADS)

    Dasgupta, Prithviraj; Muñoz-Meléndez, Angélica; Guruprasad, K. R.

    2012-06-01

    Multi-robot systems comprising of heterogeneous autonomous vehicles on land, air, water are being increasingly used to assist or replace humans in different hazardous missions. Two crucial aspects in such multi-robot systems are to: a) explore an initially unknown region of interest to discover tasks, and, b) allocate and share the discovered tasks between the robots in a coordinated manner using a multi-robot task allocation (MRTA) algorithm. In this paper, we describe results from our research on multi-robot terrain coverage and MRTA algorithms within an autonomous landmine detection scenario, done as part of the COMRADES project. Each robot is equipped with a different type of landmine detection sensor and different sensors, even of the same type, can have different degrees of accuracy. The landmine detection-related operations performed by each robot are abstracted as tasks and multiple robots are required to complete a single task. First, we describe a distributed and robust terrain coverage algorithm that employs Voronoi partitions to divide the area of interest among the robots and then uses a single-robot coverage algorithm to explore each partition for potential landmines. Then, we describe MRTA algorithms that use the location information of discovered potential landmines and employ either a greedy strategy, or, an opportunistic strategy to allocate tasks among the robots while attempting to minimize the time (energy) expended by the robots to perform the tasks. We report experimental results of our algorithms using accurately-simulated Corobot robots within the Webots simulator performing a multi-robot, landmine detection operation.

  7. Behavior-based multi-robot collaboration for autonomous construction tasks

    NASA Technical Reports Server (NTRS)

    Stroupe, Ashley; Huntsberger, Terry; Okon, Avi; Aghazarian, Hrand; Robinson, Matthew

    2005-01-01

    The Robot Construction Crew (RCC) is a heterogeneous multi-robot system for autonomous construction of a structure through assembly of Long components. The two robot team demonstrates component placement into an existing structure in a realistic environment. The task requires component acquisition, cooperative transport, and cooperative precision manipulation. A behavior-based architecture provides adaptability. The RCC approach minimizes computation, power, communication, and sensing for applicability to space-related construction efforts, but the techniques are applicable to terrestrial construction tasks.

  8. Heterogeneous Multi-Robot System for Mapping Environmental Variables of Greenhouses.

    PubMed

    Roldán, Juan Jesús; Garcia-Aunon, Pablo; Garzón, Mario; de León, Jorge; Del Cerro, Jaime; Barrientos, Antonio

    2016-01-01

    The productivity of greenhouses highly depends on the environmental conditions of crops, such as temperature and humidity. The control and monitoring might need large sensor networks, and as a consequence, mobile sensory systems might be a more suitable solution. This paper describes the application of a heterogeneous robot team to monitor environmental variables of greenhouses. The multi-robot system includes both ground and aerial vehicles, looking to provide flexibility and improve performance. The multi-robot sensory system measures the temperature, humidity, luminosity and carbon dioxide concentration in the ground and at different heights. Nevertheless, these measurements can be complemented with other ones (e.g., the concentration of various gases or images of crops) without a considerable effort. Additionally, this work addresses some relevant challenges of multi-robot sensory systems, such as the mission planning and task allocation, the guidance, navigation and control of robots in greenhouses and the coordination among ground and aerial vehicles. This work has an eminently practical approach, and therefore, the system has been extensively tested both in simulations and field experiments. PMID:27376297

  9. Heterogeneous Multi-Robot System for Mapping Environmental Variables of Greenhouses

    PubMed Central

    Roldán, Juan Jesús; Garcia-Aunon, Pablo; Garzón, Mario; de León, Jorge; del Cerro, Jaime; Barrientos, Antonio

    2016-01-01

    The productivity of greenhouses highly depends on the environmental conditions of crops, such as temperature and humidity. The control and monitoring might need large sensor networks, and as a consequence, mobile sensory systems might be a more suitable solution. This paper describes the application of a heterogeneous robot team to monitor environmental variables of greenhouses. The multi-robot system includes both ground and aerial vehicles, looking to provide flexibility and improve performance. The multi-robot sensory system measures the temperature, humidity, luminosity and carbon dioxide concentration in the ground and at different heights. Nevertheless, these measurements can be complemented with other ones (e.g., the concentration of various gases or images of crops) without a considerable effort. Additionally, this work addresses some relevant challenges of multi-robot sensory systems, such as the mission planning and task allocation, the guidance, navigation and control of robots in greenhouses and the coordination among ground and aerial vehicles. This work has an eminently practical approach, and therefore, the system has been extensively tested both in simulations and field experiments. PMID:27376297

  10. Multi-Target State Extraction for the SMC-PHD Filter.

    PubMed

    Si, Weijian; Wang, Liwei; Qu, Zhiyu

    2016-01-01

    The sequential Monte Carlo probability hypothesis density (SMC-PHD) filter has been demonstrated to be a favorable method for multi-target tracking. However, the time-varying target states need to be extracted from the particle approximation of the posterior PHD, which is difficult to implement due to the unknown relations between the large amount of particles and the PHD peaks representing potential target locations. To address this problem, a novel multi-target state extraction algorithm is proposed in this paper. By exploiting the information of measurements and particle likelihoods in the filtering stage, we propose a validation mechanism which aims at selecting effective measurements and particles corresponding to detected targets. Subsequently, the state estimates of the detected and undetected targets are performed separately: the former are obtained from the particle clusters directed by effective measurements, while the latter are obtained from the particles corresponding to undetected targets via clustering method. Simulation results demonstrate that the proposed method yields better estimation accuracy and reliability compared to existing methods. PMID:27322274

  11. Multi-Target State Extraction for the SMC-PHD Filter

    PubMed Central

    Si, Weijian; Wang, Liwei; Qu, Zhiyu

    2016-01-01

    The sequential Monte Carlo probability hypothesis density (SMC-PHD) filter has been demonstrated to be a favorable method for multi-target tracking. However, the time-varying target states need to be extracted from the particle approximation of the posterior PHD, which is difficult to implement due to the unknown relations between the large amount of particles and the PHD peaks representing potential target locations. To address this problem, a novel multi-target state extraction algorithm is proposed in this paper. By exploiting the information of measurements and particle likelihoods in the filtering stage, we propose a validation mechanism which aims at selecting effective measurements and particles corresponding to detected targets. Subsequently, the state estimates of the detected and undetected targets are performed separately: the former are obtained from the particle clusters directed by effective measurements, while the latter are obtained from the particles corresponding to undetected targets via clustering method. Simulation results demonstrate that the proposed method yields better estimation accuracy and reliability compared to existing methods. PMID:27322274

  12. Dynamic, cooperative multi-robot patrolling with a team of UAVs

    NASA Astrophysics Data System (ADS)

    Pippin, Charles E.; Christensen, Henrik; Weiss, Lora

    2013-05-01

    The multi-robot patrolling task has practical relevance in surveillance, search and rescue, and security appli- cations. In this task, a team of robots must repeatedly visit areas in the environment, minimizing the time in-between visits to each. A team of robots can perform this task efficiently; however, challenges remain related to team formation and task assignment. This paper presents an approach for monitoring patrolling performance and dynamically adjusting the task assignment function based on observations of teammate performance. Experimental results are presented from realistic simulations of a cooperative patrolling scenario, using a team of UAVs.

  13. Behavior-Based Multi-Robot Collaboration for Autonomous Construction Tasks

    NASA Technical Reports Server (NTRS)

    Stroupe, Ashley; Huntsberger, Terry; Okon, Avi; Aghazarian, Hrand; Robinson, Matthew

    2005-01-01

    We present a heterogeneous multi-robot system for autonomous construction of a structure through assembly of long components. Placement of a component within an existing structure in a realistic environment is demonstrated on a two-robot team. The task requires component acquisition, cooperative transport, and cooperative precision manipulation. Far adaptability, the system is designed as a behavior-based architecture. Far applicability to space-related construction efforts, computation, power, communication, and sensing are minimized, though the techniques developed are also applicable to terrestrial construction tasks.

  14. Nonlinear robust controller design for multi-robot systems with unknown payloads

    NASA Technical Reports Server (NTRS)

    Song, Y. D.; Anderson, J. N.; Homaifar, A.; Lai, H. Y.

    1992-01-01

    This work is concerned with the control problem of a multi-robot system handling a payload with unknown mass properties. Force constraints at the grasp points are considered. Robust control schemes are proposed that cope with the model uncertainty and achieve asymptotic path tracking. To deal with the force constraints, a strategy for optimally sharing the task is suggested. This strategy basically consists of two steps. The first detects the robots that need help and the second arranges that help. It is shown that the overall system is not only robust to uncertain payload parameters, but also satisfies the force constraints.

  15. A reinforcement learning trained fuzzy neural network controller for maintaining wireless communication connections in multi-robot systems

    NASA Astrophysics Data System (ADS)

    Zhong, Xu; Zhou, Yu

    2014-05-01

    This paper presents a decentralized multi-robot motion control strategy to facilitate a multi-robot system, comprised of collaborative mobile robots coordinated through wireless communications, to form and maintain desired wireless communication coverage in a realistic environment with unstable wireless signaling condition. A fuzzy neural network controller is proposed for each robot to maintain the wireless link quality with its neighbors. The controller is trained through reinforcement learning to establish the relationship between the wireless link quality and robot motion decision, via consecutive interactions between the controller and environment. The tuned fuzzy neural network controller is applied to a multi-robot deployment process to form and maintain desired wireless communication coverage. The effectiveness of the proposed control scheme is verified through simulations under different wireless signal propagation conditions.

  16. Towards Human-Friendly Efficient Control of Multi-Robot Teams

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Theodoridis, Theodoros; Barrero, David F.; Hu, Huosheng; McDonald-Maiers, Klaus

    2013-01-01

    This paper explores means to increase efficiency in performing tasks with multi-robot teams, in the context of natural Human-Multi-Robot Interfaces (HMRI) for command and control. The motivating scenario is an emergency evacuation by a transport convoy of unmanned ground vehicles (UGVs) that have to traverse, in shortest time, an unknown terrain. In the experiments the operator commands, in minimal time, a group of rovers through a maze. The efficiency of performing such tasks depends on both, the levels of robots' autonomy, and the ability of the operator to command and control the team. The paper extends the classic framework of levels of autonomy (LOA), to levels/hierarchy of autonomy characteristic of Groups (G-LOA), and uses it to determine new strategies for control. An UGVoriented command language (UGVL) is defined, and a mapping is performed from the human-friendly gesture-based HMRI into the UGVL. The UGVL is used to control a team of 3 robots, exploring the efficiency of different G-LOA; specifically, by (a) controlling each robot individually through the maze, (b) controlling a leader and cloning its controls to followers, and (c) controlling the entire group. Not surprisingly, commands at increased G-LOA lead to a faster traverse, yet a number of aspects are worth discussing in this context.

  17. Multi-robot task allocation based on two dimensional artificial fish swarm algorithm

    NASA Astrophysics Data System (ADS)

    Zheng, Taixiong; Li, Xueqin; Yang, Liangyi

    2007-12-01

    The problem of task allocation for multiple robots is to allocate more relative-tasks to less relative-robots so as to minimize the processing time of these tasks. In order to get optimal multi-robot task allocation scheme, a twodimensional artificial swarm algorithm based approach is proposed in this paper. In this approach, the normal artificial fish is extended to be two dimension artificial fish. In the two dimension artificial fish, each vector of primary artificial fish is extended to be an m-dimensional vector. Thus, each vector can express a group of tasks. By redefining the distance between artificial fish and the center of artificial fish, the behavior of two dimension fish is designed and the task allocation algorithm based on two dimension artificial swarm algorithm is put forward. At last, the proposed algorithm is applied to the problem of multi-robot task allocation and comparer with GA and SA based algorithm is done. Simulation and compare result shows the proposed algorithm is effective.

  18. Sequential measurement-driven multi-target Bayesian filter

    NASA Astrophysics Data System (ADS)

    Liu, Zong-xiang; Li, Li-juan; Xie, Wei-xin; Li, Liang-qun

    2015-12-01

    Bayesian filter is an efficient approach for multi-target tracking in the presence of clutter. Recently, considerable attention has been focused on probability hypothesis density (PHD) filter, which is an intensity approximation of the multi-target Bayesian filter. However, PHD filter is inapplicable to cases in which target detection probability is low. The use of this filter may result in a delay in data processing because it handles received measurements periodically, once every sampling period. To track multiple targets in the case of low detection probability and to handle received measurements in real time, we propose a sequential measurement-driven Bayesian filter. The proposed filter jointly propagates the marginal distributions and existence probabilities of each target in the filter recursion. We also present an implementation of the proposed filter for linear Gaussian models. Simulation results demonstrate that the proposed filter can more accurately track multiple targets than the Gaussian mixture PHD filter or cardinalized PHD filter.

  19. A Case Study of Collaboration with Multi-Robots and Its Effect on Children's Interaction

    ERIC Educational Resources Information Center

    Hwang, Wu-Yuin; Wu, Sheng-Yi

    2014-01-01

    Learning how to carry out collaborative tasks is critical to the development of a student's capacity for social interaction. In this study, a multi-robot system was designed for students. In three different scenarios, students controlled robots in order to move dice; we then examined their collaborative strategies and their behavioral…

  20. Cooperative motion control for multi-target observation

    SciTech Connect

    Parker, L.E.

    1997-08-01

    An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring (or observing) the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications involving limited-range sensors, the use of multiple sensors dynamically moving over time is required. In this paper, the author investigates the use of a cooperative team of autonomous sensor-based robots for the observation of multiple moving targets. The focus is primarily on developing the distributed control strategies that allow the robot team to attempt to minimize the total time in which targets escape observation by some robot team member in the area of interest. This paper first formalizes the problem and discusses related work. The author then presents a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level reasoning control based on the ALLIANCE formalism. The effectiveness of the approach is analyzed by comparing it to three other feasible algorithms for cooperative control, showing the superiority of the approach for a large class of problems.

  1. L-ALLIANCE: a mechanism for adaptive action selection in heterogeneous multi-robot teams

    SciTech Connect

    Parker, L.E.

    1995-11-01

    In practical applications of robotics, it is usually quite difficult, if not impossible, for the system designer to fully predict the environmental states in which the robots will operate. The complexity of the problem is further increased when dealing with teams of robots which themselves may be incompletely known and characterized in advance. It is thus highly desirable for robot teams to be able to adapt their performance during the mission due to changes in the environment, or to changes in other robot team members. In previous work, we introduced a behavior-based mechanism called the ALLIANCE architecture -- that facilitates the fault tolerant cooperative control of multi-robot teams. However, this previous work did not address the issue of how to dynamically update the control parameters during a mission to adapt to ongoing changes in the environment or in the robot team, and to ensure the efficiency of the collective team actions. In this paper, we address this issue by proposing the L-ALLIANCE mechanism, which defines an automated method whereby robots can use knowledge learned from previous experience to continually improve their collective action selection when working on missions composed of loosely coupled, discrete subtasks. This ability to dynamically update robotic control parameters provides a number of distinct advantages: it alleviates the need for human tuning of control parameters, it facilitates the use of custom-designed multi-robot teams for any given application, it improves the efficiency of the mission performance, and It allows robots to continually adapt their performance over time due to changes in the robot team and/or the environment. We describe the L-ALLIANCE mechanism, present the results of various alternative update strategies we investigated, present the formal model of the L-ALLIANCE mechanism, and present the results of a simple proof of concept implementation on a small team of heterogeneous mobile robots.

  2. Dynamical Behavior of Multi-Robot Systems Using Lattice Gas Automata

    SciTech Connect

    Cameron, S.M.; Robinett, R.; Stantz, K.M.; Trahan, M.W.; Wagner, J.S.

    1999-03-11

    Recent attention has been given to the deployment of an adaptable sensor array realized by multi-robotic systems. Our group has been studying the collective behavior of autonomous, multi-agent systems and their applications in the area of remote-sensing and emerging threats. To accomplish such tasks, an interdisciplinary research effort at Sandia National Laboratories are conducting tests in the fields of sensor technology, robotics, and multi-robotic and multi-agents architectures. Our goal is to coordinate a constellation of point sensors that optimizes spatial coverage and multivariate signal analysis using unmanned robotic vehicles (e.g., RATLERs, Robotic All-ten-sin Lunar Exploration Rover-class vehicles). Overall design methodology is to evolve complex collective behaviors realized through simple interaction (kinetic) physics and artificial intelligence to enable real-time operational responses to emerging threats. This paper focuses on our recent work understanding the dynamics of many-body systems using the physics-based hydrodynamic model of lattice gas automata. Three design features are investigated. One, for single-speed robots, a hexagonal nearest-neighbor interaction topology is necessary to preserve standard hydrodynamic flow. Two, adaptability, defined by the swarm's deformation rate, can be controlled through the hydrodynamic viscosity term, which, in turn, is defined by the local robotic interaction rules. Three, due to the inherent non-linearity of the dynamical equations describing large ensembles, development of stability criteria ensuring convergence to equilibrium states is developed by scaling information flow rates relative to a swarm's hydrodynamic flow rate. An initial test case simulates a swarm of twenty-five robots that maneuvers past an obstacle while following a moving target. A genetic algorithm optimizes applied nearest-neighbor forces in each of five spatial regions distributed over the simulation domain. Armed with knowledge, the

  3. Multi-Target Stool DNA Test: Is the Future Here?

    PubMed

    Sweetser, Seth; Ahlquist, David A

    2016-06-01

    Colorectal cancer (CRC) screening reduces CRC incidence and mortality and is widely recommended. However, despite these demonstrated benefits, a large percentage of the population remains unscreened. The multi-target stool DNA (MT-sDNA) test is a new, non-invasive option for CRC screening that has a high accuracy rate in detection of colorectal neoplasia and offers great opportunity to enhance screening uptake. This review provides the current state of the art knowledge about the use of MT-sDNA in CRC screening. PMID:27165404

  4. Multi-target screening of biological samples using LC-MS/MS: focus on chromatographic innovations.

    PubMed

    Kohler, Isabelle; Guillarme, Davy

    2014-05-01

    Multi-target screening of biological fluids is a key tool in clinical and forensic toxicology. A complete toxicological analysis encompasses the sample preparation, the chromatographic separation and the detection. The present review briefly covers the new trends in sample preparation and detection and mainly focuses on the chromatographic stage, since a lot of technical improvements have been proposed over the last years. Among them, columns packed with sub-2 μm fully porous particles and sub-3 μm core-shell particles allow for significant improvements of resolution and higher throughput. Even if reversed-phase LC remains the most widely used chromatographic mode for toxicological screening, hydrophilic interaction chromatography and supercritical fluid chromatography appear as promising alternatives for attaining orthogonal selectivity, retention of polar compounds, and enhanced MS sensitivity. PMID:24946925

  5. Antibacterial Drug Leads: DNA and Enzyme Multi-Targeting

    PubMed Central

    Zhu, Wei; Wang, Yang; Li, Kai; Gao, Jian; Huang, Chun-Hsiang; Chen, Chun-Chi; Ko, Tzu-Ping; Zhang, Yonghui; Guo, Rey-Ting; Oldfield, Eric

    2015-01-01

    We report the results of an investigation of the activity of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)2, and using DSC were found to increase the melting transition by up to 24 °C. Several compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50 values of 100–500 nM and we found good correlations (R2 = 0.89, S. aureus; R2 = 0.79, E. coli)) between experimental and predicted cell growth inhibition by using DNA ΔTm and UPPS IC50 experimental results together with 1 computed descriptor. We also solved the structures of three bisamidines binding to DNA as well as three UPPS structures. Overall, the results are of general interest in the context of the development of resistance-resistant antibiotics that involve multi-targeting. PMID:25574764

  6. Mid-course multi-target tracking using continuous representation

    NASA Technical Reports Server (NTRS)

    Zak, Michail; Toomarian, Nikzad

    1991-01-01

    The thrust of this paper is to present a new approach to multi-target tracking for the mid-course stage of the Strategic Defense Initiative (SDI). This approach is based upon a continuum representation of a cluster of flying objects. We assume that the velocities of the flying objects can be embedded into a smooth velocity field. This assumption is based upon the impossibility of encounters in a high density cluster between the flying objects. Therefore, the problem is reduced to an identification of a moving continuum based upon consecutive time frame observations. In contradistinction to the previous approaches, here each target is considered as a center of a small continuous neighborhood subjected to a local-affine transformation, and therefore, the target trajectories do not mix. Obviously, their mixture in plane of sensor view is apparent. The approach is illustrated by an example.

  7. Bayesian multi-target tracking and sequential object recognition

    NASA Astrophysics Data System (ADS)

    Armbruster, Walter

    2008-04-01

    The paper considers the following problem: given a 3D model of a reference target and a sequence of images of a 3D scene, identify the object in the scene most likely to be the reference target and determine its current pose. Finding the best match in each frame independently of previous decisions is not optimal, since past information is ignored. Our solution concept uses a novel Bayesian framework for multi target tracking and object recognition to define and sequentially update the probability that the reference target is any one of the tracked objects. The approach is applied to problems of automatic lock-on and missile guidance using a laser radar seeker. Field trials have resulted in high target hit probabilities despite low resolution imagery and temporarily highly occluded targets.

  8. Multi-Target Detection from Full-Waveform Airborne Laser Scanner Using Phd Filter

    NASA Astrophysics Data System (ADS)

    Fuse, T.; Hiramatsu, D.; Nakanishi, W.

    2016-06-01

    We propose a new technique to detect multiple targets from full-waveform airborne laser scanner. We introduce probability hypothesis density (PHD) filter, a type of Bayesian filtering, by which we can estimate the number of targets and their positions simultaneously. PHD filter overcomes some limitations of conventional Gaussian decomposition method; PHD filter doesn't require a priori knowledge on the number of targets, assumption of parametric form of the intensity distribution. In addition, it can take a similarity between successive irradiations into account by modelling relative positions of the same targets spatially. Firstly we explain PHD filter and particle filter implementation to it. Secondly we formulate the multi-target detection problem on PHD filter by modelling components and parameters within it. At last we conducted the experiment on real data of forest and vegetation, and confirmed its ability and accuracy.

  9. Development and human factors analysis of an augmented reality interface for multi-robot tele-operation and control

    NASA Astrophysics Data System (ADS)

    Lee, Sam; Lucas, Nathan P.; Ellis, R. Darin; Pandya, Abhilash

    2012-06-01

    This paper presents a seamlessly controlled human multi-robot system comprised of ground and aerial robots of semiautonomous nature for source localization tasks. The system combines augmented reality interfaces capabilities with human supervisor's ability to control multiple robots. The role of this human multi-robot interface is to allow an operator to control groups of heterogeneous robots in real time in a collaborative manner. It used advanced path planning algorithms to ensure obstacles are avoided and that the operators are free for higher-level tasks. Each robot knows the environment and obstacles and can automatically generate a collision-free path to any user-selected target. It displayed sensor information from each individual robot directly on the robot in the video view. In addition, a sensor data fused AR view is displayed which helped the users pin point source information or help the operator with the goals of the mission. The paper studies a preliminary Human Factors evaluation of this system in which several interface conditions are tested for source detection tasks. Results show that the novel Augmented Reality multi-robot control (Point-and-Go and Path Planning) reduced mission completion times compared to the traditional joystick control for target detection missions. Usability tests and operator workload analysis are also investigated.

  10. Performance impact of mutation operators of a subpopulation-based genetic algorithm for multi-robot task allocation problems.

