Science.gov

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. Semi-Autonomous Collaborative Control of Multi-Robotic Systems for Multi-Task Multi-Target Pairing

    DTIC Science & Technology

    2011-11-01

    this paper proposes a control method for a single- master multi-slave ( SMMS ) teleoperator to cooperatively con- trol a team of mobile robots for a multi... SMMS ) teleoperator to cooperatively control a team of mobile robots for a multi-target mission. The major components of the proposed control method...required human resources and amplifying the human effort, the single-master multi-slave ( SMMS ) teleoperation has been con- sidered in this paper. Fong et

  3. Distributed Multi Robot Simultaneous Localization and Mapping with Consensus Particle Filtering

    NASA Astrophysics Data System (ADS)

    Hidayat, F.; Trilaksono, B. R.; Hindersah, H.

    2017-01-01

    These paper present distributed computations of join probabilities SLAM with consensus particle filtering algorithm. We consider groups of robot observe an unknown environment and build the global maps. In this paper, every local map is a global map. Global maps build by using its own information and the information obtained from the other robots. We use particles likelihood as transfer parameters. The information can be transferred to other robot if reach global agreement on particles weight. The global agreement can be obtained by using the Consensus Particle Filtering algorithm, computation is done locally on each robot. After reaching an agreement, then the global map can be built and information of the global map is owned on each robot.

  4. Heterogeneous Multi-Robot Cooperation

    DTIC Science & Technology

    1994-02-01

    Approaches to Multi-Robot Cooperative Control ................ 196 8.2.1 " Swarm " Cooperation ....... ...................... 196 8.2.2 "Intentional...involves the study of emergent cooperation in colonies, or swarms , of robots - an approach comparable to differentiating animal societies. This...using intention- ally cooperating robots to guide the activities of smaller groups of swarm robots in a coordinated way. The research presented in this

  5. Multi-robot control interface

    DOEpatents

    Bruemmer, David J [Idaho Falls, ID; Walton, Miles C [Idaho Falls, ID

    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.

  6. Multi-Robot Systems in Military Domains (Les Systemes Multi-Robots Dans les Domaines Militaires)

    DTIC Science & Technology

    2008-12-01

    Interaction with Multi-Robot Systems David Kortenkamp, Debra Schreckenghost, and Cheryl Martin Human-Robot Interactions in Robot-Assisted Urban Search...RTO-TR-IST-032 On Dynamic Reconfiguration of Multi-Robot Formations Rafael Fierro , Aveek K. Das Distributed Multi-Robot Mapping Dieter Fox...Robot Testbed for Biologically-Inspired Cooperative Control Rafael Fierro , Justin Clark, Dean Hougen, and Sesh Commuri Part VI – Human-Robot Interaction

  7. INL Multi-Robot Control Interface

    SciTech Connect

    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.

  8. Effects of Agent Transparency on Multi-Robot Management Effectiveness

    DTIC Science & Technology

    2015-09-01

    ARL-TR-7466 ● SEP 2015 US Army Research Laboratory Effects of Agent Transparency on Multi- Robot Management Effectiveness by...SEP 2015 US Army Research Laboratory Effects of Agent Transparency on Multi- Robot Management Effectiveness by Joseph E Mercado Oak...Final 3. DATES COVERED (From - To) October 2013–September 2014 4. TITLE AND SUBTITLE Effects of Agent Transparency on Multi- Robot Management

  9. 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.

  10. Design and Evaluation of a Multi-Robot Control Interface

    DTIC Science & Technology

    2003-10-01

    Baur “Multi-Robot Remote Driving with Collaborative Control”, in Proc. of the IEEE International Workshop on Robot and Human Communication , Bordeaux...International Workshop on Robot and Human Communication , Bordeaux, Paris, France 2001.

  11. Guaranteeing Spoof-Resilient Multi-Robot Networks

    DTIC Science & Technology

    2016-02-12

    Noname manuscript No. (will be inserted by the editor) Guaranteeing Spoof-Resilient Multi- Robot Networks Stephanie Gil †1 · Swarun Kumar †2 · Mark...Mazumder 3 · Dina Katabi 1 · Daniela Rus 1 December 14, 2015 Abstract Multi- robot networks use wireless communica- tion to provide wide-ranging services...such as aerial surveil- lance and unmanned delivery. However, effective coordina- tion between multiple robots requires trust, making them

  12. 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.

  13. Adaptive Division of Labor in Large-Scale Minimalist Multi-Robot Systems

    DTIC Science & Technology

    2003-01-01

    Matarić. A general, local algorithm for robot formations. IEEE Transactions on Robotics and Automation, Special Issue on Multi- Robot Systems, 18(5):837...Matarić. Sold!: Auction meth- ods for multi-robot coordination. IEEE Transactions on Robotics and Automation, Special Issue on Multi- Robot Systems...Alliance: An architecture for fault tolerant multi-robot cooperation. IEEE Transactions on Robotics and Automation, 14(2):220–240, 1998. [15] G

  14. Probabilistic Verification of Multi-Robot Missions in Uncertain Environments

    DTIC Science & Technology

    2015-11-01

    Probabilistic Verification of Multi- Robot Missions in Uncertain Environments Damian M. Lyons*, Ronald C. Arkin‡, Shu Jiang‡, Dagan Harrington...Abstract— The effective use of autonomous robot teams in highly-critical missions depends on being able to establish performance guarantees...However, establishing a guarantee for the behavior of an autonomous robot operating in an uncertain environment with obstacles is a challenging problem

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

    PubMed

    Liu, Zhe; Wang, Zulin; Xu, Mai

    2016-05-09

    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.