    PubMed

    Liu, Chun; Kroll, Andreas

    2016-01-01

    Multi-robot task allocation determines the task sequence and distribution for a group of robots in multi-robot systems, which is one of constrained combinatorial optimization problems and more complex in case of cooperative tasks because they introduce additional spatial and temporal constraints. To solve multi-robot task allocation problems with cooperative tasks efficiently, a subpopulation-based genetic algorithm, a crossover-free genetic algorithm employing mutation operators and elitism selection in each subpopulation, is developed in this paper. Moreover, the impact of mutation operators (swap, insertion, inversion, displacement, and their various combinations) is analyzed when solving several industrial plant inspection problems. The experimental results show that: (1) the proposed genetic algorithm can obtain better solutions than the tested binary tournament genetic algorithm with partially mapped crossover; (2) inversion mutation performs better than other tested mutation operators when solving problems without cooperative tasks, and the swap-inversion combination performs better than other tested mutation operators/combinations when solving problems with cooperative tasks. As it is difficult to produce all desired effects with a single mutation operator, using multiple mutation operators (including both inversion and swap) is suggested when solving similar combinatorial optimization problems. PMID:27588254

  11. Volumetric compensation of accuracy errors in a multi-robot surgical platform.

    PubMed

    Vicentini, Federico; Magnoni, Paolo; Giussani, Matteo; Tosatti, Lorenzo Molinari

    2015-08-01

    A multi-robot platform, made of a hybrid parallel kinematic machine and 2 KUKA LWR arms, is dedicated to open skull neuro-surgical tasks. Sub-millimeter accuracy is clearly required for both the absolute tool tracking and for good performances in motion compensation when the head is set free to move. An analysis of the sources of inaccuracies, mostly derived from the calibration phase, illustrates that errors are insufficiently reduced by stand-alone calibrations of the single robots. A method for volumetric compensation of errors is reported. A compensation transform is, in fact, computed during an offline training phase for a set of discretized subregions of the constrained head workspace. At runtime, a compensation motion is applied to robots so as to reach the desired real targets on anatomical parts. The resulting end-to-end static accuracy is distributed with median 0.75 mm and below 1 mm for the 95% of tests, with a 1:36 reduction factor from the starting conditions. The accuracy is evaluated also in dynamic tests with mild oscillatory patterns. PMID:26737394

  12. Adapting an ant colony metaphor for multi-robot chemical plume tracing.

    PubMed

    Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

    2012-01-01

    We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments. PMID:22666056

  13. Adapting an Ant Colony Metaphor for Multi-Robot Chemical Plume Tracing

    PubMed Central

    Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

    2012-01-01

    We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments. PMID:22666056

  14. Phenolic thio- and selenosemicarbazones as multi-target drugs.

    PubMed

    Calcatierra, Verónica; López, Óscar; Fernández-Bolaños, José G; Plata, Gabriela B; Padrón, José M

    2015-04-13

    A series of isosteric phenolic thio- and selenosemicarbazones have been obtained by condensation of naturally-occurring phenolic aldehydes and thio(seleno)semicarbazides. Title compounds were designed as potential multi-target drugs, and a series of structure-activity relationships could be established upon their in vitro assays: antioxidant activity, α-glucosidase inhibition and antiproliferative activity against six human tumor cell lines: A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). For the antiradical activity, selenium atom and 2 or 3 phenolic hydroxyl groups proved to be essential motifs; remarkably, the compound with the most potent activity, with a trihydroxyphenyl scaffold (EC50 = 4.87 ± 1.57 μM) was found to be stronger than natural hydroxytyrosol, a potent antioxidant present in olive oil (EC50 = 13.80 ± 1.41 μM). Furthermore, one of the thiosemicarbazones was found to be a strong non-competitive inhibitor of α-glucosidase (Ki = 9.6 ± 1.6 μM), with an 8-fold increase in activity compared to acarbose (Ki = 77.9 ± 11.4 μM), marketed for the treatment of type-2 diabetes. Most of the synthesized compounds also exhibited relevant antiproliferative activities; in particular, seleno derivatives showed GI50 values lower than 6.0 μM for all the tested cell lines; N-naphthyl mono- and dihydroxylated derivatives behaved as more potent antiproliferative agents than 5-fluorouracil or cisplatin. PMID:25752525

  15. Pharmaceutical prerequisites for a multi-target therapy.

    PubMed

    Kroll, U; Cordes, C

    2006-01-01

    The quality of a phytomedicine is defined by the quality of the herbal drug, the manufacturing of the drug preparations and the properties of the finished product, taking into account the special requirements of the individual herbal species in accordance with Good Manufacturing Practice (GMP) standards [2003. Medicinal Products for Human and Veterinary Use. Eudralex, vol. 4 (2003/94/EC)]. The quality control of the complete process is based on pharmacognostic methods, characteristic fingerprint chromatograms, defined amounts of marker substances, physicochemical characteristics and microbiological monitoring. For a herbal multi-component preparation used in multi-target therapy, these pharmaceutical prerequisites have to be ensured for all components and for their combination, as is exemplified by Iberogast((R)) (STW 5) a fixed combination of hydroethanolic extracts of bitter candytuft (Iberis amara), angelica root (Angelicae radix), milk thistle fruit (Silybi mariani fructus), celandine herb (Chelidonii herba), caraway fruit (Carvi fructus), liquorice root (Liquiritiae radix), peppermint herb (Menthae piperitae folium), balm leaf (Melissae folium) and chamomile flower (Matricariae flos) using in the therapy of gastrointestinal complaints (Rösch et al., 2006). The prerequisites for the quality of each of its components according to actual standards are at first the cultivation of the plant material according to the Guidelines for Good Agricultural Practice (GAP) conditions of Medicinal and Aromatic Plants [1998. Z. Arzn. Gew. Pfl. 3, 166-178] to yield a defined raw material of high quality. Characteristic compounds of the extracts had to be identified and different analytical methods such as HPLC, with low coefficients of variation had to be developed to analyze each of the standardized ethanolic extracts and the finished product. At the example of the extract of I. amara these necessary investigations are described. The variability of the plant material in its

  16. A Multi-Robot Sense-Act Approach to Lead to a Proper Acting in Environmental Incidents.

    PubMed

    Conesa-Muñoz, Jesús; Valente, João; Del Cerro, Jaime; Barrientos, Antonio; Ribeiro, Angela

    2016-01-01

    Many environmental incidents affect large areas, often in rough terrain constrained by natural obstacles, which makes intervention difficult. New technologies, such as unmanned aerial vehicles, may help address this issue due to their suitability to reach and easily cover large areas. Thus, unmanned aerial vehicles may be used to inspect the terrain and make a first assessment of the affected areas; however, nowadays they do not have the capability to act. On the other hand, ground vehicles rely on enough power to perform the intervention but exhibit more mobility constraints. This paper proposes a multi-robot sense-act system, composed of aerial and ground vehicles. This combination allows performing autonomous tasks in large outdoor areas by integrating both types of platforms in a fully automated manner. Aerial units are used to easily obtain relevant data from the environment and ground units use this information to carry out interventions more efficiently. This paper describes the platforms and sensors required by this multi-robot sense-act system as well as proposes a software system to automatically handle the workflow for any generic environmental task. The proposed system has proved to be suitable to reduce the amount of herbicide applied in agricultural treatments. Although herbicides are very polluting, they are massively deployed on complete agricultural fields to remove weeds. Nevertheless, the amount of herbicide required for treatment is radically reduced when it is accurately applied on patches by the proposed multi-robot system. Thus, the aerial units were employed to scout the crop and build an accurate weed distribution map which was subsequently used to plan the task of the ground units. The whole workflow was executed in a fully autonomous way, without human intervention except when required by Spanish law due to safety reasons. PMID:27517934

  17. Multi-target siRNA: Therapeutic Strategy for Hepatocellular Carcinoma

    PubMed Central

    Li, Tiejun; Xue, Yuwen; Wang, Guilan; Gu, Tingting; Li, Yunlong; Zhu, York Yuanyuan; Chen, Li

    2016-01-01

    Multiple targets RNAi strategy is a preferred way to treat multigenic diseases, especially cancers. In the study, multi-target siRNAs were designed to inhibit NET-1, EMS1 and VEGF genes in hepatocellular carcinoma (HCC) cells. And multi-target siRNAs showed better silencing effects on NET-1, EMS1 and VEGF, compared with single target siRNA. Moreover, multi-target siRNA showed greater suppression effects on proliferation, migration, invasion, angiogenesis and induced apoptosis in HCC cells. The results suggested that multi-target siRNA might be a preferred strategy for cancer therapy and NET-1, EMS1 and VEGF could be effective targets for HCC treatments. PMID:27390607

  18. Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization

    PubMed Central

    Guan, Yan-Qing; Zheng, Zhe; Huang, Zheng; Li, Zhibin; Niu, Shuiqin; Liu, Jun-Ming

    2014-01-01

    Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-α, and interferon-γ onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance. PMID:24845203

  19. Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization

    NASA Astrophysics Data System (ADS)

    Guan, Yan-Qing; Zheng, Zhe; Huang, Zheng; Li, Zhibin; Niu, Shuiqin; Liu, Jun-Ming

    2014-05-01

    Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-α, and interferon-γ onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance.

  20. Enhanced bandwidth of a microstrip antenna using a parasitic mushroom-like metamaterial structure for multi-robot cooperative navigation

    NASA Astrophysics Data System (ADS)

    Lee, Cherl-Hee; Lee, Jonghun; Kim, Yoon-Gu; An, Jinung

    2015-01-01

    The broadband design of a microstrip patch antenna is presented and experimentally studied for multi-robot cooperation. A parasitic mushroom-like metamaterial (MTM) patch close to a microstrip top patch is excited through gap-coupling, thereby producing a resonance frequency. Because of the design, the resonance frequency of the parasitic MTM patch is adjacent to that of the main patch, and the presented antenna can achieve an enhanced bandwidth of 450 MHz, which is about two times the bandwidth of a conventional patch antenna without the MTM parasitic patch. The error rate of packet transmissions for measuring the distance between a leader robot and a follower robot was also improved by almost two-fold.

  1. A collision avoidance algorithm for the mobile robot and the robot manipulator in multi-robot system

    NASA Astrophysics Data System (ADS)

    Jih, Yeung-Jaw Joe

    1991-08-01

    As the modern, highly automated factory becomes more and more complicated, the collision avoidance between robots and other obstacles in the work space becomes increasingly important as well. A local collision avoidance algorithm which was developed based on the general structure of the Artificial Potential Field Force along with the Strategy Force and the Pseudo Distance Function is presented. In this algorithm, a goal attracting force is defined in order to drive the robot from the starting position to the goal position. When the distance between a robot and obstacle becomes smaller than a pre-defined effective avoidance distance, an artificial repulsion force is generated as a function of the distance resulting in repulsion between the two closing objects. The commanding force (by combining goal attracting force and the repulsion force) drives the robot toward the goal position without colliding with other objects in the work space. Since the repulsion force, developed here, depends on the distance only, the complicated geometric function for the object model is less important in the algorithm used in this dissertation. The simplicity of this improved artificial force collision algorithm would make it possible to be used on a real-time basis within a time variant environment. Further improvement is realized by introducing a Strategy Force within the Artificial Force whenever a locking situation is detected. The Euclidean distance between the objects normally used in this algorithm is also replaced by a defined Pseudo Distance calculated by a Pseudo Distance Function. The Pseudo Distance Function uses basic geometric information between two objects to calculate the Pseudo Distance. The Pseudo Distance is always smaller than the true minimum distance. This greatly simplified robot collision avoidance algorithm is applicable not only on a two-dimensional mobile robot system but on a three-dimensional multi-robot system as well. Simulations are performed on both

  2. Novel multi-targeted polymerase chain reaction for diagnosis of presumed tubercular uveitis

    PubMed Central

    2013-01-01

    Background The objective of this study was to report the use of multi-targeted polymerase chain reaction (PCR) in the diagnosis of presumed tubercular uveitis. Multi-targeted PCR using three targets specific for Mycobacterium tuberculosis, i.e., IS6110, MPB64, and protein b, was performed on intraocular fluid samples of 25 subjects. Nine had presumed tubercular uveitis, six had intraocular inflammation secondary to a nontubercular etiology (disease controls), and ten had no evidence of intraocular inflammation (normal controls). As described previously, response to antitubercular therapy was considered as the gold standard. Results Multi-targeted PCR was positive in seven out of nine patients with presumed tubercular uveitis and negative in all normal and disease controls. The sensitivity and specificity were 77.77% and 100%, respectively. For the diagnosis of presumed tubercular uveitis, multi-targeted PCR had a positive predictive value of 100% and a negative predictive value of 88.88%. Conclusion Multi-targeted PCR can be a valuable tool for diagnosing presumed tubercular uveitis. PMID:23514226

  3. Piezo-microfluidic transport system for multi-targets biochip detections

    NASA Astrophysics Data System (ADS)

    Li, Chia-Chin; Wang, Pei-Wen; Lee, Chih-Kung

    2016-03-01

    Detecting minute trace of interferon-gamma and various bio-markers by using a single biochip was adopted as a platform to examine the technology advancements presented. As bio-detection faces the restriction that only very small quantity of specimen is available, ways to make the best use of the sample available are a must. Since samples concentration will affect the binding rate of an immunoassay, the testing order will become an influencing factor if multiple biomarkers testing situation are needed by using only a single trace of sample. More specifically, if we test disease A first and then detect disease B using the sample just been measured by testing disease A, we most likely will get different results if we reverse the testing order. With an attempt to examine and maybe resolve the issues mentioned above, a micro-fluid control system was developed. The design requirements not only ask for microfluidic control but also demand the system developed has the potential to be integrated within the biochip once its performance is verified. A piezo-vibrating system that can generate traveling waves for microfluidic control was chosen due to its versatility and large force to volume ratio. A simulation software COMSOL was adopted first to predict the microfluidic behavior of the two-mode excited piezo-microfluidic transport system. Secondly, fluorescent particles was used to analyze the microfluidic behavior of system fabricated based on the simulation. Finally, Electrochemistry Impedance Spectroscopy (EIS) was implemented to verify the performance and extendibility of this newly developed system for multi-target detections.

  4. Multi-Target Tracking Based on Multi-Bernoulli Filter with Amplitude for Unknown Clutter Rate

    PubMed Central

    Yuan, Changshun; Wang, Jun; Lei, Peng; Bi, Yanxian; Sun, Zhongsheng

    2015-01-01

    Knowledge of the clutter rate is of critical importance in multi-target Bayesian tracking. However, estimating the clutter rate is a difficult problem in practice. In this paper, an improved multi-Bernoulli filter based on random finite sets for multi-target Bayesian tracking accommodating non-linear dynamic and measurement models, as well as unknown clutter rate, is proposed for radar sensors. The proposed filter incorporates the amplitude information into the state and measurement spaces to improve discrimination between actual targets and clutters, while adaptively generating the new-born object random finite sets using the measurements to eliminate reliance on prior random finite sets. A sequential Monte-Carlo implementation of the proposed filter is presented, and simulations are used to demonstrate the proposed filter’s improvements in estimation accuracy of the target number and corresponding multi-target states, as well as the clutter rate. PMID:26690148

  5. Random finite set multi-target trackers: stochastic geometry for space situational awareness

    NASA Astrophysics Data System (ADS)

    Vo, Ba-Ngu; Vo, Ba-Tuong

    2015-05-01

    This paper describes the recent development in the random finite set RFS paradigm in multi-target tracking. Over the last decade the Probability Hypothesis Density filter has become synonymous with the RFS approach. As result the PHD filter is often wrongly used as a performance benchmark for the RFS approach. Since there is a suite of RFS-based multi-target tracking algorithms, benchmarking tracking performance of the RFS approach by using the PHD filter, the cheapest of these, is misleading. Such benchmarking should be performed with more sophisticated RFS algorithms. In this paper we outline the high-performance RFS-based multi-target trackers such that the Generalized Labled Multi-Bernoulli filter, and a number of efficient approximations and discuss extensions and applications of these filters. Applications to space situational awareness are discussed.

  6. Multi-Target Tracking Based on Multi-Bernoulli Filter with Amplitude for Unknown Clutter Rate.

    PubMed

    Yuan, Changshun; Wang, Jun; Lei, Peng; Bi, Yanxian; Sun, Zhongsheng

    2015-01-01

    Knowledge of the clutter rate is of critical importance in multi-target Bayesian tracking. However, estimating the clutter rate is a difficult problem in practice. In this paper, an improved multi-Bernoulli filter based on random finite sets for multi-target Bayesian tracking accommodating non-linear dynamic and measurement models, as well as unknown clutter rate, is proposed for radar sensors. The proposed filter incorporates the amplitude information into the state and measurement spaces to improve discrimination between actual targets and clutters, while adaptively generating the new-born object random finite sets using the measurements to eliminate reliance on prior random finite sets. A sequential Monte-Carlo implementation of the proposed filter is presented, and simulations are used to demonstrate the proposed filter's improvements in estimation accuracy of the target number and corresponding multi-target states, as well as the clutter rate. PMID:26690148

  7. Distributed Multi-Target Tracking and Data Association in Vision Networks.

    PubMed

    Kamal, Ahmed T; Bappy, Jawadul H; Farrell, Jay A; Roy-Chowdhury, Amit K

    2016-07-01

    Distributed algorithms have recently gained immense popularity. With regards to computer vision applications, distributed multi-target tracking in a camera network is a fundamental problem. The goal is for all cameras to have accurate state estimates for all targets. Distributed estimation algorithms work by exchanging information between sensors that are communication neighbors. Vision-based distributed multi-target state estimation has at least two characteristics that distinguishes it from other applications. First, cameras are directional sensors and often neighboring sensors may not be sensing the same targets, i.e., they are naive with respect to that target. Second, in the presence of clutter and multiple targets, each camera must solve a data association problem. This paper presents an information-weighted, consensus-based, distributed multi-target tracking algorithm referred to as the Multi-target Information Consensus (MTIC) algorithm that is designed to address both the naivety and the data association problems. It converges to the centralized minimum mean square error estimate. The proposed MTIC algorithm and its extensions to non-linear camera models, termed as the Extended MTIC (EMTIC), are robust to false measurements and limited resources like power, bandwidth and the real-time operational requirements. Simulation and experimental analysis are provided to support the theoretical results. PMID:26441444

  8. Cardinality Balanced Multi-Target Multi-Bernoulli Filter with Error Compensation.

    PubMed

    He, Xiangyu; Liu, Guixi

    2016-01-01

    The cardinality balanced multi-target multi-Bernoulli (CBMeMBer) filter developed recently has been proved an effective multi-target tracking (MTT) algorithm based on the random finite set (RFS) theory, and it can jointly estimate the number of targets and their states from a sequence of sensor measurement sets. However, because of the existence of systematic errors in sensor measurements, the CBMeMBer filter can easily produce different levels of performance degradation. In this paper, an extended CBMeMBer filter, in which the joint probability density function of target state and systematic error is recursively estimated, is proposed to address the MTT problem based on the sensor measurements with systematic errors. In addition, an analytic implementation of the extended CBMeMBer filter is also presented for linear Gaussian models. Simulation results confirm that the proposed algorithm can track multiple targets with better performance. PMID:27589764

  9. FISST based method for multi-target tracking in the image plane of optical sensors.

    PubMed

    Xu, Yang; Xu, Hui; An, Wei; Xu, Dan

    2012-01-01

    A finite set statistics (FISST)-based method is proposed for multi-target tracking in the image plane of optical sensors. The method involves using signal amplitude information in probability hypothesis density (PHD) filter which is derived from FISST to improve multi-target tracking performance. The amplitude of signals generated by the optical sensor is modeled first, from which the amplitude likelihood ratio between target and clutter is derived. An alternative approach is adopted for the situations where the signal noise ratio (SNR) of target is unknown. Then the PHD recursion equations incorporated with signal information are derived and the Gaussian mixture (GM) implementation of this filter is given. Simulation results demonstrate that the proposed method achieves significantly better performance than the generic PHD filter. Moreover, our method has much lower computational complexity in the scenario with high SNR and dense clutter. PMID:22736984

  10. FISST Based Method for Multi-Target Tracking in the Image Plane of Optical Sensors

    PubMed Central

    Xu, Yang; Xu, Hui; An, Wei; Xu, Dan

    2012-01-01

    A finite set statistics (FISST)-based method is proposed for multi-target tracking in the image plane of optical sensors. The method involves using signal amplitude information in probability hypothesis density (PHD) filter which is derived from FISST to improve multi-target tracking performance. The amplitude of signals generated by the optical sensor is modeled first, from which the amplitude likelihood ratio between target and clutter is derived. An alternative approach is adopted for the situations where the signal noise ratio (SNR) of target is unknown. Then the PHD recursion equations incorporated with signal information are derived and the Gaussian mixture (GM) implementation of this filter is given. Simulation results demonstrate that the proposed method achieves significantly better performance than the generic PHD filter. Moreover, our method has much lower computational complexity in the scenario with high SNR and dense clutter. PMID:22736984

  11. A detection method for infrared multi-target in aerospace backgound

    NASA Astrophysics Data System (ADS)

    Wang, Ningming; Zhang, Yazhou

    2015-11-01

    Main task of the infrared search and track system is analyzing and identifying targets of airspace. But first this is needed to detect all targets in infrared image. Therefore, the multi-target detection algorithms are studied and we propose an effective multi-target detection method. Firstly, an improved morphological operator is designed based on airspace background and target traits of infrared image. Background is weakened but targets are enhanced when infrared image is processed by the gray morphological filter. Then, potential targets are found by the maximum local sum algorithm. Finally, true targets are affirmed based on data association of sequence images. The infrared images got from long-wavelength infrared camera are processed with the method of the paper. Experiment results show that the method can detect targets in infrared image quickly and accurately.

  12. Microfluidic immunomagnetic multi-target sorting--a model for controlling deflection of paramagnetic beads.

    PubMed

    Tsai, Scott S H; Griffiths, Ian M; Stone, Howard A

    2011-08-01

    We describe a microfluidic system that uses a magnetic field to sort paramagnetic beads by deflecting them in the direction normal to the flow. In the experiments we systematically study the dependence of the beads' deflection on bead size and susceptibility, magnet strength, fluid speed and viscosity, and device geometry. We also develop a design parameter that can aid in the design of microfluidic devices for immunomagnetic multi-target sorting. PMID:21677937

  13. Dielectrophoresis-based classification of cells using multi-target multiple-hypothesis tracking.

    PubMed

    Dickerson, Samuel J; Chiarulli, Donald M; Levitan, Steven P; Carthel, Craig; Coraluppi, Stefano

    2014-01-01

    In this paper we present a novel methodology for classifying cells by using a combination of dielectrophoresis, image tracking and classification algorithms. We use dielectrophoresis to induce unique motion patterns in cells of interest. Motion is extracted via multi-target multiple-hypothesis tracking. Trajectories are then used to classify cells based on a generalized likelihood ratio test. We present results of a simulation study and of our prototype tracking the dielectrophoretic velocities of cells. PMID:25570230

  14. Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

    PubMed Central

    Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

    2013-01-01

    Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

  15. The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect.

    PubMed

    Chu, Shifeng; Liu, Shaolin; Duan, Wenzhen; Cheng, Yong; Jiang, Xueying; Zhu, Chuanjiang; Tang, Kang; Wang, Runsheng; Xu, Lin; Wang, Xiaoying; Yu, Xiaoming; Wu, Kemei; Wang, Yan; Wang, Muzou; Huang, Huiyong; Zhang, Juntian

    2016-06-01

    Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca(2+) concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimer's disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca(2+) overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases. PMID:26812265

  16. Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective

    PubMed Central

    Talevi, Alan

    2015-01-01

    Multi-target drugs have raised considerable interest in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance issues. Prospective drug repositioning to treat comorbid conditions is an additional, overlooked application of multi-target ligands. While medicinal chemists usually rely on some version of the lock and key paradigm to design novel therapeutics, modern pharmacology recognizes that the mid- and long-term effects of a given drug on a biological system may depend not only on the specific ligand-target recognition events but also on the influence of the repeated administration of a drug on the cell gene signature. The design of multi-target agents usually imposes challenging restrictions on the topology or flexibility of the candidate drugs, which are briefly discussed in the present article. Finally, computational strategies to approach the identification of novel multi-target agents are overviewed. PMID:26441661

  17. Unconstrained underwater multi-target tracking in passive sonar systems using two-stage PF-based technique

    NASA Astrophysics Data System (ADS)

    Georgy, Jacques; Noureldin, Aboelmagd

    2014-03-01

    A robust particle filter (PF)-based multi-target tracking solution for passive sonar systems able to track an unknown time-varying number of multiple targets, while keeping continuous tracks of such targets, is presented in this article. PF is a nonlinear filtering technique that can accommodate arbitrary sensor characteristics, motion dynamics and noise distributions. An enhanced version of PF is employed and is called Mixture PF. The commonly used sampling/importance resampling PF samples from the prior importance density, while Mixture PF samples from both the prior and the observation likelihood. In order to be able to track an unknown time-varying number of multiple targets, two Mixture PFs are used, one for target detection and the other for tracking multiple targets, and a density-based clustering technique is used after the first filter. This article demonstrates the applicability of the proposed technique for the passive problem, which suffers from the lack of measurements and the small detection range of the buoys, especially for weak signals. A contact-level simulation was used to generate different scenarios and the performance of the proposed technique called Clustered-Mixture PF was examined with either bearing measurement only or bearing and Doppler measurements, and it demonstrated its high performance.

  18. Inferring multi-target QSAR models with taxonomy-based multi-task learning

    PubMed Central

    2013-01-01

    Background A plethora of studies indicate that the development of multi-target drugs is beneficial for complex diseases like cancer. Accurate QSAR models for each of the desired targets assist the optimization of a lead candidate by the prediction of affinity profiles. Often, the targets of a multi-target drug are sufficiently similar such that, in principle, knowledge can be transferred between the QSAR models to improve the model accuracy. In this study, we present two different multi-task algorithms from the field of transfer learning that can exploit the similarity between several targets to transfer knowledge between the target specific QSAR models. Results We evaluated the two methods on simulated data and a data set of 112 human kinases assembled from the public database ChEMBL. The relatedness between the kinase targets was derived from the taxonomy of the humane kinome. The experiments show that multi-task learning increases the performance compared to training separate models on both types of data given a sufficient similarity between the tasks. On the kinase data, the best multi-task approach improved the mean squared error of the QSAR models of 58 kinase targets. Conclusions Multi-task learning is a valuable approach for inferring multi-target QSAR models for lead optimization. The application of multi-task learning is most beneficial if knowledge can be transferred from a similar task with a lot of in-domain knowledge to a task with little in-domain knowledge. Furthermore, the benefit increases with a decreasing overlap between the chemical space spanned by the tasks. PMID:23842210

  19. Multi-target-qubit unconventional geometric phase gate in a multi-cavity system

    NASA Astrophysics Data System (ADS)

    Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

    2016-02-01

    Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

  20. Multi-target-qubit unconventional geometric phase gate in a multi-cavity system.

    PubMed

    Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

    2016-01-01

    Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits. PMID:26898176

  1. Network Pharmacology Strategies Toward Multi-Target Anticancer Therapies: From Computational Models to Experimental Design Principles

    PubMed Central

    Tang, Jing; Aittokallio, Tero

    2014-01-01

    Polypharmacology has emerged as novel means in drug discovery for improving treatment response in clinical use. However, to really capitalize on the polypharmacological effects of drugs, there is a critical need to better model and understand how the complex interactions between drugs and their cellular targets contribute to drug efficacy and possible side effects. Network graphs provide a convenient modeling framework for dealing with the fact that most drugs act on cellular systems through targeting multiple proteins both through on-target and off-target binding. Network pharmacology models aim at addressing questions such as how and where in the disease network should one target to inhibit disease phenotypes, such as cancer growth, ideally leading to therapies that are less vulnerable to drug resistance and side effects by means of attacking the disease network at the systems level through synergistic and synthetic lethal interactions. Since the exponentially increasing number of potential drug target combinations makes pure experimental approach quickly unfeasible, this review depicts a number of computational models and algorithms that can effectively reduce the search space for determining the most promising combinations for experimental evaluation. Such computational-experimental strategies are geared toward realizing the full potential of multi-target treatments in different disease phenotypes. Our specific focus is on system-level network approaches to polypharmacology designs in anticancer drug discovery, where we give representative examples of how network-centric modeling may offer systematic strategies toward better understanding and even predicting the phenotypic responses to multi-target therapies.

  2. ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy

    PubMed Central

    Marco-Contelles, José; Unzeta, Mercedes; Bolea, Irene; Esteban, Gerard; Ramsay, Rona R.; Romero, Alejandro; Martínez-Murillo, Ricard; Carreiras, M. Carmo; Ismaili, Lhassane

    2016-01-01

    Highlights: ASS2324 is a hybrid compound resulting from the juxtaposition of donepezil and the propargylamine PF9601NASS2324 is a multi-target directed propargylamine able to bind to all the AChE/BuChE and MAO A/B enzymesASS2324 shows antioxidant, neuroprotective and suitable permeability propertiesASS2324 restores the scopolamine-induced cognitive impairment to the same extent as donepezil, and is less toxicASS2324 prevents β-amyloid induced aggregation in the cortex of double transgenic miceASS2324 is the most advanced anti-Alzheimer agent for pre-clinical studies that we have identified in our laboratories The complex nature of Alzheimer's disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines (MTDP) showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase (MAO) inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aβ-aggregation, and possessing antioxidant and neuroprotective properties. PMID:27445665

  3. Multi-target-qubit unconventional geometric phase gate in a multi-cavity system

    PubMed Central

    Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

    2016-01-01

    Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits. PMID:26898176

  4. PMHT Approach for Multi-Target Multi-Sensor Sonar Tracking in Clutter

    PubMed Central

    Li, Xiaohua; Li, Yaan; Yu, Jing; Chen, Xiao; Dai, Miao

    2015-01-01

    Multi-sensor sonar tracking has many advantages, such as the potential to reduce the overall measurement uncertainty and the possibility to hide the receiver. However, the use of multi-target multi-sensor sonar tracking is challenging because of the complexity of the underwater environment, especially the low target detection probability and extremely large number of false alarms caused by reverberation. In this work, to solve the problem of multi-target multi-sensor sonar tracking in the presence of clutter, a novel probabilistic multi-hypothesis tracker (PMHT) approach based on the extended Kalman filter (EKF) and unscented Kalman filter (UKF) is proposed. The PMHT can efficiently handle the unknown measurements-to-targets and measurements-to-transmitters data association ambiguity. The EKF and UKF are used to deal with the high degree of nonlinearity in the measurement model. The simulation results show that the proposed algorithm can improve the target tracking performance in a cluttered environment greatly, and its computational load is low. PMID:26561817

  5. PMHT Approach for Multi-Target Multi-Sensor Sonar Tracking in Clutter.

    PubMed

    Li, Xiaohua; Li, Yaan; Yu, Jing; Chen, Xiao; Dai, Miao

    2015-01-01

    Multi-sensor sonar tracking has many advantages, such as the potential to reduce the overall measurement uncertainty and the possibility to hide the receiver. However, the use of multi-target multi-sensor sonar tracking is challenging because of the complexity of the underwater environment, especially the low target detection probability and extremely large number of false alarms caused by reverberation. In this work, to solve the problem of multi-target multi-sensor sonar tracking in the presence of clutter, a novel probabilistic multi-hypothesis tracker (PMHT) approach based on the extended Kalman filter (EKF) and unscented Kalman filter (UKF) is proposed. The PMHT can efficiently handle the unknown measurements-to-targets and measurements-to-transmitters data association ambiguity. The EKF and UKF are used to deal with the high degree of nonlinearity in the measurement model. The simulation results show that the proposed algorithm can improve the target tracking performance in a cluttered environment greatly, and its computational load is low. PMID:26561817

  6. Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

    PubMed

    Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

    2016-03-01

    To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients. PMID:27134306

  7. Behavior-based cooperative robotics applied to multi-target observation

    SciTech Connect

    Parker, L.E.

    1996-12-31

    An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring (or observing) the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement - determining where sensors should be located to maintain the targets in view. In complex applications involving limited-range sensors, the use of multiple sensors dynamically moving over time is required. In this paper, the author investigates the use of a cooperative team of autonomous sensor-based robots for the observation of multiple moving targets. The author focuses primarily on developing the distributed control strategies that allow the robot team to attempt to minimize the total time in which targets escape observation by some robot team member in the area of interest. The initial efforts on this problem address the aspects of distributed control in homogeneous robot teams with equivalent sensing and movement capabilities working in an uncluttered, bounded area. This paper first formalizes the problem, discusses related work, and then shows that this problem is NP-hard. The author then presents a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level control. The low-level control is described in terms of force fields emanating from the targets and the robots. The higher level control is presented in the ALLIANCE formalism, which provides mechanisms for fault tolerant cooperative control, and allows robot team members to adjust their low-level actions based upon the actions of their teammates. The author then presents the results of the ongoing implementation of this approach, both in simulation and on physical robots. To the authors knowledge, this is the first paper addressing this research problem that has been implemented on physical robot teams.

  8. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    PubMed

    Huang, Ling; Zhang, Wenjun; Zhang, Xiaohua; Yin, Lei; Chen, Bangyin; Song, Jinchun

    2015-11-15

    The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment. PMID:26483200

  9. Improved Bearings-Only Multi-Target Tracking with GM-PHD Filtering.

    PubMed

    Zhang, Qian; Song, Taek Lyul

    2016-01-01

    In this paper, an improved nonlinear Gaussian mixture probability hypothesis density (GM-PHD) filter is proposed to address bearings-only measurements in multi-target tracking. The proposed method, called the Gaussian mixture measurements-probability hypothesis density (GMM-PHD) filter, not only approximates the posterior intensity using a Gaussian mixture, but also models the likelihood function with a Gaussian mixture instead of a single Gaussian distribution. Besides, the target birth model of the GMM-PHD filter is assumed to be partially uniform instead of a Gaussian mixture. Simulation results show that the proposed filter outperforms the GM-PHD filter embedded with the extended Kalman filter (EKF) and the unscented Kalman filter (UKF). PMID:27626423

  10. [Possibilities for inhibiting tumor-induced angiogenesis: results with multi-target tyrosine kinase inhibitors].

    PubMed

    Török, Szilvia; Döme, Balázs

    2012-03-01

    Functional blood vasculature is essential for tumor progression. The main signalization pathways that play a key role in the survival and growth of tumor vessels originate from the VEGF-, PDGF- and FGF tyrosine kinase receptors. In the past decade, significant results have been published on receptor tyrosine kinase inhibitors (RTKIs). In this paper, the mechanisms of action and the results so far available of experimental and clinical studies on multi-target antiangiogenic TKIs are discussed. On the one hand, notable achievements have been made recently and these drugs are already used in clinical practice in some patient populations. On the other hand, the optimal combination and dosage of these drugs, selection of the apropriate biomarker and better understanding of the conflicting role of PDGFR and FGFR signaling in angiogenesis remain future challenges. PMID:22403757

  11. A multi target approach to control chemical reactions in their inhomogeneous solvent environment

    NASA Astrophysics Data System (ADS)

    Keefer, Daniel; Thallmair, Sebastian; Zauleck, Julius P. P.; de Vivie-Riedle, Regina

    2015-12-01

    Shaped laser pulses offer a powerful tool to manipulate molecular quantum systems. Their application to chemical reactions in solution is a promising concept to redesign chemical synthesis. Along this road, theoretical developments to include the solvent surrounding are necessary. An appropriate theoretical treatment is helpful to understand the underlying mechanisms. In our approach we simulate the solvent by randomly selected snapshots from molecular dynamics trajectories. We use multi target optimal control theory to optimize pulses for the various arrangements of explicit solvent molecules simultaneously. This constitutes a major challenge for the control algorithm, as the solvent configurations introduce a large inhomogeneity to the potential surfaces. We investigate how the algorithm handles the new challenges and how well the controllability of the system is preserved with increasing complexity. Additionally, we introduce a way to statistically estimate the efficiency of the optimized laser pulses in the complete thermodynamical ensemble.

  12. Multi-Target Strategy and Experimental Studies of Traditional Chinese Medicine for Alzheimer's Disease Therapy.

    PubMed

    Li, Lin; Zhang, Lan; Yang, Cui-cui

    2016-01-01

    Alzheimer's disease (AD) is a multifactorial complex disease. The pathogenesis of AD is very complicated, and involves the β-amyloid (Aβ) cascade, tau hyperphosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, reduced levels of neurotrophic factors, and damage and loss of synapses as well as cholinergic neurons. The multi-target characteristics of traditional Chinese medicine (TCM) may be advantageous over single-target drugs in the treatment of complex diseases. These drugs have therefore attracted more attention in the research and development of AD therapies. This review describes advances made in experimental studies of TCM for AD treatment. It discusses research, from our group and other laboratories, on TCM compound drugs (Shenwu capsule) and approximately 10 Chinese medicinal herb extracts (tetrahydroxystilbene glucoside, epimedium flavonoid, icariin, cornel iridoid glycoside, ginsenoside, puerarin, clausenamide, huperzine A, and timosaponins). PMID:26268330

  13. AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders

    PubMed Central

    Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya

    2016-01-01

    Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

  14. A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

    PubMed Central

    Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

    2011-01-01

    Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for

  15. [Development of multi-target multi-spectral high-speed pyrometer].

    PubMed

    Xiao, Peng; Dai, Jing-Min; Wang, Qing-Wei

    2008-11-01

    The plume temperature of a solid propellant rocket engine (SPRE) is a fundamental parameter in denoting combustion status. It is necessary to measure the temperature along both the axis and the radius of the engine. In order to measure the plume temperature distribution of a solid propellant rocket engine, the multi-spectral thermometry has been approved. Previously the pyrometer was developed in the Harbin Institute of Technology of China in 1999, which completed the measurement of SPRE plume temperature and its distribution with multi-spectral technique in aerospace model development for the first time. Following this experience, a new type of multi-target multi-spectral high-speed pyrometer used in the ground experiments of SPRE plume temperature measurement was developed. The main features of the instrument include the use of a dispersing prism and a photo-diode array to cover the entire spectral band of 0.4 to 1.1 microm. The optic fibers are used in order to collect and transmit the thermal radiation fluxes. The instrument can measure simultaneously the temperature and emissivity of eight spectra for six uniformly distributed points on the target surface, which are well defined by the hole on the field stop lens. A specially designed S/H (Sample/Hold) circuit, with 48 sample and hold units that were triggered with a signal, measures the multi-spectral and multi-target outputs. It can sample 48 signals with a less than 10ns time difference which is most important for the temperature calculation. PMID:19271529

  16. AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

    PubMed

    Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

    2016-05-25

    Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

  17. A Novel Square-Root Cubature Information Weighted Consensus Filter Algorithm for Multi-Target Tracking in Distributed Camera Networks

    PubMed Central

    Chen, Yanming; Zhao, Qingjie

    2015-01-01

    This paper deals with the problem of multi-target tracking in a distributed camera network using the square-root cubature information filter (SCIF). SCIF is an efficient and robust nonlinear filter for multi-sensor data fusion. In camera networks, multiple cameras are arranged in a dispersed manner to cover a large area, and the target may appear in the blind area due to the limited field of view (FOV). Besides, each camera might receive noisy measurements. To overcome these problems, this paper proposes a novel multi-target square-root cubature information weighted consensus filter (MTSCF), which reduces the effect of clutter or spurious measurements using joint probabilistic data association (JPDA) and proper weights on the information matrix and information vector. The simulation results show that the proposed algorithm can efficiently track multiple targets in camera networks and is obviously better in terms of accuracy and stability than conventional multi-target tracking algorithms. PMID:25951338

  18. A novel square-root cubature information weighted consensus filter algorithm for multi-target tracking in distributed camera networks.

    PubMed

    Chen, Yanming; Zhao, Qingjie

    2015-01-01

    This paper deals with the problem of multi-target tracking in a distributed camera network using the square-root cubature information filter (SCIF). SCIF is an efficient and robust nonlinear filter for multi-sensor data fusion. In camera networks, multiple cameras are arranged in a dispersed manner to cover a large area, and the target may appear in the blind area due to the limited field of view (FOV). Besides, each camera might receive noisy measurements. To overcome these problems, this paper proposes a novel multi-target square-root cubature information weighted consensus filter (MTSCF), which reduces the effect of clutter or spurious measurements using joint probabilistic data association (JPDA) and proper weights on the information matrix and information vector. The simulation results show that the proposed algorithm can efficiently track multiple targets in camera networks and is obviously better in terms of accuracy and stability than conventional multi-target tracking algorithms. PMID:25951338

  19. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    PubMed Central

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  20. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

    PubMed

    Ferreira, Nelson; Gonçalves, Nádia P; Saraiva, Maria J; Almeida, Maria R

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis. PMID:27197872

  1. In Vitro and In Vivo Activity of Multi-Target Inhibitors Against Trypanosoma brucei

    PubMed Central

    Yang, Gyongseon; Zhu, Wei; Wang, Yang; Huang, Guozhong; Byun, Sooyoung; Choi, Gahee; Li, Kai; Huang, Zhuoli; Docampo, Roberto; Oldfield, Eric; No, Joo Hwan

    2015-01-01

    We tested a series of amidine and related compounds against Trypanosoma brucei. The most active compound was a biphenyldiamidine which had an EC50 of 7.7 nM against bloodstream form parasites. There was little toxicity against two human cell lines with CC50 > 100 μM. There was also good in vivo activity in a mouse model of infection with 100% survival at 3 mg/kg i.p. The most potent lead blocked replication of kinetoplast DNA (k-DNA), but not nuclear DNA, in the parasite. Some compounds also inhibited the enzyme farnesyl diphosphate synthase (FPPS) and some were uncouplers of oxidative phosphorylation. We developed a computational model for T. brucei cell growth inhibition (R2 = 0.76) using DNA ΔTm values for inhibitor binding, combined with T. brucei FPPS IC50 values. Overall, the results suggest that it may be possible to develop multi-target drug leads against T. brucei that act by inhibiting both k-DNA replication and isoprenoid biosynthesis. PMID:26295062

  2. Topology of classical molecular optimal control landscapes for multi-target objectives

    SciTech Connect

    Joe-Wong, Carlee; Ho, Tak-San; Rabitz, Herschel; Wu, Rebing

    2015-04-21

    This paper considers laser-driven optimal control of an ensemble of non-interacting molecules whose dynamics lie in classical phase space. The molecules evolve independently under control to distinct final states. We consider a control landscape defined in terms of multi-target (MT) molecular states and analyze the landscape as a functional of the control field. The topology of the MT control landscape is assessed through its gradient and Hessian with respect to the control. Under particular assumptions, the MT control landscape is found to be free of traps that could hinder reaching the objective. The Hessian associated with an optimal control field is shown to have finite rank, indicating an inherent degree of robustness to control noise. Both the absence of traps and rank of the Hessian are shown to be analogous to the situation of specifying multiple targets for an ensemble of quantum states. Numerical simulations are presented to illustrate the classical landscape principles and further characterize the system behavior as the control field is optimized.

  3. ATP as a multi-target danger signal in the brain

    PubMed Central

    Rodrigues, Ricardo J.; Tomé, Angelo R.; Cunha, Rodrigo A.

    2015-01-01

    ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, in astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses. This involves the activation of different ATP P2 receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases. Notably, brain noxious stimuli trigger a sustained increase of extracellular ATP, which plays a key role as danger signal in the brain. This involves a combined action of extracellular ATP in different cell types, namely increasing the susceptibility of neurons to damage, promoting astrogliosis and recruiting and formatting microglia to mount neuroinflammatory responses. Such actions involve the activation of different receptors, as heralded by neuroprotective effects resulting from blockade mainly of P2X7R, P2Y1R and adenosine A2A receptors (A2AR), which hierarchy, cooperation and/or redundancy is still not resolved. These pleiotropic functions of ATP as a danger signal in brain damage prompt a therapeutic interest to multi-target different purinergic receptors to provide maximal opportunities for neuroprotection. PMID:25972780

  4. Multi-target camera tracking, hand-off and display LDRD 158819 final report

    SciTech Connect

    Anderson, Robert J.

    2014-10-01

    Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldnt lead to more alarms, more monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that takes live video imagery from multiple video cameras, identifies individual moving targets from the background imagery, and then displays the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of currently capability.

  5. Multi-target camera tracking, hand-off and display LDRD 158819 final report.

    SciTech Connect

    Anderson, Robert J.

    2014-10-01

    Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldnt lead to more alarms, more monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that takes live video imagery from multiple video cameras, identifies individual moving targets from the background imagery, and then displays the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of currently capability.

  6. UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting therapy of brain glioma.

    PubMed

    Zhang, Bo; Zhang, Yujie; Liao, Ziwei; Jiang, Ting; Zhao, Jingjing; Tuo, Yanyan; She, Xiaojian; Shen, Shun; Chen, Jun; Zhang, Qizhi; Jiang, Xinguo; Hu, Yu; Pang, Zhiqing

    2015-01-01

    Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy. PMID:25443789

  7. Crawling and walking infants encounter objects differently in a multi-target environment.

    PubMed

    Dosso, Jill A; Boudreau, J Paul

    2014-10-01

    From birth, infants move their bodies in order to obtain information and stimulation from their environment. Exploratory movements are important for the development of an infant's understanding of the world and are well established as being key to cognitive advances. Newly acquired motor skills increase the potential actions available to the infant. However, the way that infants employ potential actions in environments with multiple potential targets is undescribed. The current work investigated the target object selections of infants across a range of self-produced locomotor experience (11- to 14-month-old crawlers and walkers). Infants repeatedly accessed objects among pairs of objects differing in both distance and preference status, some requiring locomotion. Overall, their object actions were found to be sensitive to object preference status; however, the role of object distance in shaping object encounters was moderated by movement status. Crawlers' actions appeared opportunistic and were biased towards nearby objects while walkers' actions appeared intentional and were independent of object position. Moreover, walkers' movements favoured preferred objects more strongly for children with higher levels of self-produced locomotion experience. The multi-target experimental situation used in this work parallels conditions faced by foraging organisms, and infants' behaviours were discussed with respect to optimal foraging theory. There is a complex interplay between infants' agency, locomotor experience, and environment in shaping their motor actions. Infants' movements, in turn, determine the information and experiences offered to infants by their micro-environment. PMID:24888534

  8. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

    PubMed Central

    Ferreira, Nelson; Gonçalves, Nádia P.; Saraiva, Maria J.; Almeida, Maria R.

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis. PMID:27197872

  9. Molecular Investigations of Protriptyline as a Multi-Target Directed Ligand in Alzheimer's Disease

    PubMed Central

    Bansode, Sneha B.; Jana, Asis K.; Batkulwar, Kedar B.; Warkad, Shrikant D.; Joshi, Rakesh S.; Sengupta, Neelanjana; Kulkarni, Mahesh J.

    2014-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE), β-secretase (BACE-1), and amyloid β (Aβ) aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment. PMID:25141174

  10. Gait Measurement System for the Multi-Target Stepping Task Using a Laser Range Sensor

    PubMed Central

    Yorozu, Ayanori; Nishiguchi, Shu; Yamada, Minoru; Aoyama, Tomoki; Moriguchi, Toshiki; Takahashi, Masaki

    2015-01-01

    For the prevention of falling in the elderly, gait training has been proposed using tasks such as the multi-target stepping task (MTST), in which participants step on assigned colored targets. This study presents a gait measurement system using a laser range sensor for the MTST to evaluate the risk of falling. The system tracks both legs and measures general walking parameters such as stride length and walking speed. Additionally, it judges whether the participant steps on the assigned colored targets and detects cross steps to evaluate cognitive function. However, situations in which one leg is hidden from the sensor or the legs are close occur and are likely to lead to losing track of the legs or false tracking. To solve these problems, we propose a novel leg detection method with five observed leg patterns and global nearest neighbor-based data association with a variable validation region based on the state of each leg. In addition, methods to judge target steps and detect cross steps based on leg trajectory are proposed. From the experimental results with the elderly, it is confirmed that the proposed system can improve leg-tracking performance, judge target steps and detect cross steps with high accuracy. PMID:25985161

  11. ATP as a multi-target danger signal in the brain.

    PubMed

    Rodrigues, Ricardo J; Tomé, Angelo R; Cunha, Rodrigo A

    2015-01-01

    ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, in astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses. This involves the activation of different ATP P2 receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases. Notably, brain noxious stimuli trigger a sustained increase of extracellular ATP, which plays a key role as danger signal in the brain. This involves a combined action of extracellular ATP in different cell types, namely increasing the susceptibility of neurons to damage, promoting astrogliosis and recruiting and formatting microglia to mount neuroinflammatory responses. Such actions involve the activation of different receptors, as heralded by neuroprotective effects resulting from blockade mainly of P2X7R, P2Y1R and adenosine A2A receptors (A2AR), which hierarchy, cooperation and/or redundancy is still not resolved. These pleiotropic functions of ATP as a danger signal in brain damage prompt a therapeutic interest to multi-target different purinergic receptors to provide maximal opportunities for neuroprotection. PMID:25972780

  12. Joint decision and Naive Bayes learning for detection of space multi-target

    NASA Astrophysics Data System (ADS)

    Huang, Tao; Li, Zhulian; Zhou, Yu; Xiong, Yaoheng; Zhang, Haitao

    2014-07-01

    In the photoelectric tracking system, the detection of space multi-target is crucial for target localization and tracking. The difficulties include the interferences from CCD smear and strong noise, the few characteristics of spot-like targets and the challenge of multiple targets. In this paper, we propose a hybrid algorithm of joint decision and Naive Bayes (JD-NB) learning, and present the duty ratio feature to discriminate the target and smear blocks. Firstly, we extract the proper features and train the parameters of the Naive Bayes classifier. Secondly, target blocks are preliminarily estimated with the Naive Bayes. Lastly, the 4-adjacent blocks of the candidate target blocks are jointed to analyze the distribution pattern and the true target blocks are secondarily extracted by the method of pattern matching. Experimental results indicate that the proposed JD-NB algorithm not only possesses a high recognition rate of better than 90% for the target block, but also effectively overcomes the disturbance of the smear block. Moreover, it performs well in the detection of small and faint targets when the SNR of the block is higher than about 0.014.