  16. 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.

  17. Research status of multi - robot systems task allocation and uncertainty treatment

    NASA Astrophysics Data System (ADS)

    Li, Dahui; Fan, Qi; Dai, Xuefeng

    2017-08-01

    The multi-robot coordination algorithm has become a hot research topic in the field of robotics in recent years. It has a wide range of applications and good application prospects. This paper analyzes and summarizes the current research status of multi-robot coordination algorithms at home and abroad. From task allocation and dealing with uncertainty, this paper discusses the multi-robot coordination algorithm and presents the advantages and disadvantages of each method commonly used.

  18. Review of multi-robot taxonomy, trends, and applications for defense and space

    NASA Astrophysics Data System (ADS)

    Lucas, Nathan P.; Pandya, Abhilash K.; Ellis, R. Darin

    2012-06-01

    Multi-robot systems may be capable of performing a wide variety of distributed, hazardous, and complex tasks that are difficult or impossible for independent robots. Despite significant research accomplishments and potential benefits for defense, space, and other application areas, much of the technology is still in early development. This paper reviews influential taxonomy and trends in multi-robotics. A condensed model of multi-robot interaction is presented. Potential near-term defense and space applications are categorized into two mission types: distributed and complex. Conclusions are drawn concerning research opportunities toward multi-robot systems for the defense and space domains.

  19. 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.

  20. Stochastic Model-Based Control of Multi-Robot Systems

    DTIC Science & Technology

    2009-06-30

    dual [6]. For example, we use the optimal control theory to derive linear quadratic regulator ( LQR ), and in the same theoretical framework we can derive...a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...Final Technical Report 23-09-2008 - 22-06-2009 Stochastic Model-Based Control of Multi-Robot Systems W911NF-08-1-0503 Dejan Milutinovic and Devendra P

  1. Research status of operational environment partitioning and path planning for multi - robot systems

    NASA Astrophysics Data System (ADS)

    Dai, Xuefeng; Fan, Qi; Li, Dahui

    2017-08-01

    There is a lot of applications for multi-robot systems instead of single robot systems. Therefore, coordination algorithms have become popular in the field of robotics for two decades. This paper analyzes and summarizes the current research status of coordinated algorithms for multi-robot systems, from perspectives of partitioning the environment, and path planning.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. SMC-PHD-based multi-target tracking with reduced peak extraction

    NASA Astrophysics Data System (ADS)

    Dunne, Darcy; Tharmarasa, Ratnasingham; Lang, Thomas; Kirubarajan, T.

    2009-08-01

    The Probability Hypothesis Density (PHD) filter is a powerful new tool in the field of multitarget tracking. Unlike classical multi-target tracking approaches, such as Multiple Hypothesis Tracking (MHT), in each scan it provides a complete solution to multi-target state estimation without the necessity for explicit measurement-to-track data association. The PHD filter recursively propagates the first order moment of the multi-target posterior. This allows us to determine the expected number of targets as well as their state estimates at each scan. However, there is no implicit connection between the target state estimates in consecutive scans. In this paper, a new cluster-based approach is proposed for track labeling in the Sequential Monte Carlo (SMC i.e. particle filter based) PHD filter. The method associates a likelihood vector to each particle in the SMC estimate. This vector indicates the likelihood that the particle estimate belongs to each of the established target tracks. This likelihood vector is propagated along with the PHD moment and updated with the PHD function. By maintaining a set of associations from scan to scan, the new method provides a complete PHD solution for a multi-target tracking application over time. The method is tested on both clean and noisy multi-target tracking scenarios and the results are compared to some previously published methods.

  7. Online Mapping and Perception Algorithms for Multi-robot Teams Operating in Urban Environments

    DTIC Science & Technology

    2015-01-01

    Online mapping and perception algorithms for multi-robot teams operating in urban environments by Johannes H. Strom A dissertation submitted in...REPORT DATE 2015 2. REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Online Mapping and Perception Algorithms for...SUPPLEMENTARY NOTES 14. ABSTRACT This thesis investigates some of the sensing and perception challenges faced by multi-robot teams equipped with

  8. The Control Based on Internal Average Kinetic Energy in Complex Environment for Multi-robot System

    NASA Astrophysics Data System (ADS)

    Yang, Mao; Tian, Yantao; Yin, Xianghua

    In this paper, reference trajectory is designed according to minimum energy consumed for multi-robot system, which nonlinear programming and cubic spline interpolation are adopted. The control strategy is composed of two levels, which lower-level is simple PD control and the upper-level is based on the internal average kinetic energy for multi-robot system in the complex environment with velocity damping. Simulation tests verify the effectiveness of this control strategy.