  13. Antenna Allocation in MIMO Radar with Widely Separated Antennas for Multi-Target Detection

    PubMed Central

    Gao, Hao; Wang, Jian; Jiang, Chunxiao; Zhang, Xudong

    2014-01-01

    In this paper, we explore a new resource called multi-target diversity to optimize the performance of multiple input multiple output (MIMO) radar with widely separated antennas for detecting multiple targets. In particular, we allocate antennas of the MIMO radar to probe different targets simultaneously in a flexible manner based on the performance metric of relative entropy. Two antenna allocation schemes are proposed. In the first scheme, each antenna is allocated to illuminate a proper target over the entire illumination time, so that the detection performance of each target is guaranteed. The problem is formulated as a minimum makespan scheduling problem in the combinatorial optimization framework. Antenna allocation is implemented through a branch-and-bound algorithm and an enhanced factor 2 algorithm. In the second scheme, called antenna-time allocation, each antenna is allocated to illuminate different targets with different illumination time. Both antenna allocation and time allocation are optimized based on illumination probabilities. Over a large range of transmitted power, target fluctuations and target numbers, both of the proposed antenna allocation schemes outperform the scheme without antenna allocation. Moreover, the antenna-time allocation scheme achieves a more robust detection performance than branch-and-bound algorithm and the enhanced factor 2 algorithm when the target number changes. PMID:25350505

  14. Gait measurement system for the multi-target stepping task using a laser range sensor.

    PubMed

    Yorozu, Ayanori; Nishiguchi, Shu; Yamada, Minoru; Aoyama, Tomoki; Moriguchi, Toshiki; Takahashi, Masaki

    2015-01-01

    For the prevention of falling in the elderly, gait training has been proposed using tasks such as the multi-target stepping task (MTST), in which participants step on assigned colored targets. This study presents a gait measurement system using a laser range sensor for the MTST to evaluate the risk of falling. The system tracks both legs and measures general walking parameters such as stride length and walking speed. Additionally, it judges whether the participant steps on the assigned colored targets and detects cross steps to evaluate cognitive function. However, situations in which one leg is hidden from the sensor or the legs are close occur and are likely to lead to losing track of the legs or false tracking. To solve these problems, we propose a novel leg detection method with five observed leg patterns and global nearest neighbor-based data association with a variable validation region based on the state of each leg. In addition, methods to judge target steps and detect cross steps based on leg trajectory are proposed. From the experimental results with the elderly, it is confirmed that the proposed system can improve leg-tracking performance, judge target steps and detect cross steps with high accuracy. PMID:25985161

  15. Multi-Target Tracking With Time-Varying Clutter Rate and Detection Profile: Application to Time-Lapse Cell Microscopy Sequences.

    PubMed

    Rezatofighi, Seyed Hamid; Gould, Stephen; Vo, Ba Tuong; Vo, Ba-Ngu; Mele, Katarina; Hartley, Richard

    2015-06-01

    Quantitative analysis of the dynamics of tiny cellular and sub-cellular structures, known as particles, in time-lapse cell microscopy sequences requires the development of a reliable multi-target tracking method capable of tracking numerous similar targets in the presence of high levels of noise, high target density, complex motion patterns and intricate interactions. In this paper, we propose a framework for tracking these structures based on the random finite set Bayesian filtering framework. We focus on challenging biological applications where image characteristics such as noise and background intensity change during the acquisition process. Under these conditions, detection methods usually fail to detect all particles and are often followed by missed detections and many spurious measurements with unknown and time-varying rates. To deal with this, we propose a bootstrap filter composed of an estimator and a tracker. The estimator adaptively estimates the required meta parameters for the tracker such as clutter rate and the detection probability of the targets, while the tracker estimates the state of the targets. Our results show that the proposed approach can outperform state-of-the-art particle trackers on both synthetic and real data in this regime. PMID:25594963

  16. Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration

    PubMed Central

    Ramsay, Rona R.; Majekova, Magdalena; Medina, Milagros; Valoti, Massimo

    2016-01-01

    HIGHLIGHTS Compounds that interact with multiple targets but minimally with the cytochrome P450 system (CYP) address the many factors leading to neurodegeneration.Acetyl- and Butyryl-cholineEsterases (AChE, BChE) and Monoamine Oxidases A/B (MAO A, MAO B) are targets for Multi-Target Designed Ligands (MTDL).ASS234 is an irreversible inhibitor of MAO A >MAO B and has micromolar potency against the cholinesterases.ASS234 is a poor CYP substrate in human liver, yielding the depropargylated metabolite.SMe1EC2, a stobadine derivative, showed high radical scavenging property, in vitro and in vivo giving protection in head trauma and diabetic damage of endothelium.Control of mitochondrial function and morphology by manipulating fission and fusion is emerging as a target area for therapeutic strategies to decrease the pathological outcome of neurodegenerative diseases. Growing evidence supports the view that neurodegenerative diseases have multiple and common mechanisms in their aetiologies. These multifactorial aspects have changed the broadly common assumption that selective drugs are superior to “dirty drugs” for use in therapy. This drives the research in studies of novel compounds that might have multiple action mechanisms. In neurodegeneration, loss of neuronal signaling is a major cause of the symptoms, so preservation of neurotransmitters by inhibiting the breakdown enzymes is a first approach. Acetylcholinesterase (AChE) inhibitors are the drugs preferentially used in AD and that one of these, rivastigmine, is licensed also for PD. Several studies have shown that monoamine oxidase (MAO) B, located mainly in glial cells, increases with age and is elevated in Alzheimer (AD) and Parkinson's Disease's (PD). Deprenyl, a MAO B inhibitor, significantly delays the initiation of levodopa treatment in PD patients. These indications underline that AChE and MAO are considered a necessary part of multi-target designed ligands (MTDL). However, both of these targets are

  17. Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration.

    PubMed

    Ramsay, Rona R; Majekova, Magdalena; Medina, Milagros; Valoti, Massimo

    2016-01-01

    HIGHLIGHTS Compounds that interact with multiple targets but minimally with the cytochrome P450 system (CYP) address the many factors leading to neurodegeneration.Acetyl- and Butyryl-cholineEsterases (AChE, BChE) and Monoamine Oxidases A/B (MAO A, MAO B) are targets for Multi-Target Designed Ligands (MTDL).ASS234 is an irreversible inhibitor of MAO A >MAO B and has micromolar potency against the cholinesterases.ASS234 is a poor CYP substrate in human liver, yielding the depropargylated metabolite.SMe1EC2, a stobadine derivative, showed high radical scavenging property, in vitro and in vivo giving protection in head trauma and diabetic damage of endothelium.Control of mitochondrial function and morphology by manipulating fission and fusion is emerging as a target area for therapeutic strategies to decrease the pathological outcome of neurodegenerative diseases. Growing evidence supports the view that neurodegenerative diseases have multiple and common mechanisms in their aetiologies. These multifactorial aspects have changed the broadly common assumption that selective drugs are superior to "dirty drugs" for use in therapy. This drives the research in studies of novel compounds that might have multiple action mechanisms. In neurodegeneration, loss of neuronal signaling is a major cause of the symptoms, so preservation of neurotransmitters by inhibiting the breakdown enzymes is a first approach. Acetylcholinesterase (AChE) inhibitors are the drugs preferentially used in AD and that one of these, rivastigmine, is licensed also for PD. Several studies have shown that monoamine oxidase (MAO) B, located mainly in glial cells, increases with age and is elevated in Alzheimer (AD) and Parkinson's Disease's (PD). Deprenyl, a MAO B inhibitor, significantly delays the initiation of levodopa treatment in PD patients. These indications underline that AChE and MAO are considered a necessary part of multi-target designed ligands (MTDL). However, both of these targets are simply

  18. Selenium induces a multi-targeted cell death process in addition to ROS formation.

    PubMed

    Wallenberg, Marita; Misra, Sougat; Wasik, Agata M; Marzano, Cristina; Björnstedt, Mikael; Gandin, Valentina; Fernandes, Aristi P

    2014-04-01

    Selenium compounds inhibit neoplastic growth. Redox active selenium compounds are evolving as promising chemotherapeutic agents through tumour selectivity and multi-target response, which are of great benefit in preventing development of drug resistance. Generation of reactive oxygen species is implicated in selenium-mediated cytotoxic effects on cancer cells. Recent findings indicate that activation of diverse intracellular signalling leading to cell death depends on the chemical form of selenium applied and/or cell line investigated. In the present study, we aimed at deciphering different modes of cell death in a single cell line (HeLa) upon treatment with three redox active selenium compounds (selenite, selenodiglutathione and seleno-DL-cystine). Both selenite and selenodiglutathione exhibited equipotent toxicity (IC50 5 μM) in these cells with striking differences in toxicity mechanisms. Morphological and molecular alterations provided evidence of necroptosis-like cell death in selenite treatment, whereas selenodiglutathione induced apoptosis-like cell death. We demonstrate that selenodiglutathione efficiently glutathionylated free protein thiols, which might explain the early differences in cytotoxic effects induced by selenite and selenodiglutathione. In contrast, seleno-DL-cystine treatment at an IC50 concentration of 100 μM induced morphologically two distinct different types of cell death, one with apoptosis-like phenotype, while the other was reminiscent of paraptosis-like cell death, characterized by induction of unfolded protein response, ER-stress and occurrence of large cytoplasmic vacuoles. Collectively, the current results underline the diverse cytotoxic effects and variable potential of redox active selenium compounds on the survival of HeLa cells and thereby substantiate the potential of chemical species-specific usage of selenium in the treatment of cancers. PMID:24400844

  19. Development of a multi-target TaqMan assay to detect eastern equine encephalitis virus variants in mosquitoes.

    PubMed

    Armstrong, Philip M; Prince, Nicholanna; Andreadis, Theodore G

    2012-10-01

    Disease outbreaks caused by eastern equine encephalitis virus (EEEV; Togaviridae, Alphavirus) may be prevented by implementing effective surveillance and intervention strategies directed against the mosquito vector. Methods for EEEV detection in mosquitoes include a real-time reverse transcriptase PCR technique (TaqMan assay), but we report its failure to detect variants isolated in Connecticut in 2011, due to a single base-pair mismatch in the probe-binding site. To improve the molecular detection of EEEV, we developed a multi-target TaqMan assay by adding a second primer/probe set to provide redundant targets for EEEV detection. The multi-target TaqMan assay had similar performance characteristics to the conventional assay, but also detected newly-evolving strains of EEEV. The approach described here increases the reliability of the TaqMan assay by creating back-up targets for virus detection without sacrificing sensitivity or specificity. PMID:22835151

  20. Experimental demonstration of a multi-target detection technique using an X-band optically steered phased array radar.

    PubMed

    Shi, Nuannuan; Li, Ming; Deng, Ye; Zhang, Lihong; Sun, Shuqian; Tang, Jian; Li, Wei; Zhu, Ninghua

    2016-06-27

    An X-band optically-steered phased array radar is developed to demonstrate high resolution multi-target detection. The beam forming is implemented based on wavelength-swept true time delay (TTD) technique. The beam forming system has a wide direction tuning range of ± 54 degree, low magnitude ripple of ± 0.5 dB and small delay error of 0.13 ps/nm. To further verify performance of the proposed optically-steered phased array radar, three experiments are then carried out to implement the single and multiple target detection. A linearly chirped X-band microwave signal is used as radar signal which is finally compressed at the receiver to improve the detection accuracy. The ranging resolution for multi-target detection is up to 2 cm within the measuring distance over 4 m and the azimuth angle error is less than 4 degree. PMID:27410597

  1. On 'polypharmacy' and multi-target agents, complementary strategies for improving the treatment of depression: a comparative appraisal.

    PubMed

    Millan, Mark J

    2014-07-01

    Major depression is a heterogeneous disorder, both in terms of symptoms, ranging from anhedonia to cognitive impairment, and in terms of pathogenesis, with many interacting genetic, epigenetic, developmental and environmental causes. Accordingly, it seems unlikely that depressive states could be fully controlled by a drug possessing one discrete mechanism of action and, in the wake of disappointing results with several classes of highly selective agent, multi-modal treatment concepts are attracting attention. As concerns pharmacotherapy, there are essentially two core strategies. First, multi-target antidepressants that act via two or more complementary mechanisms and, second, polypharmacy, which refers to co-administration of two distinct drugs, usually in separate pills. Both multi-target agents and polypharmacy ideally couple a therapeutically unexploited action to a clinically established mechanism in order to enhance efficacy, moderate side-effects, accelerate onset of action and treat a broader range of symptoms. The melatonin MT1/MT2 agonist and 5-HT(2C) antagonist, agomelatine, which is effective in the short- and long-term treatment of depression, exemplifies the former approach, while evidence-based polypharmacy is illustrated by the adjunctive use of second-generation antipsychotics with serotonin reuptake inhibitors for treatment of resistant depression. Histone acetylation and methylation, ghrelin signalling, inflammatory modulators, metabotropic glutamate-7 receptors and trace amine-associated-1 receptors comprise attractive substrates for new multi-target and polypharmaceutical strategies. The present article outlines the rationale underpinning multi-modal approaches for treating depression, and critically compares and contrasts the pros and cons of established and potentially novel multi-target vs. polypharmaceutical treatments. On balance, the former appear the most promising for the elaboration, development and clinical implementation of

  2. Proposed Methodology for Application of Human-like gradual Multi-Agent Q-Learning (HuMAQ) for Multi-robot Exploration

    NASA Astrophysics Data System (ADS)

    Narayan Ray, Dip; Majumder, Somajyoti

    2014-07-01

    Several attempts have been made by the researchers around the world to develop a number of autonomous exploration techniques for robots. But it has been always an important issue for developing the algorithm for unstructured and unknown environments. Human-like gradual Multi-agent Q-leaming (HuMAQ) is a technique developed for autonomous robotic exploration in unknown (and even unimaginable) environments. It has been successfully implemented in multi-agent single robotic system. HuMAQ uses the concept of Subsumption architecture, a well-known Behaviour-based architecture for prioritizing the agents of the multi-agent system and executes only the most common action out of all the different actions recommended by different agents. Instead of using new state-action table (Q-table) each time, HuMAQ uses the immediate past table for efficient and faster exploration. The proof of learning has also been established both theoretically and practically. HuMAQ has the potential to be used in different and difficult situations as well as applications. The same architecture has been modified to use for multi-robot exploration in an environment. Apart from all other existing agents used in the single robotic system, agents for inter-robot communication and coordination/ co-operation with the other similar robots have been introduced in the present research. Current work uses a series of indigenously developed identical autonomous robotic systems, communicating with each other through ZigBee protocol.

  3. Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease.

    PubMed

    Unzeta, Mercedes; Esteban, Gerard; Bolea, Irene; Fogel, Wieslawa A; Ramsay, Rona R; Youdim, Moussa B H; Tipton, Keith F; Marco-Contelles, José

    2016-01-01

    HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands

  4. Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease

    PubMed Central

    Unzeta, Mercedes; Esteban, Gerard; Bolea, Irene; Fogel, Wieslawa A.; Ramsay, Rona R.; Youdim, Moussa B. H.; Tipton, Keith F.; Marco-Contelles, José

    2016-01-01

    HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands

  5. Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

    PubMed

    Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

    2012-02-01

    Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority <15.4%) of the individual target inhibitors of the same target pair and 0.58-7.1% of the other 6 targets outside the target pair. COMBI-SVMs showed low dual inhibitor false hit rates (0.006-0.056%, 0.042-0.21%, 0.2-4%) in screening 17 million PubChem compounds, 168,000 MDDR compounds, and 7-8181 MDDR compounds similar to the dual inhibitors. Compared with similarity searching, k-NN and PNN methods, COMBI-SVM produced comparable dual inhibitor yields, similar target selectivity, and lower false hit rate in screening 168,000 MDDR compounds. The annotated classes of many COMBI-SVMs identified MDDR virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. PMID:22064367

  6. Evaluation of multi-target immunogenic reagents for the detection of latent and body fluid-contaminated fingermarks.

    PubMed

    Lam, Rolanda; Hofstetter, Oliver; Lennard, Chris; Roux, Claude; Spindler, Xanthe

    2016-07-01

    Fingermark enhancement reagents capable of molecular recognition offer a highly selective and sensitive method of detection. Antibodies and aptamers provide a high degree of adaptability for visualisation, allowing for the selection of the most appropriate visualisation wavelength for a particular substrate without the need for specialist equipment or image processing. However, the major hurdle to overcome is the balance between sensitivity and selectivity. Single-target molecular recognition is highly specific, purported to have better detection limits than chemical reactions or stains, and can provide information about the donor or activity, but often results in incomplete ridge pattern development. Consequently, the development and evaluation of multi-target biomolecular reagents for fingermark enhancement was investigated, with the focus on endogenous eccrine secretions. To assess the suitability of the immunogenic reagents for potential operational use, a variety of parameters (i.e., processing time, fixing and working solution conditions) were optimised on a wide range of non-porous and semi-porous substrates. The relative performance of immunogenic reagents was compared to that of routine techniques applied to latent marks and marks in blood, semen and saliva. The incorporation of these novel reagents into routine technique sequences was also investigated. The experimental results indicated that the multi-target immunogenic reagents were not a suitable alternative to routine detection methods or sequences, but may have promise as a "last resort" method for difficult substrates or cases. PMID:27174074

  7. In Vivo Characterization of ARN14140, a Memantine/Galantamine-Based Multi-Target Compound for Alzheimer's Disease.

    PubMed

    Reggiani, Angelo M; Simoni, Elena; Caporaso, Roberta; Meunier, Johann; Keller, Emeline; Maurice, Tangui; Minarini, Anna; Rosini, Michela; Cavalli, Andrea

    2016-01-01

    Alzheimer's disease (AD) is a chronic pathological condition that leads to neurodegeneration, loss of intellectual abilities, including cognition and memory, and ultimately to death. It is widely recognized that AD is a multifactorial disease, where different pathological cascades (mainly amyloid and tau) contribute to neural death and to the clinical outcome related to the disease. The currently available drugs for AD were developed according to the one-target, one-drug paradigm. In recent times, multi-target strategies have begun to play an increasingly central role in the discovery of more efficacious candidates for complex neurological conditions, including AD. In this study, we report on the in vivo pharmacological characterization of ARN14140, a new chemical entity, which was obtained through a multi-target structure-activity relationship campaign, and which showed a balanced inhibiting profile against the acetylcholinesterase enzyme and the NMDA receptor. Based on the initial promising biochemical data, ARN14140 is here studied in mice treated with the amyloidogenic fragment 25-35 of the amyloid-β peptide, a consolidated non-transgenic AD model. Sub-chronically treating animals with ARN14140 leads to a prevention of the cognitive impairment and of biomarker levels connected to neurodegeneration, demonstrating its neuroprotective potential as new AD agent. PMID:27609215

  8. Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

    NASA Astrophysics Data System (ADS)

    Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

    2016-05-01

    Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

  9. Development and application of a multi-targeting reference plasmid as calibrator for analysis of five genetically modified soybean events.

    PubMed

    Pi, Liqun; Li, Xiang; Cao, Yiwei; Wang, Canhua; Pan, Liangwen; Yang, Litao

    2015-04-01

    Reference materials are important in accurate analysis of genetically modified organism (GMO) contents in food/feeds, and development of novel reference plasmid is a new trend in the research of GMO reference materials. Herein, we constructed a novel multi-targeting plasmid, pSOY, which contained seven event-specific sequences of five GM soybeans (MON89788-5', A2704-12-3', A5547-127-3', DP356043-5', DP305423-3', A2704-12-5', and A5547-127-5') and sequence of soybean endogenous reference gene Lectin. We evaluated the specificity, limit of detection and quantification, and applicability of pSOY in both qualitative and quantitative PCR analyses. The limit of detection (LOD) was as low as 20 copies in qualitative PCR, and the limit of quantification (LOQ) in quantitative PCR was 10 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and Lectin assays were higher than 90%, and the squared regression coefficients (R(2)) were more than 0.999. The quantification bias varied from 0.21% to 19.29%, and the relative standard deviations were from 1.08% to 9.84% in simulated samples analysis. All the results demonstrated that the developed multi-targeting plasmid, pSOY, was a credible substitute of matrix reference materials, and could be used as a reliable reference calibrator in the identification and quantification of multiple GM soybean events. PMID:25673245

  10. Multi-target tacrine-coumarin hybrids: cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease.

    PubMed

    Xie, Sai-Sai; Wang, Xiaobing; Jiang, Neng; Yu, Wenying; Wang, Kelvin D G; Lan, Jin-Shuai; Li, Zhong-Rui; Kong, Ling-Yi

    2015-05-01

    A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 μM). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment. PMID:25812965

  11. In Vivo Characterization of ARN14140, a Memantine/Galantamine-Based Multi-Target Compound for Alzheimer’s Disease

    PubMed Central

    Reggiani, Angelo M.; Simoni, Elena; Caporaso, Roberta; Meunier, Johann; Keller, Emeline; Maurice, Tangui; Minarini, Anna; Rosini, Michela; Cavalli, Andrea

    2016-01-01

    Alzheimer’s disease (AD) is a chronic pathological condition that leads to neurodegeneration, loss of intellectual abilities, including cognition and memory, and ultimately to death. It is widely recognized that AD is a multifactorial disease, where different pathological cascades (mainly amyloid and tau) contribute to neural death and to the clinical outcome related to the disease. The currently available drugs for AD were developed according to the one-target, one-drug paradigm. In recent times, multi-target strategies have begun to play an increasingly central role in the discovery of more efficacious candidates for complex neurological conditions, including AD. In this study, we report on the in vivo pharmacological characterization of ARN14140, a new chemical entity, which was obtained through a multi-target structure-activity relationship campaign, and which showed a balanced inhibiting profile against the acetylcholinesterase enzyme and the NMDA receptor. Based on the initial promising biochemical data, ARN14140 is here studied in mice treated with the amyloidogenic fragment 25–35 of the amyloid-β peptide, a consolidated non-transgenic AD model. Sub-chronically treating animals with ARN14140 leads to a prevention of the cognitive impairment and of biomarker levels connected to neurodegeneration, demonstrating its neuroprotective potential as new AD agent. PMID:27609215

  12. Molecular and cellular effects of multi-targeted cyclin-dependent kinase inhibition in myeloma: biological and clinical implications.

    PubMed

    McMillin, Douglas W; Delmore, Jake; Negri, Joseph; Buon, Leutz; Jacobs, Hannah M; Laubach, Jacob; Jakubikova, Jana; Ooi, Melissa; Hayden, Patrick; Schlossman, Robert; Munshi, Nikhil C; Lengauer, Christoph; Richardson, Paul G; Anderson, Kenneth C; Mitsiades, Constantine S

    2011-02-01

    Cell cycle regulators, such as cyclin-dependent kinases (CDKs), are appealing targets for multiple myeloma (MM) therapy given the increased proliferative rates of tumour cells in advanced versus early stages of MM. We hypothesized that a multi-targeted CDK inhibitor with a different spectrum of activity compared to existing CDK inhibitors could trigger distinct molecular sequelae with therapeutic implications for MM. We therefore studied the small molecule heterocyclic compound NVP-LCQ195/AT9311 (LCQ195), which inhibits CDK1, CDK2 and CDK5, as well as CDK3 and CDK9. LCQ195 induced cell cycle arrest and eventual apoptotic cell death of MM cells, even at sub-μmol/l concentrations, spared non-malignant cells, and overcame the protection conferred to MM cells by stroma or cytokines of the bone marrow milieu. In MM cells, LCQ195 triggered decreased amplitude of transcriptional signatures associated with oncogenesis, drug resistance and stem cell renewal, including signatures of activation of key transcription factors for MM cells e.g. myc, HIF-1α, IRF4. Bortezomib-treated MM patients whose tumours had high baseline expression of genes suppressed by LCQ195 had significantly shorter progression-free and overall survival than those with low levels of these transcripts in their MM cells. These observations provide insight into the biological relevance of multi-targeted CDK inhibition in MM. PMID:21223249

  13. An Intelligent Man-Machine Interface—Multi-Robot Control Adapted for Task Engagement Based on Single-Trial Detectability of P300

    PubMed Central

    Kirchner, Elsa A.; Kim, Su K.; Tabie, Marc; Wöhrle, Hendrik; Maurus, Michael; Kirchner, Frank

    2016-01-01

    Advanced man-machine interfaces (MMIs) are being developed for teleoperating robots at remote and hardly accessible places. Such MMIs make use of a virtual environment and can therefore make the operator immerse him-/herself into the environment of the robot. In this paper, we present our developed MMI for multi-robot control. Our MMI can adapt to changes in task load and task engagement online. Applying our approach of embedded Brain Reading we improve user support and efficiency of interaction. The level of task engagement was inferred from the single-trial detectability of P300-related brain activity that was naturally evoked during interaction. With our approach no secondary task is needed to measure task load. It is based on research results on the single-stimulus paradigm, distribution of brain resources and its effect on the P300 event-related component. It further considers effects of the modulation caused by a delayed reaction time on the P300 component evoked by complex responses to task-relevant messages. We prove our concept using single-trial based machine learning analysis, analysis of averaged event-related potentials and behavioral analysis. As main results we show (1) a significant improvement of runtime needed to perform the interaction tasks compared to a setting in which all subjects could easily perform the tasks. We show that (2) the single-trial detectability of the event-related potential P300 can be used to measure the changes in task load and task engagement during complex interaction while also being sensitive to the level of experience of the operator and (3) can be used to adapt the MMI individually to the different needs of users without increasing total workload. Our online adaptation of the proposed MMI is based on a continuous supervision of the operator's cognitive resources by means of embedded Brain Reading. Operators with different qualifications or capabilities receive only as many tasks as they can perform to avoid mental

  14. An Intelligent Man-Machine Interface-Multi-Robot Control Adapted for Task Engagement Based on Single-Trial Detectability of P300.

    PubMed

    Kirchner, Elsa A; Kim, Su K; Tabie, Marc; Wöhrle, Hendrik; Maurus, Michael; Kirchner, Frank

    2016-01-01

    Advanced man-machine interfaces (MMIs) are being developed for teleoperating robots at remote and hardly accessible places. Such MMIs make use of a virtual environment and can therefore make the operator immerse him-/herself into the environment of the robot. In this paper, we present our developed MMI for multi-robot control. Our MMI can adapt to changes in task load and task engagement online. Applying our approach of embedded Brain Reading we improve user support and efficiency of interaction. The level of task engagement was inferred from the single-trial detectability of P300-related brain activity that was naturally evoked during interaction. With our approach no secondary task is needed to measure task load. It is based on research results on the single-stimulus paradigm, distribution of brain resources and its effect on the P300 event-related component. It further considers effects of the modulation caused by a delayed reaction time on the P300 component evoked by complex responses to task-relevant messages. We prove our concept using single-trial based machine learning analysis, analysis of averaged event-related potentials and behavioral analysis. As main results we show (1) a significant improvement of runtime needed to perform the interaction tasks compared to a setting in which all subjects could easily perform the tasks. We show that (2) the single-trial detectability of the event-related potential P300 can be used to measure the changes in task load and task engagement during complex interaction while also being sensitive to the level of experience of the operator and (3) can be used to adapt the MMI individually to the different needs of users without increasing total workload. Our online adaptation of the proposed MMI is based on a continuous supervision of the operator's cognitive resources by means of embedded Brain Reading. Operators with different qualifications or capabilities receive only as many tasks as they can perform to avoid mental

  15. Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram

    NASA Astrophysics Data System (ADS)

    Duan, Xiaopin; Xiao, Jisheng; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Mao, Shirui; Li, Yaping

    2014-03-01

    Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.

  16. Design, synthesis, and biological evaluation of benzoselenazole-stilbene hybrids as multi-target-directed anti-cancer agents.

    PubMed

    Yan, Jun; Guo, Yueyan; Wang, Yali; Mao, Fei; Huang, Ling; Li, Xingshu

    2015-05-01

    To identify novel multi-target-directed drug candidates for the treatment of cancer, a series of benzoselenazole-stilbene hybrids were synthesised by combining the pharmacophores of resveratrol and ebselen. The biological assay indicated that all of the hybrids exhibited antiproliferative activities against four human cancer cell lines and demonstrated good TrxR inhibitory activities. The mechanism of cell apoptosis was investigated in G2/M cell cycle arrest induced by compound 6e and the apoptosis of the human liver carcinoma Bel-7402 cell line. The significant increase in intracellular ROS confirmed that compound 6e was capable of causing oxidative stress-induced apoptosis in cancer cells. Our results support the potential of compound 6e as a candidate for further studies examining the development of novel drugs for cancer treatment. PMID:25817772

  17. Classification of compounds with distinct or overlapping multi-target activities and diverse molecular mechanisms using emerging chemical patterns.

    PubMed

    Namasivayam, Vigneshwaran; Hu, Ye; Balfer, Jenny; Bajorath, Jürgen

    2013-06-24

    The emerging chemical patterns (ECP) approach has been introduced for compound classification. Thus far, only very few ECP applications have been reported. Here, we further investigate the ECP methodology by studying complex classification problems. The analysis involves multi-target data sets with systematically organized subsets of compounds having distinct or overlapping target activities and, in addition, data sets containing classes of specifically active compounds with different mechanism-of-action. In systematic classification trials focusing on individual compound subsets or mechanistic classes, ECP calculations utilizing numerical descriptors achieve moderate to high sensitivity, dependent on the data set, and consistently high specificity. Accurate ECP predictions are already obtained on the basis of very small learning sets with only three positive training instances, which distinguishes the ECP approach from many other machine learning techniques. PMID:23692475

  18. Multi-target screening mines hesperidin as a multi-potent inhibitor: Implication in Alzheimer's disease therapeutics.

    PubMed

    Chakraborty, Sandipan; Bandyopadhyay, Jaya; Chakraborty, Sourav; Basu, Soumalee

    2016-10-01

    Alzheimer's disease (AD) is the most frequent form of neurodegenerative disorder in elderly people. Involvement of several pathogenic events and their interconnections make this disease a complex disorder. Therefore, designing compounds that can inhibit multiple toxic pathways is the most attractive therapeutic strategy in complex disorders like AD. Here, we have designed a multi-tier screening protocol combining ensemble docking to mine BACE1 inhibitor, as well as 2-D QSAR models for anti-amyloidogenic and antioxidant activities. An in house developed phytochemical library of 200 phytochemicals has been screened through this multi-target procedure which mine hesperidin, a flavanone glycoside commonly found in citrus food items, as a multi-potent phytochemical in AD therapeutics. Steady-state and time-resolved fluorescence spectroscopy reveal that binding of hesperidin to the active site of BACE1 induces a conformational transition of the protein from open to closed form. Hesperidin docks close to the catalytic aspartate residues and orients itself in a way that blocks the cavity opening thereby precluding substrate binding. Hesperidin is a high affinity BACE1 inhibitor and only 500 nM of the compound shows complete inhibition of the enzyme activity. Furthermore, ANS and Thioflavin-T binding assay show that hesperidin completely inhibits the amyloid fibril formation which is further supported by atomic force microscopy. Hesperidin exhibits moderate ABTS(+) radical scavenging assay but strong hydroxyl radical scavenging ability, as evident from DNA nicking assay. Present study demonstrates the applicability of a novel multi-target screening procedure to mine multi-potent agents from natural origin for AD therapeutics. PMID:27068363

  19. Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen.

    PubMed

    Luo, Zonghua; Sheng, Jianfei; Sun, Yang; Lu, Chuanjun; Yan, Jun; Liu, Anqiu; Luo, Hai-Bin; Huang, Ling; Li, Xingshu

    2013-11-27

    A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system. PMID:24160297

  20. Multi-target parallel processing approach for gene-to-structure determination of the influenza polymerase PB2 subunit.

    PubMed

    Armour, Brianna L; Barnes, Steve R; Moen, Spencer O; Smith, Eric; Raymond, Amy C; Fairman, James W; Stewart, Lance J; Staker, Bart L; Begley, Darren W; Edwards, Thomas E; Lorimer, Donald D

    2013-01-01

    Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year (1). Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans (2). Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains. PMID:23851357

  1. Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease

    PubMed Central

    Agis-Torres, Angel; Sölhuber, Monica; Fernandez, Maria; Sanchez-Montero, J.M.

    2014-01-01

    The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm “Multi-Target-Directed Ligands” (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches. PMID:24533013

  2. Ilizarov Treatment of Congenital Pseudarthrosis of the Tibia: A Multi-Targeted Approach Using the Ilizarov Technique

    PubMed Central

    Cho, Tae-Joon; Moon, Hyuk Ju

    2011-01-01

    Congenital pseudarthrosis of the tibia (CPT) is one of the most challenging problems in pediatric orthopaedics. The treatment goals are osteosynthesis, stabilization of the ankle mortise by fibular stabilization, and lower limb-length equalization. Each of these goals is difficult to accomplish but regardless of the surgical options, the basic biological considerations are the same: pseudarthrosis resection, biological bone bridging of the defect by stable fixation, and the correction of any angular deformity. The Ilizarov method is certainly valuable for the treatment of CPT because it can address not only pseudarthrosis but also all complex deformities associated with this condition. Leg-length discrepancy can be managed by proximal tibial lengthening using distraction osteogenesis combined with or without contralateral epiphysiodesis. However, treatment of CPT is fraught with complications due to the complex nature of the disease, and failure is common. Residual challenges, such as refracture, growth disturbance, and poor foot and ankle function with stiffness, are frequent and perplexing. Refracture is the most common and serious complication after primary healing and might result in the re-establishment of pseudarthrosis. Therefore, an effective, safe and practical treatment method that minimizes the residual challenges after healing and accomplishes the multiple goals of treatment is needed. This review describes a multi-targeted approach for tackling these challenges, which utilizes the Ilizarov technique in atrophic-type CPT. PMID:21369472

  3. Multi-Target Joint Detection and Estimation Error Bound for the Sensor with Clutter and Missed Detection

    PubMed Central

    Lian, Feng; Zhang, Guang-Hua; Duan, Zhan-Sheng; Han, Chong-Zhao

    2016-01-01

    The error bound is a typical measure of the limiting performance of all filters for the given sensor measurement setting. This is of practical importance in guiding the design and management of sensors to improve target tracking performance. Within the random finite set (RFS) framework, an error bound for joint detection and estimation (JDE) of multiple targets using a single sensor with clutter and missed detection is developed by using multi-Bernoulli or Poisson approximation to multi-target Bayes recursion. Here, JDE refers to jointly estimating the number and states of targets from a sequence of sensor measurements. In order to obtain the results of this paper, all detectors and estimators are restricted to maximum a posteriori (MAP) detectors and unbiased estimators, and the second-order optimal sub-pattern assignment (OSPA) distance is used to measure the error metric between the true and estimated state sets. The simulation results show that clutter density and detection probability have significant impact on the error bound, and the effectiveness of the proposed bound is verified by indicating the performance limitations of the single-sensor probability hypothesis density (PHD) and cardinalized PHD (CPHD) filters for various clutter densities and detection probabilities. PMID:26828499

  4. Multi-Target Joint Detection and Estimation Error Bound for the Sensor with Clutter and Missed Detection.

    PubMed

    Lian, Feng; Zhang, Guang-Hua; Duan, Zhan-Sheng; Han, Chong-Zhao

    2016-01-01

    The error bound is a typical measure of the limiting performance of all filters for the given sensor measurement setting. This is of practical importance in guiding the design and management of sensors to improve target tracking performance. Within the random finite set (RFS) framework, an error bound for joint detection and estimation (JDE) of multiple targets using a single sensor with clutter and missed detection is developed by using multi-Bernoulli or Poisson approximation to multi-target Bayes recursion. Here, JDE refers to jointly estimating the number and states of targets from a sequence of sensor measurements. In order to obtain the results of this paper, all detectors and estimators are restricted to maximum a posteriori (MAP) detectors and unbiased estimators, and the second-order optimal sub-pattern assignment (OSPA) distance is used to measure the error metric between the true and estimated state sets. The simulation results show that clutter density and detection probability have significant impact on the error bound, and the effectiveness of the proposed bound is verified by indicating the performance limitations of the single-sensor probability hypothesis density (PHD) and cardinalized PHD (CPHD) filters for various clutter densities and detection probabilities. PMID:26828499

  5. Multi-target Chromogenic Whole-mount In Situ Hybridization for Comparing Gene Expression Domains in Drosophila Embryos

    PubMed Central

    Hauptmann, Giselbert; Söll, Iris; Krautz, Robert; Theopold, Ulrich

    2016-01-01

    To analyze gene regulatory networks active during embryonic development and organogenesis it is essential to precisely define how the different genes are expressed in spatial relation to each other in situ. Multi-target chromogenic whole-mount in situ hybridization (MC-WISH) greatly facilitates the instant comparison of gene expression patterns, as it allows distinctive visualization of different mRNA species in contrasting colors in the same sample specimen. This provides the possibility to relate gene expression domains topographically to each other with high accuracy and to define unique and overlapping expression sites. In the presented protocol, we describe a MC-WISH procedure for comparing mRNA expression patterns of different genes in Drosophila embryos. Up to three RNA probes, each specific for another gene and labeled by a different hapten, are simultaneously hybridized to the embryo samples and subsequently detected by alkaline phosphatase-based colorimetric immunohistochemistry. The described procedure is detailed here for Drosophila, but works equally well with zebrafish embryos. PMID:26862978

  6. Nano-crystalline Ag-PbTe thermoelectric thin films by a multi-target PLD system

    NASA Astrophysics Data System (ADS)

    Cappelli, E.; Bellucci, A.; Medici, L.; Mezzi, A.; Kaciulis, S.; Fumagalli, F.; Di Fonzo, F.; Trucchi, D. M.

    2015-05-01

    It has been evaluated the ability of ArF pulsed laser ablation to grow nano-crystalline thin films of high temperature PbTe thermoelectric material, and to obtain a uniform and controlled Ag blending, through the entire thickness of the film, using a multi-target system in vacuum. The substrate used was a mirror polished technical alumina slab. The increasing atomic percentage of Ag effect on physical-chemical and electronic properties was evaluated in the range 300-575 K. The stoichiometry and the distribution of the Ag component, over the whole thickness of the samples deposited, have been studied by XPS (X-ray photoelectron spectroscopy) and corresponding depth profiles. The crystallographic structure of the film was analyzed by grazing incidence X-ray diffraction (GI-XRD) system. Scherrer analysis for crystallite size shows the presence of nano-structures, of the order of 30-35 nm. Electrical resistivity of the samples, studied by the four point probe method, as a function of increasing Ag content, shows a typical semi-conductor behavior. From conductivity values, carrier concentration and Seebeck parameter determination, the power factor of deposited films was calculated. Both XPS, Hall mobility and Seebeck analysis seem to indicate a limit value to the Ag solubility of the order of 5%, for thin films of ∼200 nm thickness, deposited at 350 °C. These data resulted to be comparable to theoretical evaluation for thin films but order of magnitude lower than the corresponding bulk materials.

  7. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    PubMed

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com . PMID:27167132

  8. Structural Mechanisms Determining Inhibition of the Collagen Receptor DDR1 by Selective and Multi-Targeted Type II Kinase Inhibitors

    PubMed Central

    Canning, Peter; Tan, Li; Chu, Kiki; Lee, Sam W.; Gray, Nathanael S.; Bullock, Alex N.

    2014-01-01

    The discoidin domain receptors (DDRs), DDR1 and DDR2, form a unique subfamily of receptor tyrosine kinases that are activated by the binding of triple-helical collagen. Excessive signaling by DDR1 and DDR2 has been linked to the progression of various human diseases, including fibrosis, atherosclerosis and cancer. We report the inhibition of these unusual receptor tyrosine kinases by the multi-targeted cancer drugs imatinib and ponatinib, as well as the selective type II inhibitor DDR1-IN-1. Ponatinib is identified as the more potent molecule, which inhibits DDR1 and DDR2 with an IC50 of 9 nM. Co-crystal structures of human DDR1 reveal a DFG-out conformation (DFG, Asp-Phe-Gly) of the kinase domain that is stabilized by an unusual salt bridge between the activation loop and αD helix. Differences to Abelson kinase (ABL) are observed in the DDR1 P-loop, where a β-hairpin replaces the cage-like structure of ABL. P-loop residues in DDR1 that confer drug resistance in ABL are therefore accommodated outside the ATP pocket. Whereas imatinib and ponatinib bind potently to both the DDR and ABL kinases, the hydrophobic interactions of the ABL P-loop appear poorly satisfied by DDR1-IN-1 suggesting a structural basis for its DDR1 selectivity. Such inhibitors may have applications in clinical indications of DDR1 and DDR2 overexpression or mutation, including lung cancer. PMID:24768818

  9. Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

    PubMed Central

    Romero Durán, Francisco J.; Alonso, Nerea; Caamaño, Olga; García-Mera, Xerardo; Yañez, Matilde; Prado-Prado, Francisco J.; González-Díaz, Humberto

    2014-01-01

    In a multi-target complex network, the links (Lij) represent the interactions between the drug (di) and the target (tj), characterized by different experimental measures (Ki, Km, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (cj). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally. PMID:25255029

  10. Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy.

    PubMed

    Noori-Daloii, Mohammad R; Momeny, Majid; Yousefi, Mehdi; Shirazi, Forough Golsaz; Yaseri, Mehdi; Motamed, Nasrin; Kazemialiakbar, Nazanin; Hashemi, Saeed

    2011-12-01

    The aim of the present study is to evaluate the effects of quercetin, a dietary flavonoid, on human prostate adenocarcinoma PC-3 cells. Lactate dehydrogenase (LDH) release, microculture tetrazolium test (MTT assay) and real-time PCR array were employed to evaluate the effects of quercetin on cell cytotoxicity, cell proliferation and expression of various genes in PC-3 cell line. Quercetin inhibited cell proliferation and modulated the expression of genes involved in DNA repair, matrix degradation and tumor invasion, angiogenesis, apoptosis, cell cycle, metabolism and glycolysis. No cytotoxicity of quercetin on PC-3 cells was observed. Taken together, as shown by the issues of the current study, the manifold inhibitory effects of quercetin on PC-3 cells may introduce quercetin as an efficacious anticancer agent in order to be used in the future nutritional transcriptomic investigations and multi-target therapy to overcome the therapeutic impediments against prostate cancer. PMID:20596804

  11. A Multi-Target Approach toward the Development of Novel Candidates for Antidermatophytic Activity: Ultrastructural Evidence on α-Bisabolol-Treated Microsporum gypseum.

    PubMed

    Romagnoli, Carlo; Baldisserotto, Anna; Malisardi, Gemma; Vicentini, Chiara B; Mares, Donatella; Andreotti, Elisa; Vertuani, Silvia; Manfredini, Stefano

    2015-01-01

    Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. α-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by α-bisabolol by TEM. PMID:26132903

  12. Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases.

    PubMed

    Hédou, Damien; Godeau, Julien; Loaëc, Nadège; Meijer, Laurent; Fruit, Corinne; Besson, Thierry

    2016-01-01

    A library of thirty novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives belonging to four series designated as 12, 13, 14 and 15 was efficiently prepared, helped by microwave-assisted technology when required. The efficient multistep synthesis of methyl 6-amino-2-cyano- benzo[d]thiazole-7-carboxylate (1) has been reinvestigated and performed on a multigram scale. The inhibitory potency of the final products against five kinases involved in Alzheimer's disease was evaluated. This study demonstrates that some molecules of the 12 and 13 series described in this paper are particularly promising for the development of new multi-target inhibitors of kinases. PMID:27144552

  13. Adaptive heterogeneous multi-robot teams

    SciTech Connect

    Parker, L.E.

    1998-11-01

    This research addresses the problem of achieving fault tolerant cooperation within small- to medium-sized teams of heterogeneous mobile robots. The author describes a novel behavior-based, fully distributed architecture, called ALLIANCE, that utilizes adaptive action selection to achieve fault tolerant cooperative control in robot missions involving loosely coupled, largely independent tasks. The robots in this architecture possess a variety of high-level functions that they can perform during a mission, and must at all times select an appropriate action based on the requirements of the mission, the activities of other robots, the current environmental conditions, and their own internal states. Since such cooperative teams often work in dynamic and unpredictable environments, the software architecture allows the team members to respond robustly and reliably to unexpected environmental changes and modifications in the robot team that may occur due to mechanical failure, the learning of new skills, or the addition or removal of robots from the team by human intervention. After presenting ALLIANCE, the author describes in detail the experimental results of an implementation of this architecture on a team of physical mobile robots performing a cooperative box pushing demonstration. These experiments illustrate the ability of ALLIANCE to achieve adaptive, fault-tolerant cooperative control amidst dynamic changes in the capabilities of the robot team.

  14. Prolonged-acting, Multi-targeting Gallium Nanoparticles Potently Inhibit Growth of Both HIV and Mycobacteria in Co-Infected Human Macrophages

    PubMed Central

    Narayanasamy, Prabagaran; Switzer, Barbara L.; Britigan, Bradley E.

    2015-01-01

    Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, macrophage and dendritic cell). Therefore, we hypothesized that one way this can be achieved is through drug-targeting by a nanoformulated drug that ideally would be active against both HIV and TB. Accordingly, we validated macrophage targeted long acting (sustained drug release) gallium (Ga) nanoformulation against HIV-mycobacterium co-infection. The multi-targeted Ga nanoparticle agent inhibited growth of both HIV and TB in the macrophage. The Ga nanoparticles reduced the growth of mycobacterium and HIV for up to 15 days following single drug loading. These results provide a potential new approach to treat HIV-TB co-infection that could eventually lead to improved clinical outcomes. PMID:25744727

  15. Multi-target determination of organic ultraviolet absorbents in organism tissues by ultrasonic assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Peng, Xianzhi; Jin, Jiabin; Wang, Chunwei; Ou, Weihui; Tang, Caiming

    2015-03-01

    A sensitive and reliable method was developed for multi-target determination of 13 most widely used organic ultraviolet (UV) absorbents (including UV filters and UV stabilizers) in aquatic organism tissues. The organic UV absorbents were extracted using ultrasonic-assisted extraction, purified via gel permeation chromatography coupled with silica gel column chromatography, and determined by ultra-high performance liquid chromatography-tandem mass spectrometry. Recoveries of the UV absorbents from organism tissues mostly ranged from 70% to 120% from fish filet with satisfactory reproducibility. Method quantification limits were 0.003-1.0ngg(-1) dry weight (dw) except for 2-ethylhexyl 4-methoxycinnamate. This method has been applied to analysis of the UV absorbents in wild and farmed aquatic organisms collected from the Pearl River Estuary, South China. 2-Hydroxy-4-methoxybenzophenone and UV-P were frequently detected in both wild and farmed marine organisms at low ngg(-1)dw. 3-(4-Methylbenzylidene)camphor and most of the benzotriazole UV stabilizers were also frequently detected in maricultured fish. Octocrylene and 2-ethylhexyl 4-methoxycinnamate were not detected in any sample. This work lays basis for in-depth study about bioaccumulation and biomagnification of the UV absorbents in marine environment. PMID:25637008

  16. Network pharmacology-based prediction of the multi-target capabilities of the compounds in Taohong Siwu decoction, and their application in osteoarthritis

    PubMed Central

    ZHENG, CHUN-SONG; XU, XIAO-JIE; YE, HONG-ZHI; WU, GUANG-WEN; LI, XI-HAI; XU, HUI-FENG; LIU, XIAN-XIANG

    2013-01-01

    Taohong Siwu decoction (THSWD), a formulation prescribed in traditional Chinese medicine (TCM), has been widely used in the treatment of osteoarthritis (OA). TCM has the potential to prevent diseases, such as OA, in an integrative and holistic manner. However, the system-level characterization of the drug-target interactions of THSWD has not been elucidated. In the present study, we constructed a novel modeling system, by integrating chemical space, virtual screening and network pharmacology, to investigate the molecular mechanism of action of THSWD. The chemical distribution of the ligand database and the potential compound prediction demonstrated that THSWD, as a natural combinatorial chemical library, comprises abundant drug-like and lead-like compounds that may act as potential inhibitors for a number of important target proteins associated with OA. Moreover, the results of the ‘compound-target network’ analysis demonstrated that 19 compounds within THSWD were correlated with more than one target, whilst the maximum degree of correlation for the compounds was seven. Furthermore, the ‘target-disease network’ indicated that THSWD may potentially be effective against 69 diseases. These results may aid in the understanding of the use of THSWD as a multi-target therapy in OA. Moreover, they may be useful in establishing other pharmacological effects that may be brought about by THSWD. The in silico method used in this study has the potential to advance the understanding of the molecular mechanisms of TCM. PMID:23935733

  17. Dovitinib (TKI258), a multi-target angiokinase inhibitor, is effective regardless of KRAS or BRAF mutation status in colorectal cancer

    PubMed Central

    Lee, Choong-Kun; Lee, Myung Eun; Lee, Won Suk; Kim, Jeong Min; Park, Kyu Hyun; Kim, Tae Soo; Lee, Kang Young; Ahn, Joong Bae; Chung, Hyun Cheol; Rha, Sun Young

    2015-01-01

    Introduction: We aimed to determine whether KRAS and BRAF mutant colorectal cancer (CRC) cells exhibit distinct sensitivities to the multi-target angiokinase inhibitor, TKI258 (dovitinib). Materials and methods: We screened 10 CRC cell lines by using receptor tyrosine kinase (RTK) array to identify activated RTKs. MTT assays, anchorage-independent colony-formation assays, and immunoblotting assays were performed to evaluate the in vitro anti-tumor effects of TKI258. In vivo efficacy study followed by pharmacodynamic evaluation was done. Results: Fibroblast Growth Factor Receptor 1 (FGFR1) and FGFR3 were among the most highly activated RTKs in CRC cell lines. In in vitro assays, the BRAF mutant HT-29 cells were more resistant to the TKI258 than the KRAS mutant LoVo cells. However, in xenograft assays, TKI258 equally delayed the growth of tumors induced by both cell lines. TUNEL assays showed that the apoptotic index was unchanged following TKI258 treatment, but staining for Ki-67 and CD31 was substantially reduced in both xenografts, implying an anti-angiogenic effect of the drug. TKI258 treatment was effective in delaying CRC tumor growth in vivo regardless of the KRAS and BRAF mutation status. Conclusions: Our results identify FGFRs as potential targets in CRC treatment and suggest that combined targeting of multiple RTKs with TKI258 might serve as a novel approach to improve outcome of patients with CRC. PMID:25628921

  18. Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease.

    PubMed

    Xie, Sai-Sai; Lan, Jin-Shuai; Wang, Xiaobing; Wang, Zhi-Min; Jiang, Neng; Li, Fan; Wu, Jia-Jia; Wang, Jin; Kong, Ling-Yi

    2016-04-01

    Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87μM and 0.93μM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37μM for hAChE; 1.98μM for hBuChE; 2.62μM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. PMID:26917219

  19. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease

    PubMed Central

    Tarozzi, Andrea; Bartolini, Manuela; Piazzi, Lorna; Valgimigli, Luca; Amorati, Riccardo; Bolondi, Cecilia; Djemil, Alice; Mancini, Francesca; Andrisano, Vincenza; Rampa, Angela

    2014-01-01

    The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer's disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Aβ42 self-aggregation, Aβ42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease. PMID:25505579

  20. Analytic Performance Prediction of Track-to-Track Association with Biased Data in Multi-Sensor Multi-Target Tracking Scenarios

    PubMed Central

    Tian, Wei; Wang, Yue; Shan, Xiuming; Yang, Jian

    2013-01-01

    An analytic method for predicting the performance of track-to-track association (TTTA) with biased data in multi-sensor multi-target tracking scenarios is proposed in this paper. The proposed method extends the existing results of the bias-free situation by accounting for the impact of sensor biases. Since little insight of the intrinsic relationship between scenario parameters and the performance of TTTA can be obtained by numerical simulations, the proposed analytic approach is a potential substitute for the costly Monte Carlo simulation method. Analytic expressions are developed for the global nearest neighbor (GNN) association algorithm in terms of correct association probability. The translational biases of sensors are incorporated in the expressions, which provide good insight into how the TTTA performance is affected by sensor biases, as well as other scenario parameters, including the target spatial density, the extraneous track density and the average association uncertainty error. To show the validity of the analytic predictions, we compare them with the simulation results, and the analytic predictions agree reasonably well with the simulations in a large range of normally anticipated scenario parameters. PMID:24036583

  1. Analytic performance prediction of track-to-track association with biased data in multi-sensor multi-target tracking scenarios.

    PubMed

    Tian, Wei; Wang, Yue; Shan, Xiuming; Yang, Jian

    2013-01-01

    An analytic method for predicting the performance of track-to-track association (TTTA) with biased data in multi-sensor multi-target tracking scenarios is proposed in this paper. The proposed method extends the existing results of the bias-free situation by accounting for the impact of sensor biases. Since little insight of the intrinsic relationship between scenario parameters and the performance of TTTA can be obtained by numerical simulations, the proposed analytic approach is a potential substitute for the costly Monte Carlo simulation method. Analytic expressions are developed for the global nearest neighbor (GNN) association algorithm in terms of correct association probability. The translational biases of sensors are incorporated in the expressions, which provide good insight into how the TTTA performance is affected by sensor biases, as well as other scenario parameters, including the target spatial density, the extraneous track density and the average association uncertainty error. To show the validity of the analytic predictions, we compare them with the simulation results, and the analytic predictions agree reasonably well with the simulations in a large range of normally anticipated scenario parameters. PMID:24036583

  2. Design and synthesis of 2-oxindole based multi-targeted inhibitors of PDK1/Akt signaling pathway for the treatment of glioblastoma multiforme.

    PubMed

    Sestito, Simona; Nesi, Giulia; Daniele, Simona; Martelli, Alma; Digiacomo, Maria; Borghini, Alice; Pietra, Daniele; Calderone, Vincenzo; Lapucci, Annalina; Falasca, Marco; Parrella, Paola; Notarangelo, Angelantonio; Breschi, Maria C; Macchia, Marco; Martini, Claudia; Rapposelli, Simona

    2015-11-13

    Aggressive behavior and diffuse infiltrative growth are the main features of Glioblastoma multiforme (GBM), together with the high degree of resistance and recurrence. Evidence indicate that GBM-derived stem cells (GSCs), endowed with unlimited proliferative potential, play a critical role in tumor development and maintenance. Among the many signaling pathways involved in maintaining GSC stemness, tumorigenic potential, and anti-apoptotic properties, the PDK1/Akt pathway is a challenging target to develop new potential agents able to affect GBM resistance to chemotherapy. In an effort to find new PDK1/Akt inhibitors, we rationally designed and synthesized a small family of 2-oxindole derivatives. Among them, compound 3 inhibited PDK1 kinase and downstream effectors such as CHK1, GS3Kα and GS3Kβ, which contribute to GCS survival. Compound 3 appeared to be a good tool for studying the role of the PDK1/Akt pathway in GCS self-renewal and tumorigenicity, and might represent the starting point for the development of more potent and focused multi-target therapies for GBM. PMID:26498573

  3. Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases.

    PubMed

    Sayre, P H; Finer-Moore, J S; Fritz, T A; Biermann, D; Gates, S B; MacKellar, W C; Patel, V F; Stroud, R M

    2001-11-01

    Crystal structures of four pyrrolo(2,3-d)pyrimidine-based antifolate compounds, developed as inhibitors of thymidylate synthase (TS) in a strategy to circumvent drug-resistance, have been determined in complexes with their in vivo target, human thymidylate synthase, and with the structurally best-characterized Escherichia coli enzyme, to resolutions of 2.2-3.0 A. The 2.9 A crystal structure of a complex of human TS with one of the inhibitors, the multi-targeted antifolate LY231514, demonstrates that this compound induces a "closed" enzyme conformation and leads to formation of a covalent bond between enzyme and substrate. This structure is one of the first liganded human TS structures, and its solution was aided by mutation to facilitate crystallization. Structures of three other pyrrolo(2,3-d)pyrimidine-based antifolates in complex with Escherichia coli TS confirm the orientation of this class of inhibitors in the active site. Specific interactions between the polyglutamyl moiety and a positively charged groove on the enzyme surface explain the marked increase in affinity of the pyrrolo(2,3-d)pyrimidine inhibitors once they are polyglutamylated, as mediated in vivo by the cellular enzyme folyl polyglutamate synthetase. PMID:11697906

  4. Self-assembled phenylalanine-α,β-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor.

    PubMed

    Panda, Jiban J; Yandrapu, Sarath; Kadam, Rajendra S; Chauhan, Virander S; Kompella, Uday B

    2013-12-28

    Current standard of care for sustained back of the eye drug delivery is surgical placement or injection of large, slow release implants using a relatively large 22 gauge needle. We designed novel dipeptide (phenylalanine-α,β-dehydrophenylalanine; Phe-∆Phe) based nanotubes with a diameter of ~15-30 nm and a length of ~1500 nm that could be injected with a 33 gauge needle for sustained intravitreal delivery of pazopanib, a multi-targeted tyrosine kinase inhibitor. The drug could be loaded during nanotube assembly or post-loaded after nanotube formation, with the former being more efficient at 25% w/w pazopanib loading and ~55% loading efficiency. Plain and peptide loaded nanotube were non-cytotoxic to retinal pigment epithelial cells even at a concentration of 200 μg/ml. Following intravitreal injection of fluorescently labeled nanotubes using a 33 gauge needle in a rat model, the nanotube persistence and drug delivery were monitored using noninvasive fluorophotometry, electron microscopy and mass spectrometry analysis. Nanotubes persisted in the vitreous humor during the 15 days study and pazopanib levels in the vitreous humor, retina, and choroid-RPE at the end of the study were 4.5, 5, and 2.5-folds higher, respectively, compared to the plain drug. Thus, Phe-∆Phe nanotubes allow intravitreal injections with a small gauge needle and sustain drug delivery. PMID:24075925

  5. Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer's disease based on the fusion of donepezil and melatonin.

    PubMed

    Wang, Jin; Wang, Zhi-Min; Li, Xue-Mei; Li, Fan; Wu, Jia-Jia; Kong, Ling-Yi; Wang, Xiao-Bing

    2016-09-15

    A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and β-amyloid (Aβ) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50 value of 193nM for eeAChE and 273nM for hAChE), strong inhibition of BuChE (IC50 value of 73nM for eqBuChE and 56nM for hBuChE), moderate inhibition of Aβ aggregation (56.3% at 20μM) and good antioxidant activity (3.28trolox equivalent by ORAC assay). Molecular modeling studies in combination with kinetic analysis revealed that 4u was a mixed-type inhibitor, binding simultaneously to catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4u could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results strongly indicated the hybridization approach is an efficient strategy to identify novel scaffolds with desired bioactivities, and further optimization of 4u may be helpful to develop more potent lead compound for AD treatment. PMID:27460699

  6. [Multi-Target Recognition of Internal and External Defects of Potato by Semi-Transmission Hyperspectral Imaging and Manifold Learning Algorithm].

    PubMed

    Huang, Tao; Li, Xiao-yu; Jin, Rui; Ku, Jing; Xu, Sen-miao; Xu, Meng-ling; Wu, Zhen-zhong; Kong, De-guo

    2015-04-01

    The present paper put forward a non-destructive detection method which combines semi-transmission hyperspectral imaging technology with manifold learning dimension reduction algorithm and least squares support vector machine (LSSVM) to recognize internal and external defects in potatoes simultaneously. Three hundred fifteen potatoes were bought in farmers market as research object, and semi-transmission hyperspectral image acquisition system was constructed to acquire the hyperspectral images of normal external defects (bud and green rind) and internal defect (hollow heart) potatoes. In order to conform to the actual production, defect part is randomly put right, side and back to the acquisition probe when the hyperspectral images of external defects potatoes are acquired. The average spectrums (390-1,040 nm) were extracted from the region of interests for spectral preprocessing. Then three kinds of manifold learning algorithm were respectively utilized to reduce the dimension of spectrum data, including supervised locally linear embedding (SLLE), locally linear embedding (LLE) and isometric mapping (ISOMAP), the low-dimensional data gotten by manifold learning algorithms is used as model input, Error Correcting Output Code (ECOC) and LSSVM were combined to develop the multi-target classification model. By comparing and analyzing results of the three models, we concluded that SLLE is the optimal manifold learning dimension reduction algorithm, and the SLLE-LSSVM model is determined to get the best recognition rate for recognizing internal and external defects potatoes. For test set data, the single recognition rate of normal, bud, green rind and hollow heart potato reached 96.83%, 86.96%, 86.96% and 95% respectively, and he hybrid recognition rate was 93.02%. The results indicate that combining the semi-transmission hyperspectral imaging technology with SLLE-LSSVM is a feasible qualitative analytical method which can simultaneously recognize the internal and

  7. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02).

    PubMed

    Iwamoto, Fabio M; Lamborn, Kathleen R; Robins, H Ian; Mehta, Minesh P; Chang, Susan M; Butowski, Nicholas A; Deangelis, Lisa M; Abrey, Lauren E; Zhang, Wei-Ting; Prados, Michael D; Fine, Howard A

    2010-08-01

    The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor receptor-alpha and -beta, and c-Kit, in recurrent glioblastoma. Patients with < or =2 relapses and no prior anti-VEGF/VEGFR therapy were treated with pazopanib 800 mg daily on 4-week cycles without planned interruptions. Brain magnetic resonance imaging and clinical reassessment were made every 8 weeks. The primary endpoint was efficacy as measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients with a median age of 53 years and median Karnofsky performance scale of 90 were accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. Two patients had a partial radiographic response by standard bidimensional measurements, whereas 9 patients (6 at the 8-week point and 3 only within the first month of treatment) had decreased contrast enhancement, vasogenic edema, and mass effect but <50% reduction in tumor. The median PFS was 12 weeks (95% confidence interval [CI]: 8-14 weeks) and only 1 patient had a PFS time > or =6 months (PFS6 = 3%). Thirty patients (86%) had died and median survival was 35 weeks (95% CI: 24-47 weeks). Pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381. PMID:20200024

  8. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02)

    PubMed Central

    Iwamoto, Fabio M.; Lamborn, Kathleen R.; Robins, H. Ian; Mehta, Minesh P.; Chang, Susan M.; Butowski, Nicholas A.; DeAngelis, Lisa M.; Abrey, Lauren E.; Zhang, Wei-Ting; Prados, Michael D.; Fine, Howard A.

    2010-01-01

    The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor receptor-α and -β, and c-Kit, in recurrent glioblastoma. Patients with ≤2 relapses and no prior anti-VEGF/VEGFR therapy were treated with pazopanib 800 mg daily on 4-week cycles without planned interruptions. Brain magnetic resonance imaging and clinical reassessment were made every 8 weeks. The primary endpoint was efficacy as measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients with a median age of 53 years and median Karnofsky performance scale of 90 were accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. Two patients had a partial radiographic response by standard bidimensional measurements, whereas 9 patients (6 at the 8-week point and 3 only within the first month of treatment) had decreased contrast enhancement, vasogenic edema, and mass effect but <50% reduction in tumor. The median PFS was 12 weeks (95% confidence interval [CI]: 8–14 weeks) and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). Thirty patients (86%) had died and median survival was 35 weeks (95% CI: 24–47 weeks). Pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381. PMID:20200024

  9. Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

    PubMed Central

    Zhang, Yaxiong; Kang, Shiyang; Fang, Wenfeng; Qin, Tao; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    Background Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis. Methods Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted. Results Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, P = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, P = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, P = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies. Conclusions This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology. PMID:25329056

  10. A modeling study for structure features of β-N-acetyl-D-hexosaminidase from Ostrinia furnacalis and its novel inhibitor allosamidin: species selectivity and multi-target characteristics.

    PubMed

    Wang, Yanli; Liu, Tian; Yang, Qing; Li, Zhong; Qian, Xuhong

    2012-04-01

    Insect β-N-acetyl-D-hexosaminidase, a chitin degrading enzyme, is physiologically important during the unique life cycle of the insect. OfHex1, a β-N-acetyl-D-hexosaminidase from the insect, Ostrinia furna, which was obtained by our laboratory (Gen Bank No.: ABI81756.1), was studied by molecular modeling as well as by molecular docking with its inhibitor, allosamidin. 3D model of OfHex1 was built through the ligand-supported homology modeling approach. The binding modes of its substrate and inhibitor were proposed through docking and cluster analysis. The pocket's size and shape of OfHex1 differ from that of human β-N-acetyl-D-hexosaminidase, which determined that allosamidin can selectively inhibit OfHex1 instead of human β-N-acetyl-D-hexosaminidase. Moreover, the multi-target characteristics of allosamidin that inhibit enzymes from different families, OfHex1 (EC 3.2.1.52; GH20) and chitinase (EC 3.2.1.14; GH18), were compared. The common -1/+1 sugar-binding site of chitinase and OfHex1, and the -2/-3 sugar-binding site in chitinase contribute to the binding of allosamidin. This work, at molecular level, proved that OfHex1 could be a potential species-specific target for novel green pesticide design and also provide the possibility to develop allosamidin or its derivatives as a new type of insecticide to 'hit two birds with one stone', which maybe become a novel strategy in pest control. PMID:22177554

  11. Anti-myeloma activity of a multi targeted kinase inhibitor, AT9283, via potent Aurora Kinase and STAT3 inhibition either alone or in combination with lenalidomide

    PubMed Central

    Santo, Loredana; Hideshima, Teru; Cirstea, Diana; Bandi, Madhavi; Nelson, Erik A.; Gorgun, Gullu; Rodig, Scott; Vallet, Sonia; Pozzi, Samantha; Patel, Kishan; Unitt, Christine; Squires, Matt; Hu, Yiguo; Chauhan, Dharminder; Mahindra, Anuj; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur

    2014-01-01

    Purpose Aurora Kinases, whose expression is linked to genetic instability and cellular proliferation, are under investigation as novel therapeutic targets in multiple myeloma (MM). Here, we investigated the preclinical activity of a small molecule–multi-targeted kinase inhibitor, AT9283, with potent activity against Aurora kinase A (AURKA), Aurora kinase B (AURKB) and Janus Kinase 2/3. Experimental design We evaluated the in vitro anti myeloma activity of AT9283 alone and in combination with lenalidomide and the in vivo efficacy by using a Xenograft mouse model of human MM. Results Our data demonstrated AT9283 induced cell growth inhibition and apoptosis in MM. Studying the apoptosis mechanism of AT9283 in MM, we observed features consistent with both AURKA and AURKB inhibition, e.g increase of cells with polyploid DNA content, decrease in phospho-Histone H3, and decrease of phospho-Aurora A. Importantly, AT9283 also inhibited STAT3 tyrosine phosphorylation in MM cells. Genetic depletion of STAT3, AURKA or AURKB showed growth inhibition of MM cells, suggesting a role of AT9283-induced inhibition of these molecules in the underlying mechanism of MM cell death. In vivo studies demonstrated decreased MM cell growth and prolonged survival in AT9283-treated mice compared to controls. Importantly, combination studies of AT9283 with lenalidomide showed significant synergistic cytotoxicity in MM cells, even in the presence of bone marrow stromal cells (BMSCs). Enhanced cytotoxicity was associated with increased inhibition of pSTAT3 and pERK. Conclusions Demonstration of in vitro and in vivo anti-MM activity of AT9283 provides the rationale for the clinical evaluation of AT9283 as monotherapy and in combination in patients with MM. PMID:21430070

  12. A Network Pharmacology Study of Chinese Medicine QiShenYiQi to Reveal Its Underlying Multi-Compound, Multi-Target, Multi-Pathway Mode of Action

    PubMed Central

    Li, Xiang; Wu, Leihong; Liu, Wei; Jin, Yecheng; Chen, Qian; Wang, Linli; Fan, Xiaohui; Li, Zheng; Cheng, Yiyu

    2014-01-01

    Chinese medicine is a complex system guided by traditional Chinese medicine (TCM) theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA) are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ), on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang). Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD)-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction. PMID:24817581

  13. Multi-Target QSAR Approaches for Modeling Protein Inhibitors. Simultaneous Prediction of Activities Against Biomacromolecules Present in Gram-Negative Bacteria.

    PubMed

    Speck-Planche, Alejandro; Cordeiro, M N D S

    2015-01-01

    Drug discovery is aimed at finding therapeutic agents for the treatment of many diverse diseases and infections. However, this is a very slow an expensive process, and for this reason, in silico approaches are needed to rationalize the search for new molecular entities with desired biological profiles. Models focused on quantitative structure-activity relationships (QSAR) have constituted useful complementary tools in medicinal chemistry, allowing the virtual predictions of dissimilar pharmacological activities of compounds. In the last 10 years, multi-target (mt) QSAR models have been reported, representing great advances with respect to those models generated from classical approaches. Thus, mt- QSAR models can simultaneously predict activities against different biological targets (proteins, microorganisms, cell lines, etc.) by using large and heterogeneous datasets of chemicals. The present review is devoted to discuss the most promising mt-QSAR models, particularly those developed for the prediction of protein inhibitors. We also report the first multi-tasking QSAR (mtk-QSAR) model for simultaneous prediction of inhibitors against biomacromolecules (specifically proteins) present in Gram-negative bacteria. This model allowed us to consider both different proteins and multiple experimental conditions under which the inhibitory activities of the chemicals were determined. The mtk-QSAR model exhibited accuracies higher than 98% in both training and prediction sets, also displaying a very good performance in the classification of active and inactive cases that depended on the specific elements of the experimental conditions. The physicochemical interpretations of the molecular descriptors were also analyzed, providing important insights regarding the molecular patterns associated with the appearance/enhancement of the inhibitory potency. PMID:25961517

  14. A preliminary trial using multi-target polymerase chain reaction (multiplex PCR) and restriction fragment length polymorphism (PCR-RFLP) on the same feedstuffs to detect tissues of animal origin.

    PubMed

    Colombo, F; Marchisio, E; Trezzi, I E; Peri, V; Pinotti, L; Baldi, A; Soncini, G

    2004-08-01

    A preliminary study using multi-target polymerase chain reaction (multiplex PCR) and restriction fragment length polymorphism (PCR-RFLP) was done on the same feedstuffs to detect animal tissues. The results of the two methods differ somewhat: PCR-RFLP did not detect any signal in any sample, but multiplex PCR detected a signal in one sample. These findings could be a basis for further investigations. PMID:15509020

  15. CRISPR MultiTargeter: A Web Tool to Find Common and Unique CRISPR Single Guide RNA Targets in a Set of Similar Sequences

    PubMed Central

    Prykhozhij, Sergey V.; Rajan, Vinothkumar; Gaston, Daniel; Berman, Jason N.

    2015-01-01

    Genome engineering has been revolutionized by the discovery of clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR-associated system genes (Cas) in bacteria. The type IIB Streptococcus pyogenes CRISPR/Cas9 system functions in many species and additional types of CRISPR/Cas systems are under development. In the type II system, expression of CRISPR single guide RNA (sgRNA) targeting a defined sequence and Cas9 generates a sequence-specific nuclease inducing small deletions or insertions. Moreover, knock-in of large DNA inserts has been shown at the sites targeted by sgRNAs and Cas9. Several tools are available for designing sgRNAs that target unique locations in the genome. However, the ability to find sgRNA targets common to several similar sequences or, by contrast, unique to each of these sequences, would also be advantageous. To provide such a tool for several types of CRISPR/Cas system and many species, we developed the CRISPR MultiTargeter software. Similar DNA sequences in question are duplicated genes and sets of exons of different transcripts of a gene. Thus, we implemented a basic sgRNA target search of input sequences for single-sgRNA and two-sgRNA/Cas9 nickase targeting, as well as common and unique sgRNA target searches in 1) a set of input sequences; 2) a set of similar genes or transcripts; or 3) transcripts a single gene. We demonstrate potential uses of the program by identifying unique isoform-specific sgRNA sites in 71% of zebrafish alternative transcripts and common sgRNA target sites in approximately 40% of zebrafish duplicated gene pairs. The design of unique targets in alternative exons is helpful because it will facilitate functional genomic studies of transcript isoforms. Similarly, its application to duplicated genes may simplify multi-gene mutational targeting experiments. Overall, this program provides a unique interface that will enhance use of CRISPR/Cas technology. PMID:25742428

  16. New Multi-target Antagonists of α1A-, α1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure.

    PubMed

    Nascimento-Viana, Jéssica B; Carvalho, Aline R; Nasciutti, Luiz Eurico; Alcántara-Hernández, Rocío; Chagas-Silva, Fernanda; Souza, Pedro A R; Romeiro, Luiz Antonio S; García-Sáinz, J Adolfo; Noël, François; Silva, Claudia Lucia Martins

    2016-01-01

    Benign prostatic hyperplasia (BPH) is characterized by stromal cell proliferation and contraction of the periurethral smooth muscle, causing lower urinary tract symptoms. Current BPH treatment, based on monotherapy with α1A-adrenoceptor antagonists, is helpful for many patients, but insufficient for others, and recent reports suggest that stimulation of α1D-adrenoceptors and 5-hydroxytryptamine (serotonin) (5-HT)1A receptors contributes to cell proliferation. In this study, we investigated the potential of three N-phenylpiperazine derivatives (LDT3, LDT5, and LDT8) as multi-target antagonists of BPH-associated receptors. The affinity and efficacy of LDTs were estimated in isometric contraction and competition-binding assays using tissues (prostate and aorta) and brain membrane samples enriched in specific on- or off-target receptors. LDTs' potency was estimated in intracellular Ca(2+) elevation assays using cells overexpressing human α1-adrenoceptor subtypes. The antiproliferative effect of LDTs on prostate cells from BPH patients was evaluated by viable cell counting and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays. We also determined LDTs' effects on rat intraurethral and arterial pressure. LDT3 and LDT5 are potent antagonists of α1A-, α1D-adrenoceptors, and 5-HT1A receptors (Ki values in the nanomolar range), and fully inhibited phenylephrine- and 5-HT-induced proliferation of BPH cells. In vivo, LDT3 and LDT5 fully blocked the increase of intraurethral pressure (IUP) induced by phenylephrine at doses (ED50 of 0.15 and 0.09 μg.kg(-1), respectively) without effect on basal mean blood pressure. LDT3 and LDT5 are multi-target antagonists of key receptors in BPH, and are capable of triggering both prostate muscle relaxation and human hyperplastic prostate cell growth inhibition in vitro. Thus, LDT3 and LDT5 represent potential new lead compounds for BPH treatment. PMID:26493747

  17. QiShenYiQi Pills, a compound in Chinese medicine, protects against pressure overload-induced cardiac hypertrophy through a multi-component and multi-target mode.

    PubMed

    Chen, Yuan-Yuan; Li, Quan; Pan, Chun-Shui; Yan, Li; Fan, Jing-Yu; He, Ke; Sun, Kai; Liu, Yu-Ying; Chen, Qing-Fang; Bai, Yan; Wang, Chuan-She; He, Bing; Lv, Ai-Ping; Han, Jing-Yan

    2015-01-01

    The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode. PMID:26136154

  18. QiShenYiQi Pills, a compound in Chinese medicine, protects against pressure overload-induced cardiac hypertrophy through a multi-component and multi-target mode

    PubMed Central

    Chen, Yuan-Yuan; Li, Quan; Pan, Chun-Shui; Yan, Li; Fan, Jing-Yu; He, Ke; Sun, Kai; Liu, Yu-Ying; Chen, Qing-Fang; Bai, Yan; Wang, Chuan-She; He, Bing; Lv, Ai-Ping; Han, Jing-Yan

    2015-01-01

    The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode. PMID:26136154

  19. Multi-Target Single Cycle Instrument Placement

    NASA Technical Reports Server (NTRS)

    Pedersen, Liam; Smith, David E.; Deans, Matthew; Sargent, Randy; Kunz, Clay; Lees, David; Rajagopalan, Srikanth; Bualat, Maria

    2005-01-01

    This presentation is about the robotic exploration of Mars using multiple targets command cycle, safe instrument placements, safe operation, and K9 Rover which has a 6 wheel steer rocket-bogey chassis (FIDO, MER), 70% MER size, 1.2 GHz Pentium M laptop running Linux OS, Odometry and compass/inclinometer, CLARAty architecture, 5 DOF manipulator w/CHAMP microscopic camera, SciCams, NavCams and HazCams.

  20. Particle separation

    DOEpatents

    Moosmuller, Hans; Chakrabarty, Rajan K.; Arnott, W. Patrick

    2011-04-26

    Embodiments of a method for selecting particles, such as based on their morphology, is disclosed. In a particular example, the particles are charged and acquire different amounts of charge, or have different charge distributions, based on their morphology. The particles are then sorted based on their flow properties. In a specific example, the particles are sorted using a differential mobility analyzer, which sorts particles, at least in part, based on their electrical mobility. Given a population of particles with similar electrical mobilities, the disclosed process can be used to sort particles based on the net charge carried by the particle, and thus, given the relationship between charge and morphology, separate the particles based on their morphology.

  1. Particle separation

    NASA Technical Reports Server (NTRS)

    Moosmuller, Hans (Inventor); Chakrabarty, Rajan K. (Inventor); Arnott, W. Patrick (Inventor)

    2011-01-01

    Embodiments of a method for selecting particles, such as based on their morphology, is disclosed. In a particular example, the particles are charged and acquire different amounts of charge, or have different charge distributions, based on their morphology. The particles are then sorted based on their flow properties. In a specific example, the particles are sorted using a differential mobility analyzer, which sorts particles, at least in part, based on their electrical mobility. Given a population of particles with similar electrical mobilities, the disclosed process can be used to sort particles based on the net charge carried by the particle, and thus, given the relationship between charge and morphology, separate the particles based on their morphology.

  2. "Dilute-and-inject" multi-target screening assay for highly polar doping agents using hydrophilic interaction liquid chromatography high resolution/high accuracy mass spectrometry for sports drug testing.

    PubMed

    Görgens, Christian; Guddat, Sven; Orlovius, Anne-Katrin; Sigmund, Gerd; Thomas, Andreas; Thevis, Mario; Schänzer, Wilhelm

    2015-07-01

    In the field of LC-MS, reversed phase liquid chromatography is the predominant method of choice for the separation of prohibited substances from various classes in sports drug testing. However, highly polar and charged compounds still represent a challenging task in liquid chromatography due to their difficult chromatographic behavior using reversed phase materials. A very promising approach for the separation of hydrophilic compounds is hydrophilic interaction liquid chromatography (HILIC). Despite its great potential and versatile advantages for the separation of highly polar compounds, HILIC is up to now not very common in doping analysis, although most manufacturers offer a variety of HILIC columns in their portfolio. In this study, a novel multi-target approach based on HILIC high resolution/high accuracy mass spectrometry is presented to screen for various polar stimulants, stimulant sulfo-conjugates, glycerol, AICAR, ethyl glucuronide, morphine-3-glucuronide, and myo-inositol trispyrophosphate after direct injection of diluted urine specimens. The usage of an effective online sample cleanup and a zwitterionic HILIC analytical column in combination with a new generation Hybrid Quadrupol-Orbitrap® mass spectrometer enabled the detection of highly polar analytes without any time-consuming hydrolysis or further purification steps, far below the required detection limits. The methodology was fully validated for qualitative and quantitative (AICAR, glycerol) purposes considering the parameters specificity; robustness (rRT < 2.0%); linearity (R > 0.99); intra- and inter-day precision at low, medium, and high concentration levels (CV < 20%); limit of detection (stimulants and stimulant sulfo-conjugates < 10 ng/mL; norfenefrine; octopamine < 30 ng/mL; AICAR < 10 ng/mL; glycerol 100 μg/mL; ETG < 100 ng/mL); accuracy (AICAR 103.8-105.5%, glycerol 85.1-98.3% at three concentration levels) and ion suppression/enhancement effects. PMID

  3. Immobilized magnetic beads based multi-target affinity selection coupled with high performance liquid chromatography-mass spectrometry for screening anti-diabetic compounds from a Chinese medicine "Tang-Zhi-Qing".

    PubMed

    Tao, Yi; Chen, Zhui; Zhang, Yufeng; Wang, Yi; Cheng, Yiyu

    2013-05-01

    We developed an approach for screening bioactive compounds from botanical drug using multiple target-immobilized magnetic beads coupled with high performance liquid chromatography-mass spectrometry. This novel approach was called magnetic beads based multi-target affinity selection-mass spectrometry (MT-ASMS). It can enrich and identify different types of ligands from mixture extracts. Multiple targets (maltase, invertase, lipase) were immobilized on the magnetic beads by covalent linkage using 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as reaction reagents, respectively. The properties of enzyme conjugated magnetic beads were characterized using transmission electron microscopy, X-ray diffractometer and vibration sample magnetometer. Several factors including pH, ion strength, incubation time and temperature were optimized using three known ligands (caffeic acid, ferulic acid, and hesperidin). The established MT-ASMS approach was applied to screening for ligands from a Chinese medicine "Tang-Zhi-Qing", which was used to treat type II diabetes in China. Seven bound compounds were identified via liquid chromatography-mass spectrometry (LC/MS). Five active compounds including 2,3,4,6-tetra-O-galloyl-D-glucose, 1,2,3,4-tetra-O-galloyl-D-glucose, 1,2,3,4,6-penta-O-galloyl-d-glucose, quercetin-3-O-β-D-glucuronide and quercetin-3-O-β-D-glucoside were identified and their activities were validated by conventional inhibitory assay. Our findings suggested that the proposed approach is efficient in screening compounds with multiple activities from extracts of botanical drugs. PMID:23501439

  4. ALLIANCE: An architecture for fault tolerant multi-robot cooperation

    SciTech Connect

    Parker, L.E.

    1995-02-01

    ALLIANCE is a software architecture that facilitates the fault tolerant cooperative control of teams of heterogeneous mobile robots performing missions composed of loosely coupled, largely independent subtasks. ALLIANCE allows teams of robots, each of which possesses a variety of high-level functions that it can perform during a mission, to individually select appropriate actions throughout the mission based on the requirements of the mission, the activities of other robots, the current environmental conditions, and the robot`s own internal states. ALLIANCE is a fully distributed, behavior-based architecture that incorporates the use of mathematically modeled motivations (such as impatience and acquiescence) within each robot to achieve adaptive action selection. Since cooperative robotic teams usually work in dynamic and unpredictable environments, this software architecture allows the robot team members to respond robustly, reliably, flexibly, and coherently to unexpected environmental changes and modifications in the robot team that may occur due to mechanical failure, the learning of new skills, or the addition or removal of robots from the team by human intervention. The feasibility of this architecture is demonstrated in an implementation on a team of mobile robots performing a laboratory version of hazardous waste cleanup.

  5. Cooperative Environment Scans Based on a Multi-Robot System

    PubMed Central

    Kwon, Ji-Wook

    2015-01-01

    This paper proposes a cooperative environment scan system (CESS) using multiple robots, where each robot has low-cost range finders and low processing power. To organize and maintain the CESS, a base robot monitors the positions of the child robots, controls them, and builds a map of the unknown environment, while the child robots with low performance range finders provide obstacle information. Even though each child robot provides approximated and limited information of the obstacles, CESS replaces the single LRF, which has a high cost, because much of the information is acquired and accumulated by a number of the child robots. Moreover, the proposed CESS extends the measurement boundaries and detects obstacles hidden behind others. To show the performance of the proposed system and compare this with the numerical models of the commercialized 2D and 3D laser scanners, simulation results are included. PMID:25789491

  6. ROBODEXS: multi-robot deployment and extraction system

    NASA Astrophysics Data System (ADS)

    Gray, Jeremy P.; Mason, James R.; Patterson, Michael S.; Skalny, Matthew W.

    2012-06-01

    The importance of Unmanned Ground Vehicles (UGV's) in the Military's operations is continually increasing. All Military branches now rely on advanced robotic technologies to aid in their missions' operations. The integration of these technologies has not only enhanced capabilities, but has increased personnel safety by generating larger standoff distances. Currently most UGV's are deployed by an exposed dismounted Warfighter because the Military possess a limited capability to do so remotely and can only deploy a single UGV. This paper explains the conceptual development of a novel approach to remotely deploy and extract multiple robots from a single host platform. The Robotic Deployment & Extraction System (ROBODEXS) is a result of our development research to improve marsupial robotic deployment at safe standoff distances. The presented solution is modular and scalable, having the ability to deploy anywhere from two to twenty robots from a single deployment mechanism. For larger carrier platforms, multiple sets of ROBODEXS modules may be integrated for deployment and extraction of even greater numbers of robots. Such a system allows mass deployment and extraction from a single manned/unmanned vehicle, which is not currently possible with other deployment systems.

  7. Locally oriented potential field for controlling multi-robots

    NASA Astrophysics Data System (ADS)

    Romero, Roseli A. F.; Prestes, Edson; Idiart, Marco A. P.; Faria, Gedson

    2012-12-01

    In this paper, we present an extension of the boundary value problem path planner (BVP PP) to control multiple robots in a robot soccer scenario. This extension is called Locally Oriented Potential Field (LOPF) and computes a potential field from the numerical solution of a BVP using local relaxations in different patches of the solution space. This permits that a single solution of the BVP endows distinct robots with different behaviors in a team. We present the steps to implement LOPF as well as several results obtained in simulation.

  8. Control fusion for safe multi-robot coordination

    NASA Astrophysics Data System (ADS)

    Bostelman, Roger; Marvel, Jeremy

    2014-05-01

    Future smart manufacturing systems will include more complex coordination of mobile manipulators (i.e., robot arms mounted on mobile bases). The National Institute of Standards and Technology (NIST) conducts research on the safety and performance of multiple collaborating robots using a mobile platform, an automatic guided vehicle (AGV) with an onboard manipulator. Safety standards for robots and industrial vehicles each mandate their failsafe control, but there is little overlap between the standards that can be relied on when the two systems are combined and their independent controllers make collaborative decisions for safe movement. This paper briefly discusses previously uncovered gaps between AGV and manipulator standards and details decision sharing for when manipulators and AGVs are combined into a collaborative, mobile manipulator system. Tests using the NIST mobile manipulator with various control methods were performed and are described along with test results and plans for further, more complex tests of implicit and explicit coordination control of the mobile manipulator.

  9. Particle generator

    DOEpatents

    Hess, Wayne P.; Joly, Alan G.; Gerrity, Daniel P.; Beck, Kenneth M.; Sushko, Peter V.; Shlyuger, Alexander L.

    2005-06-28

    Energy tunable solid state sources of neutral particles are described. In a disclosed embodiment, a halogen particle source includes a solid halide sample, a photon source positioned to deliver photons to a surface of the halide, and a collimating means positioned to accept a spatially defined plume of hyperthermal halogen particles emitted from the sample surface.

  10. Alpha Particle

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Term that is sometimes used to describe a helium nucleus, a positively charged particle that consists of two protons and two neutrons, bound together. Alpha particles, which were discovered by Ernest Rutherford (1871-1937) in 1898, are emitted by atomic nuclei that are undergoing alpha radioactivity. During this process, an unstable heavy nucleus spontaneously emits an alpha particle and transmut...

  11. Particle Detectors

    NASA Astrophysics Data System (ADS)

    Grupen, Claus; Shwartz, Boris

    2011-09-01

    Preface to the first edition; Preface to the second edition; Introduction; 1. Interactions of particles and radiation with matter; 2. Characteristic properties of detectors; 3. Units of radiation measurements and radiation sources; 4. Accelerators; 5. Main physical phenomena used for particle detection and basic counter types; 6. Historical track detectors; 7. Track detectors; 8. Calorimetry; 9. Particle identification; 10. Neutrino detectors; 11. Momentum measurement and muon detection; 12. Ageing and radiation effects; 13. Example of a general-purpose detector: Belle; 14. Electronics; 15. Data analysis; 16. Applications of particle detectors outside particle physics; 17. Glossary; 18. Solutions; 19. Resumé; Appendixes; Index.

  12. Discovery of LY2457546: a multi-targeted anti-angiogenic kinase inhibitor with a novel spectrum of activity and exquisite potency in the acute myelogenous leukemia-Flt-3-internal tandem duplication mutant human tumor xenograft model.

    PubMed

    Burkholder, Timothy P; Clayton, Joshua R; Rempala, Mark E; Henry, James R; Knobeloch, John M; Mendel, David; McLean, Johnathan A; Hao, Yan; Barda, David A; Considine, Eileen L; Uhlik, Mark T; Chen, Yuefeng; Ma, Liandong; Bloem, Laura J; Akunda, Jacqueline K; McCann, Denis J; Sanchez-Felix, Manuel; Clawson, David K; Lahn, Michael M; Starling, James J

    2012-06-01

    LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. With activities against both Tie2 and Eph receptors, LY2457546 possesses an activity profile that distinguishes it from multikinase inhibitors. When compared head to head with sunitinib, LY2457546 was more potent for inhibition of endothelial tube formation in an in vitro angiogenesis co-culture model with an intermittent treatment design. In vivo, LY2457546 inhibited VEGF-driven autophosphorylation of lung KDR in the mouse and rat in a dose and concentration dependent manner. LY2457546 was well tolerated and exhibited efficacy in a 13762 syngeneic rat mammary tumor model in both once and twice daily continuous dosing schedules and in mouse human tumor xenograft models of lung, colon, and prostate origin. Additionally, LY2457546 caused complete regression of well-established tumors in an acute myelogenous leukemia (AML) FLT3-ITD mutant xenograft tumor model. The observed efficacy that was displayed by LY2457546 in the AML FLT3-ITD mutant tumor model was superior to sunitinib when both were evaluated using equivalent doses normalized to in vivo inhibition of pKDR in mouse lung. LY2457546 was well tolerated in non-clinical toxicology studies conducted in rats and dogs. The majority of the toxicities observed were similar to those observed with other multi-targeted anti-angiogenic kinase inhibitors (MAKs) and included bone marrow hypocellularity, hair and skin depigmentation, cartilage dysplasia and lymphoid organ degeneration and necrosis. Thus, the unique spectrum of target activity, potent in vivo anti-tumor efficacy in a variety of rodent and human solid tumor models, exquisite potency against a clinically relevant model of AML, and non

  13. Particle astrophysics

    NASA Technical Reports Server (NTRS)

    Sadoulet, Bernard; Cronin, James; Aprile, Elena; Barish, Barry C.; Beier, Eugene W.; Brandenberger, Robert; Cabrera, Blas; Caldwell, David; Cassiday, George; Cline, David B.

    1991-01-01

    The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented.

  14. Particle therapy

    SciTech Connect

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  15. Particle astrophysics

    NASA Astrophysics Data System (ADS)

    Sadoulet, Bernard; Cronin, James; Aprile, Elena; Barish, Barry C.; Beier, Eugene W.; Brandenberger, Robert; Cabrera, Blas; Caldwell, David; Cassiday, George; Cline, David B.

    The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented.

  16. Magnetic particles

    NASA Technical Reports Server (NTRS)

    Chang, Manchium (Inventor); Colvin, Michael S. (Inventor)

    1989-01-01

    Magnetic polymer particles are formed by swelling porous, polymer particles and impregnating the particles with an aqueous solution of precursor magnetic metal salt such as an equimolar mixture of ferrous chloride and ferric chloride. On addition of a basic reagent such as dilute sodium hydroxide, the metal salts are converted to crystals of magnetite which are uniformly contained througout the pores of the polymer particle. The magnetite content can be increased and neutral buoyancy achieved by repetition of the impregnaton and neutralization steps to adjust the magnetite content to a desired level.

  17. Particle preconcentrator

    DOEpatents

    Linker, K.L.; Conrad, F.J.; Custer, C.A.; Rhykerd, C.L. Jr.

    1998-12-29

    An apparatus and method are disclosed for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents. 3 figs.

  18. Particle preconcentrator

    SciTech Connect

    Linker, K.L.; Conrad, F.J.; Custer, C.A.; Rhykerd, C.L. Jr

    2000-07-11

    An apparatus and method are disclosed for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a previous screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  19. Particle preconcentrator

    SciTech Connect

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    1998-01-01

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  20. Particle preconcentrator

    SciTech Connect

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    2005-09-20

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  1. Particle preconcentrator

    SciTech Connect

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    2000-01-01

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  2. Elementary particles

    NASA Astrophysics Data System (ADS)

    Fritzsch, Harald; Heusch, Karin

    Introduction -- Electrons and atomic nuclei -- Quantum properties of atoms and particles -- The knives of Democritus -- Quarks inside atomic nuclei -- Quantum electrodynamics -- Quantum chromodynamics -- Mesons, baryons, and quarks -- Electroweak interactions -- Grand unification -- Conclusion.

  3. Magnetic particles

    NASA Technical Reports Server (NTRS)

    Chang, Manchium (Inventor); Colvin, Michael S. (Inventor); Rembaum, Alan (Inventor); Richards, Gil F. (Inventor)

    1987-01-01

    Metal oxide containing polymers and particularly styrene, acrylic or protein polymers containing fine, magnetic iron oxide particles are formed by combining a NO.sub.2 -substituted polymer with an acid such as hydrochloric acid in the presence of metal, particularly iron particles. The iron is oxidized to fine, black Fe.sub.3 O.sub.4 particles which deposit selectively on the polymer particles. Nitrated polymers are formed by reacting functionally substituted, nitrated organic compounds such as trinitrobenzene sulfonate or dinitrofluoro benzene with a functionally coreactive polymer such as an amine modified acrylic polymer or a protein. Other transition metals such as cobalt can also be incorporated into polymers using this method.

  4. Elementary Particles

    ERIC Educational Resources Information Center

    Parham, R.

    1974-01-01

    Presents the text of a speech given to a conference of physics teachers in which the full spectrum of elementary particles is given, along with their classification. Also includes some teaching materials available on this topic. (PEB)

  5. A bio-inspired swarm robot coordination algorithm for multiple target searching

    NASA Astrophysics Data System (ADS)

    Meng, Yan; Gan, Jing; Desai, Sachi

    2008-04-01

    The coordination of a multi-robot system searching for multi targets is challenging under dynamic environment since the multi-robot system demands group coherence (agents need to have the incentive to work together faithfully) and group competence (agents need to know how to work together well). In our previous proposed bio-inspired coordination method, Local Interaction through Virtual Stigmergy (LIVS), one problem is the considerable randomness of the robot movement during coordination, which may lead to more power consumption and longer searching time. To address these issues, an adaptive LIVS (ALIVS) method is proposed in this paper, which not only considers the travel cost and target weight, but also predicting the target/robot ratio and potential robot redundancy with respect to the detected targets. Furthermore, a dynamic weight adjustment is also applied to improve the searching performance. This new method a truly distributed method where each robot makes its own decision based on its local sensing information and the information from its neighbors. Basically, each robot only communicates with its neighbors through a virtual stigmergy mechanism and makes its local movement decision based on a Particle Swarm Optimization (PSO) algorithm. The proposed ALIVS algorithm has been implemented on the embodied robot simulator, Player/Stage, in a searching target. The simulation results demonstrate the efficiency and robustness in a power-efficient manner with the real-world constraints.

  6. Auroral particles

    NASA Technical Reports Server (NTRS)

    Evans, David S.

    1987-01-01

    The problems concerning the aurora posed prior to the war are now either solved in principle or were restated in a more fundamental form. The pre-war hypothesis concerning the nature of the auroral particles and their energies was fully confirmed, with the exception that helium and oxygen ions were identified as participating in the auroral particle precipitation in addition to the protons. The nature of the near-Earth energization processes affecting auroral particles was clarified. Charged particle trajectories in various electric field geometries were modeled. The physical problems have now moved from determining the nature and geometry of the electric fields, which accelerate charged particles near the Earth, to accounting for the existence of these electric fields as a natural consequence of the solar wind's interaction with Earth. Ultimately the reward in continuing the work in auroral and magnetospheric particle dynamics will be a deeper understanding of the subtleties of classical electricity and magnetism as applied to situations not blessed with well-defined and invariant geometries.

  7. Particle Sizer

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Microspheres are tiny plastic beads that represent the first commercial products manufactured in orbit. An example of how they are used is a new aerodynamic particle sizer designated APS 33B produced by TSI Incorporated. TSI purchased the microspheres from the National Bureau of Standards which certified their exact size and the company uses them in calibration of the APS 33B* instrument, latest in a line of TSI systems for generating counting and weighing minute particles of submicron size. Instruments are used for evaluating air pollution control devices, quantifying environments, meteorological research, testing filters, inhalation, toxicology and other areas where generation or analysis of small airborne particles is required. * The APS 33B is no longer being manufactured. An improved version, APS 3320, is now being manufactured. 2/28/97

  8. Carbon particles

    DOEpatents

    Hunt, Arlon J.

    1984-01-01

    A method and apparatus whereby small carbon particles are made by pyrolysis of a mixture of acetylene carried in argon. The mixture is injected through a nozzle into a heated tube. A small amount of air is added to the mixture. In order to prevent carbon build-up at the nozzle, the nozzle tip is externally cooled. The tube is also elongated sufficiently to assure efficient pyrolysis at the desired flow rates. A key feature of the method is that the acetylene and argon, for example, are premixed in a dilute ratio, and such mixture is injected while cool to minimize the agglomeration of the particles, which produces carbon particles with desired optical properties for use as a solar radiant heat absorber.

  9. Particle filter-based track before detect algorithms

    NASA Astrophysics Data System (ADS)

    Boers, Yvo; Driessen, Hans

    2003-12-01

    In this paper we will give a general system setup, that allows the formulation of a wide range of Track Before Detect (TBD) problems. A general basic particle filter algorithm for this system is also provided. TBD is a technique, where tracks are produced directly on the basis of raw (radar) measurements, e.g. power or IQ data, without intermediate processing and decision making. The advantage over classical tracking is that the full information is integrated over time, this leads to a better detection and tracking performance, especially for weak targets. In this paper we look at the filtering and the detection aspect of TBD. We will formulate a detection result, that allows the user to implement any optimal detector in terms of the weights of a running particle filter. We will give a theoretical as well as a numerical (experimental) justification for this. Furthermore, we show that the TBD setup, that is chosen in this paper, allows a straightforward extension to the multi-target case. This easy extension is also due to the fact that the implementation of the solution is by means of a particle filter.

  10. Particle filter-based track before detect algorithms

    NASA Astrophysics Data System (ADS)

    Boers, Yvo; Driessen, Hans

    2004-01-01

    In this paper we will give a general system setup, that allows the formulation of a wide range of Track Before Detect (TBD) problems. A general basic particle filter algorithm for this system is also provided. TBD is a technique, where tracks are produced directly on the basis of raw (radar) measurements, e.g. power or IQ data, without intermediate processing and decision making. The advantage over classical tracking is that the full information is integrated over time, this leads to a better detection and tracking performance, especially for weak targets. In this paper we look at the filtering and the detection aspect of TBD. We will formulate a detection result, that allows the user to implement any optimal detector in terms of the weights of a running particle filter. We will give a theoretical as well as a numerical (experimental) justification for this. Furthermore, we show that the TBD setup, that is chosen in this paper, allows a straightforward extension to the multi-target case. This easy extension is also due to the fact that the implementation of the solution is by means of a particle filter.

  11. Particle blender

    DOEpatents

    Willey, Melvin G.

    1981-01-01

    An infinite blender that achieves a homogeneous mixture of fuel microspheres is provided. Blending is accomplished by directing respective groups of desired particles onto the apex of a stationary coaxial cone. The particles progress downward over the cone surface and deposit in a space at the base of the cone that is described by a flexible band provided with a wide portion traversing and in continuous contact with the circumference of the cone base and extending upwardly therefrom. The band, being attached to the cone at a narrow inner end thereof, causes the cone to rotate on its arbor when the band is subsequently pulled onto a take-up spool. As a point at the end of the wide portion of the band passes the point where it is tangent to the cone, the blended particles are released into a delivery tube leading directly into a mold, and a plate mounted on the lower portion of the cone and positioned between the end of the wide portion of the band and the cone assures release of the particles only at the tangent point.

  12. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  13. Particle astrophysics

    SciTech Connect

    Sadoulet, B. |

    1992-12-31

    In the last few years, particle astrophysics has emerged as a new field at the frontier between high energy astrophysics, cosmology, and particle physics. Two spectacular achievements of this new field in the last decade have been the establishment of neutrino astronomy with the detection of solar neutrinos by two independent experiments and the spectacular observation of the neutrinos from the supernova SN1987A. In addition, the field has produced tantalizing hints of new physics beyond the standard models of astrophysics and particle physics, generating enthusiastic attempts to confirm these potential effects. This new field involves some two hundred experimentalists and a similar number of theorists, most of them coming from particle and nuclear physics, and as scientist will see, their effort is to a large extent complementary to accelerator based high energy physics. This review attempts, at the beginning of this workshop, to capture the excitement of this new field. Summary talks will describe in more detail some of the topics discussed in the study groups.

  14. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  15. Particle Physics

    NASA Astrophysics Data System (ADS)

    Cooper, Necia Grant; West, Geoffrey B.

    1988-06-01

    Preface; Introduction; Part I. Theoretical Framework: 1. Scale and dimension - From animals to quarks Geoffrey B. West; 2. Particle physics and the standard model Stuart Raby, Richard C. Slansky and Geoffrey B. West; QCD on a Cray: the masses of elementary particles Gerald Guralnik, Tony Warnock and Charles Zemach; Lecture Notes - From simple field theories to the standard model; 3. Toward a unified theory: an essay on the role of supergravity in the search for unification Richard C. Slansky; 4. Supersymmetry at 100 GeV Stuart Raby; 5. The family problem T. Goldman and Michael Martin Nieto; Part II. Experimental Developments: 6. Experiments to test unification schemes Gary H. Sanders; 7. The march toward higher energies S. Peter Rosen; LAMPF II and the High-Intensity Frontier Henry A. Thiessen; The SSC - An engineering challenge Mahlon T. Wilson; 8. Science underground - the search for rare events L. M. Simmons, Jr; Part III. Personal Perspectives: 9. Quarks and quirks among friends Peter A. Carruthers, Stuart Raby, Richard C. Slansky, Geoffrey B. West and George Zweig; Index.

  16. Microfabricated particle focusing device

    DOEpatents

    Ravula, Surendra K.; Arrington, Christian L.; Sigman, Jennifer K.; Branch, Darren W.; Brener, Igal; Clem, Paul G.; James, Conrad D.; Hill, Martyn; Boltryk, Rosemary June

    2013-04-23

    A microfabricated particle focusing device comprises an acoustic portion to preconcentrate particles over large spatial dimensions into particle streams and a dielectrophoretic portion for finer particle focusing into single-file columns. The device can be used for high throughput assays for which it is necessary to isolate and investigate small bundles of particles and single particles.

  17. Particle Tracks in Aerogel

    NASA Technical Reports Server (NTRS)

    2005-01-01

    In an experiment using a special air gun, particles are shot into aerogel at high velocities. Closeup of particles that have been captured in aerogel are shown here. The particles leave a carrot-shaped trail in the aerogel. Aerogel was used on the Stardust spacecraft to capture comet particles from Comet Wild 2.

  18. Chemical Modification of the Multi-Target Neuroprotective Compound Fisetin

    PubMed Central

    Chiruta, Chandramouli; Schubert, David; Dargusch, Richard; Maher, Pamela

    2012-01-01

    Many factors are implicated in age-related CNS disorders making it unlikely that modulating only a single factor will provide effective treatment. Perhaps a better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Recently, we identified an orally active, neuroprotective and cognition-enhancing molecule, the flavonoid fisetin, that is effective in several animal models of CNS disorders. Fisetin has direct antioxidant activity and can also increase the intracellular levels of glutathione (GSH), the major endogenous antioxidant. In addition, fisetin has both neurotrophic and anti-inflammatory activity. However, its relatively high EC50 in cell based assays, low lipophilicity, high tPSA and poor bioavailability suggest that there is room for medicinal chemical improvement. Here we describe a multi-tiered approach to screening that has allowed us to identify fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model while at the same time maintaining other key activities. PMID:22192055

  19. Multi-Target Analysis and Design of Mitochondrial Metabolism

    PubMed Central

    Carapezza, Giovanni; Lió, Pietro; Nicosia, Giuseppe

    2015-01-01

    Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach specific optimal output values chosen by the researcher. In this work, we take into account a mitochondrial model analyzed with flux-balance analysis. The optimal design and assessment of these models is achieved through single- and/or multi-objective optimization techniques driven by epsilon-dominance and identifiability analysis. Our optimization algorithm searches for the values of the flux rates that optimize multiple cellular functions simultaneously. The optimization of the fluxes of the metabolic network includes not only input fluxes, but also internal fluxes. A faster convergence process with robust candidate solutions is permitted by a relaxed Pareto dominance, regulating the granularity of the approximation of the desired Pareto front. We find that the maximum ATP production is linked to a total consumption of NADH, and reaching the maximum amount of NADH leads to an increasing request of NADH from the external environment. Furthermore, the identifiability analysis characterizes the type and the stage of three monogenic diseases. Finally, we propose a new methodology to extend any constraint-based model using protein abundances. PMID:26376088

  20. Multi-target tracking using a hybrid joint transform correlator

    NASA Technical Reports Server (NTRS)

    Yu, Francis T. S.; Tam, Eddy C.; Tanone, Aris; Gregory, Don A.; Juday, Richard D.

    1990-01-01

    A technique using data association target tracking in a motion sequence via an adaptive joint transform correlator is presented. The massive data in the field of view can be reduced to a few correlation peaks. The average velocity of a target during the tracking cycle is then determined from the location of the correlation peak. A data-association algorithm is used for the analysis of these correlation signals, for which multiple targets can be tracked. A phase-mostly liquid-crystal TV is used in the hybrid joint transform correlation system, and simultaneous tracking of three targets is demonstrated.

  1. Laser particle sorter

    DOEpatents

    Martin, John C.; Buican, Tudor N.

    1989-01-01

    Method and apparatus for sorting particles, such as biological particles. A first laser defines an optical path having an intensity gradient which is effective to propel the particles along the path but which is sufficiently weak that the particles are not trapped in an axial direction. A probe laser beam interrogates the particles to identify predetermined phenotypical characteristics of the particles. A second laser beam intersects the driving first laser beam, wherein the second laser beam is activated by an output signal indicative of a predetermined characteristic. The second laser beam is switchable between a first intensity and a second intensity, where the first intensity is effective to displace selected particles from the driving laser beam and the second intensity is effective to propel selected particles along the deflection laser beam. The selected particles may then be propelled by the deflection beam to a location effective for further analysis.

  2. Laser particle sorter

    DOEpatents

    Martin, J.C.; Buican, T.N.

    1987-11-30

    Method and apparatus are provided for sorting particles, such as biological particles. A first laser is used to define an optical path having an intensity gradient which is effective to propel the particles along the path but which is sufficiently weak that the particles are not trapped in an axial direction. A probe laser beam is provided for interrogating the particles to identify predetermined phenotypical characteristics of the particles. A second laser beam is provided to intersect the driving first laser beam, wherein the second laser beam is activated by an output signal indicative of a predetermined characteristic. The second laser beam is switchable between a first intensity and a second intensity, where the first intensity is effective to displace selected particles from the driving laser beam and the second intensity is effective to propel selected particles along the deflection laser beam. The selected particles may then be propelled by the deflection beam to a location effective for further analysis. 2 figs.

  3. Particle capture device

    DOEpatents

    Jayne, John T.; Worsnop, Douglas R.

    2016-02-23

    In example embodiments, particle collection efficiency in aerosol analyzers and other particle measuring instruments is improved by a particle capture device that employs multiple collisions to decrease momentum of particles until the particles are collected (e.g., vaporized or come to rest). The particle collection device includes an aperture through which a focused particle beam enters. A collection enclosure is coupled to the aperture and has one or more internal surfaces against which particles of the focused beam collide. One or more features are employed in the collection enclosure to promote particles to collide multiple times within the enclosure, and thereby be vaporized or come to rest, rather than escape through the aperture.

  4. The Particle Hunters

    NASA Astrophysics Data System (ADS)

    Ne'eman, Yuval; Kirsh, Yoram

    1996-04-01

    Preface to the first edition; Preface to the second edition; 1. The building blocks of the atom; 2. Physical laws for small particles; 3. The discoveries of the 1930s and 1940s; 4. Particle accelerators - or from hunters to farmers; 5. Strange particles; 6. Basic forces and the classification of particles; 7. Conservation laws; 8. Short-lived particles; 9. To the quarks - via the eightfold way; 10. More quarks - or charm, truth and beauty; 11. The standard model and beyond; Appendix 1. Properties of semi-stable particles; Appendix 2. The Greek alphabet; Name index; Subject index.

  5. Particle exposures and infections

    EPA Science Inventory

    Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Ci...

  6. Solar Neutral Particles

    NASA Video Gallery

    This animation shows a neutral solar particle's path leaving the sun, following the magnetic field lines out to the heliosheath. The solar particle hits a hydrogen atom, stealing its electron, and ...

  7. Composite powder particles

    NASA Technical Reports Server (NTRS)

    Parker, Donald S. (Inventor); MacDowell, Louis G. (Inventor)

    2009-01-01

    A liquid coating composition including a coating vehicle and composite powder particles disposed within the coating vehicle. Each composite powder particle may include a magnesium component, a zinc component, and an indium component.

  8. Solar flare particle radiation

    NASA Technical Reports Server (NTRS)

    Lanzerotti, L. J.

    1972-01-01

    The characteristics of the solar particles accelerated by solar flares and subsequently observed near the orbit of the earth are studied. Considered are solar particle intensity-time profiles, the composition and spectra of solar flare events, and the propagation of solar particles in interplanetary space. The effects of solar particles at the earth, riometer observations of polar cap cosmic noise absorption events, and the production of solar cell damage at synchronous altitudes by solar protons are also discussed.

  9. Magnetospheric particle populations.

    NASA Technical Reports Server (NTRS)

    Vette, J. I.

    1972-01-01

    Significant results of magnetospheric charged particle measurements conducted within the past two years are reviewed in an attempt to provide a general description of relationships among particle populations in the magnetosheath, plasma sheet, extraterrestrial ring current region, electron trough, pseudotrapping region, and stable-trapping region. Special attention is given to the characteristics of protons, electrons, alpha particles, and particles with charge greater than three in the stable trapping region.

  10. Classical confined particles

    NASA Technical Reports Server (NTRS)

    Horzela, Andrzej; Kapuscik, Edward

    1993-01-01

    An alternative picture of classical many body mechanics is proposed. In this picture particles possess individual kinematics but are deprived from individual dynamics. Dynamics exists only for the many particle system as a whole. The theory is complete and allows to determine the trajectories of each particle. It is proposed to use our picture as a classical prototype for a realistic theory of confined particles.

  11. Anatomy of Particle Diffusion

    ERIC Educational Resources Information Center

    Bringuier, E.

    2009-01-01

    The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact…

  12. High energy particle astronomy.

    NASA Technical Reports Server (NTRS)

    Buffington, A.; Muller, R. A.; Smith, L. H.; Smoot, G. F.

    1972-01-01

    Discussion of techniques currently used in high energy particle astronomy for measuring charged and neutral cosmic rays and their isotope and momentum distribution. Derived from methods developed for accelerator experiments in particle physics, these techniques help perform important particle astronomy experiments pertaining to nuclear cosmic ray and gamma ray research, electron and position probes, and antimatter searches.

  13. Review of particle properties

    SciTech Connect

    Wohl; Cahn, R.N.; Rittenberg, A.; Trippe, T.G.; Yost, G.P.; Porter, F.; Hernandez, J.J.; Montanet, L.; Hendrick, R.E.; Crawford, R.L.

    1984-04-01

    This review of the properties of leptons, mesons, and baryons is an updating of the Review of Particle Properties, Particle Data Group (Phys. Lett. 111B (1982)). Data are evaluated, listed, averaged, and summarized in tables. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available.

  14. Atmospheric particle sampler

    NASA Technical Reports Server (NTRS)

    Miller, C. G.; Stephens, J. B.

    1976-01-01

    Positive and/or negative pressure is used to trap airborne particles against a filter. Positive pressure is provided by low molecular weight gas (He or H) to achieve high particle velocity and high capture percentage. Trapped particles are examined under electron microscope.

  15. When is a Particle?

    ERIC Educational Resources Information Center

    Drell, Sidney D.

    1978-01-01

    Gives a new definition for the concept of the elementary particle in nuclear physics. Explains why the existance of the quark as an elementary particle could be an accepted fact even though it lacks what traditionally identifies a particle. Compares this with the development which took place during the discovery of the neutrino in the early…

  16. Particle film technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Particle Film Technology involves establishing a mineral particle film on the surface of a plant or plant product that: (1) is chemically inert, (2) has a mean particle diameter < 2 um, (3) is formulated to spread and create a uniform film, (4) does not physically disrupt gas exchange from the le...

  17. Dust particle velocity measurement

    NASA Technical Reports Server (NTRS)

    Thielman, L. O.

    1976-01-01

    A laser Doppler velocimeter was used to measure the velocity distributions for particles entering a vacuum chamber from the atmosphere through calibrated leaks. The relative number of particles per velocity interval was obtained for particulates of three size distributions and two densities passing through six different leak geometries. The velocity range 15 to 320 meters per second was investigated. Peak particle velocities were found to occur in the 15 to 150 meters per second range depending upon type of particle and leak geometry. A small fraction of the particles were found to have velocities in the 150 to 320 meters per second range.

  18. Adhesive particle shielding

    DOEpatents

    Klebanoff, Leonard Elliott; Rader, Daniel John; Walton, Christopher; Folta, James

    2009-01-06

    An efficient device for capturing fast moving particles has an adhesive particle shield that includes (i) a mounting panel and (ii) a film that is attached to the mounting panel wherein the outer surface of the film has an adhesive coating disposed thereon to capture particles contacting the outer surface. The shield can be employed to maintain a substantially particle free environment such as in photolithographic systems having critical surfaces, such as wafers, masks, and optics and in the tools used to make these components, that are sensitive to particle contamination. The shield can be portable to be positioned in hard-to-reach areas of a photolithography machine. The adhesive particle shield can incorporate cooling means to attract particles via the thermophoresis effect.

  19. Fuzzy Logic Particle Tracking

    NASA Technical Reports Server (NTRS)

    2005-01-01

    A new all-electronic Particle Image Velocimetry technique that can efficiently map high speed gas flows has been developed in-house at the NASA Lewis Research Center. Particle Image Velocimetry is an optical technique for measuring the instantaneous two component velocity field across a planar region of a seeded flow field. A pulsed laser light sheet is used to illuminate the seed particles entrained in the flow field at two instances in time. One or more charged coupled device (CCD) cameras can be used to record the instantaneous positions of particles. Using the time between light sheet pulses and determining either the individual particle displacements or the average displacement of particles over a small subregion of the recorded image enables the calculation of the fluid velocity. Fuzzy logic minimizes the required operator intervention in identifying particles and computing velocity. Using two cameras that have the same view of the illumination plane yields two single exposure image frames. Two competing techniques that yield unambiguous velocity vector direction information have been widely used for reducing the single-exposure, multiple image frame data: (1) cross-correlation and (2) particle tracking. Correlation techniques yield averaged velocity estimates over subregions of the flow, whereas particle tracking techniques give individual particle velocity estimates. For the correlation technique, the correlation peak corresponding to the average displacement of particles across the subregion must be identified. Noise on the images and particle dropout result in misidentification of the true correlation peak. The subsequent velocity vector maps contain spurious vectors where the displacement peaks have been improperly identified. Typically these spurious vectors are replaced by a weighted average of the neighboring vectors, thereby decreasing the independence of the measurements. In this work, fuzzy logic techniques are used to determine the true

  20. Experiments with particle damping

    NASA Astrophysics Data System (ADS)

    Hollkamp, Joseph J.; Gordon, Robert W.

    1998-06-01

    High cycle fatigue in jet engines is a current military concern. The vibratory stresses that cause fatigue can be reduced by adding damping. However, the high temperatures that occur in the gas turbine greatly hinder the application of mature damping technologies. One technology which may perform in the harsh environment is particle damping. Particle damping involves placing metallic or ceramic particles inside structural cavities. As the cavity vibrates, energy is dissipated through particle collisions. Performance is influenced by many parameters including the type, shape, and size of the particles; the amount of free volume for the particles to move in; density of the particles; and the level of vibration. This paper presents results from a series of experiments designed to gain an appreciation of the important parameters. The experimental setup consists of a cantilever beam with drilled holes. These holes are partially filled with particles. The types of particles, location of the particles, fill level, and other parameters are varied. Damping is estimated for each configuration. Trends in the results are studied to determine the influence of the varied parameter.

  1. Precision gap particle separator

    DOEpatents

    Benett, William J.; Miles, Robin; Jones, II., Leslie M.; Stockton, Cheryl

    2004-06-08

    A system for separating particles entrained in a fluid includes a base with a first channel and a second channel. A precision gap connects the first channel and the second channel. The precision gap is of a size that allows small particles to pass from the first channel into the second channel and prevents large particles from the first channel into the second channel. A cover is positioned over the base unit, the first channel, the precision gap, and the second channel. An port directs the fluid containing the entrained particles into the first channel. An output port directs the large particles out of the first channel. A port connected to the second channel directs the small particles out of the second channel.

  2. CLASHING BEAM PARTICLE ACCELERATOR

    DOEpatents

    Burleigh, R.J.

    1961-04-11

    A charged-particle accelerator of the proton synchrotron class having means for simultaneously accelerating two separate contra-rotating particle beams within a single annular magnet structure is reported. The magnet provides two concentric circular field regions of opposite magnetic polarity with one field region being of slightly less diameter than the other. The accelerator includes a deflector means straddling the two particle orbits and acting to collide the two particle beams after each has been accelerated to a desired energy. The deflector has the further property of returning particles which do not undergo collision to the regular orbits whereby the particles recirculate with the possibility of colliding upon subsequent passages through the deflector.

  3. Methods for forming particles

    DOEpatents

    Fox, Robert V.; Zhang, Fengyan; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin

    2016-06-21

    Single source precursors or pre-copolymers of single source precursors are subjected to microwave radiation to form particles of a I-III-VI.sub.2 material. Such particles may be formed in a wurtzite phase and may be converted to a chalcopyrite phase by, for example, exposure to heat. The particles in the wurtzite phase may have a substantially hexagonal shape that enables stacking into ordered layers. The particles in the wurtzite phase may be mixed with particles in the chalcopyrite phase (i.e., chalcopyrite nanoparticles) that may fill voids within the ordered layers of the particles in the wurtzite phase thus produce films with good coverage. In some embodiments, the methods are used to form layers of semiconductor materials comprising a I-III-VI.sub.2 material. Devices such as, for example, thin-film solar cells may be fabricated using such methods.

  4. Particle formation and interaction

    NASA Technical Reports Server (NTRS)

    Squyres, Steven; Corso, George J.; Griffiths, Lynn D.; Mackinnon, Ian D. R.; Marshall, John R.; Nuth, Joseph A., III; Werner, Brad; Wolfe, John

    1987-01-01

    A wide variety of experiments can be conducted on the Space Station that involve the physics of small particles of planetary significance. Processes of interest include nucleation and condensation of particles from a gas, aggregation of small particles into larger ones, and low velocity collisions of particles. All of these processes could be investigated with a general purpose facility on the Space Station. The microgravity environment would be necessary to perform many experiments, as they generally require that particles be suspended for periods substantially longer than are practical at 1 g. Only experiments relevant to planetary processes will be discussed in detail here, but it is important to stress that a particle facility will be useful to a wide variety of scientific disciplines, and can be used to address many scientific problems.

  5. Particle Swarm Optimization

    NASA Technical Reports Server (NTRS)

    Venter, Gerhard; Sobieszczanski-Sobieski Jaroslaw

    2002-01-01

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

  6. The Sisyphus particle detector

    NASA Technical Reports Server (NTRS)

    Soberman, R. K.

    1974-01-01

    The particle measurement subsystem planned for the MJS 77 mission is described. Scientific objectives with respect to Saturn's rings are as follows: (1) measure particles outside the visible rings, including particulates orbiting in more distant rings and particles scattered out of visible rings, (2) measure meteoroid environment in vicinity of Saturn, and (3) develop an understanding of the dynamics of the rings with respect to their collisional interaction with the environment.

  7. Polarization of intersecting particles

    NASA Astrophysics Data System (ADS)

    Paley, A. V.; Radchik, A. V.; Smith, G. B.; Vagov, A. V.

    1994-06-01

    An exact expression for the polarizability of intersecting circular cylinders has been derived covering all degrees of intersection and arbitrary complex dielectric constants for the particle material. This enables a comparison between the induced dipole moment on two particles of almost identical shape; a cardioid and a particular pair of overlapping cylinders. The absorption spectra in the small particle limit are extremely sensitive to the detailed shape of the surfaces near the point of intersection.

  8. Restoring particle phenomenology

    NASA Astrophysics Data System (ADS)

    Valente, Giovanni

    2015-08-01

    No-go theorems are known in the literature to the effect that, in relativistic quantum field theory, particle localizability in the strict sense violates relativistic causality. In order to account for particle phenomenology without particle ontology, Halvorson and Clifton (2002) proposed an approximate localization scheme. In a recent paper, Arageorgis and Stergiou (2013) proved a no-go result that suggests that, even within such a scheme, there would arise act-outcome correlations over the entire spacetime, thereby violating relativistic causality. Here, we show that this conclusion is untenable. In particular, we argue that one can recover particle phenomenology without having to give up relativistic causality.

  9. Bioactivation of particles

    DOEpatents

    Pinaud, Fabien; King, David; Weiss, Shimon

    2011-08-16

    Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

  10. Dielectrophoretic particle-particle interaction under AC electrohydrodynamic flow conditions.

    PubMed

    Lee, Doh-Hyoung; Yu, Chengjie; Papazoglou, Elisabeth; Farouk, Bakhtier; Noh, Hongseok M

    2011-09-01

    We used the Maxwell stress tensor method to understand dielectrophoretic particle-particle interactions and applied the results to the interpretation of particle behaviors under alternating current (AC) electrohydrodynamic conditions such as AC electroosmosis (ACEO) and electrothermal flow (ETF). Distinct particle behaviors were observed under ACEO and ETF. Diverse particle-particle interactions observed in experiments such as particle clustering, particles keeping a certain distance from each other, chain and disc formation and their rotation, are explained based on the numerical simulation data. The improved understanding of particle behaviors in AC electrohydrodynamic flows presented here will enable researchers to design better particle manipulation strategies for lab-on-a-chip applications. PMID:21823132