  9. Temporal clustering in the multi-target tracking environment

    NASA Astrophysics Data System (ADS)

    Kelso, Thomas S.

    1988-08-01

    In multi-target tracking problems such as those found in high-energy particle physics, fluid mechanics, and ballistic missile defense, the common objective is to separate the data into observations associated with individual targets and to use this data to estimate the targets' trajectories. In defense related applications, it is necessary to have algorithms which are computationally efficient, robust, and minimize data storage requirements. Recently developed approaches in the field of multi-target tracking, however, have been shown to have significant computational disadvantages. In this study, non-hierarchical clustering methods are combined with computationally efficient algorithms such as those used to solve assignment and quadratic programming problems to provide an integrated procedure which is computationally efficient, minimizes data storage requirements, and gives a reasonable estimate of the number of targets. Combined with a sequential estimation filter such as the extended Kalman filter, the procedure can provide estimates of a target's state and state covariance after three observations and continuously maintain updated target state estimates in real time. Empirical results based on 100 targets in ballistic trajectories have demonstrated this method's effectiveness by properly clustering data with four measurement attributes (range, range rate, azimuth, and elevation) in over 98 percent of the cases.

  10. 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.

  11. Multi-Target Drugs for Neglected Diseases.

    PubMed

    Scotti, Luciana; Filho, Francisco J B M; de Moura, Ricardo O; Ribeiro, Frederico F; Ishiki, Hamilton; da Silva, Marcelo S; Filho, José M B; Scotti, Marcus T

    2016-05-30

    Diseases perceived as neglected tropical infections are generally caused by parasites which reach poor, underserved populations (primarily infrastructure), cause serious damage to health, and many deaths. AIDS and tuberculosis, (although not classified as neglected by WHO), are discriminated against infections which cause great social damage. The drugs currently used to treat these diseases do not have the desired effectiveness, enable the emergence of resistant strains, and in most cases are difficult to obtain. Few pharmaceutical companies are investing in new drug research for neglected diseases, for lack of financial return. This review reports the major neglected diseases, AIDS, tuberculosis, their targets, and research on multi-target drugs. The studies for new drugs against these infections involve in silico methods, synthesis, structural determinations, analytical analysis and other experimental assays. A new single compound, forecasting possible pharmacodynamic and pharmacokinetic interactions becomes a simpler process; it is also believed that these drugs are safer and more efficient, since they act with synergism on different targets. It occurs but the emergence of new resistant strains and side effects. Multi-target drugs represent a new alternative to find new lead compounds. A ligand that targets two or more receivers may be seen as a potential drug, combating infection by different routes.

  12. A Framework for Information Distribution, Task Execution and Decision Making in Multi-Robot Systems

    NASA Astrophysics Data System (ADS)

    Rambow, Matthias; Rohrmüller, Florian; Kourakos, Omiros; Bršcic, Drazen; Wollherr, Dirk; Hirche, Sandra; Buss, Martin

    Robotic systems operating in the real-world have to cope with unforeseen events by determining appropriate decisions based on noisy or partial knowledge. In this respect high functional robots are equipped with many sensors and actuators and run multiple processing modules in parallel. The resulting complexity is even further increased in case of cooperative multi-robot systems, since mechanisms for joint operation are needed. In this paper a complete and modular framework that handles this complexity in multi-robot systems is presented. It provides efficient exchange of generated data as well as a generic scheme for task execution and robot coordination.

  13. 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.

  14. Multi-Robot Dynamic Task Allocation Using Modified Ant Colony System

    NASA Astrophysics Data System (ADS)

    Xu, Zhenzhen; Xia, Feng; Zhang, Xianchao

    This paper presents a dynamic task allocation algorithm for multiple robots to visit multiple targets. This algorithm is specifically designed for the environment where robots have dissimilar starting and ending locations. And the constraint of balancing the number of targets visited by each robot is considered. More importantly, this paper takes into account the dynamicity of multi-robot system and the obstacles in the environment. This problem is modeled as a constrained MTSP which can not be transformed to TSP and can not be solved by classical Ant Colony System (ACS). The Modified Ant Colony System (MACS) is presented to solve this problem and the unvisited targets are allocated to appropriate robots dynamically. The simulation results show that the output of the proposed algorithm can satisfy the constraints and dynamicity for the problem of multi-robot task allocation.

  15. 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.

  16. 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.

  17. 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

  18. Multi-Robot Coalitions Formation with Deadlines: Complexity Analysis and Solutions

    PubMed Central

    2017-01-01

    Multi-robot task allocation is one of the main problems to address in order to design a multi-robot system, very especially when robots form coalitions that must carry out tasks before a deadline. A lot of factors affect the performance of these systems and among them, this paper is focused on the physical interference effect, produced when two or more robots want to access the same point simultaneously. To our best knowledge, this paper presents the first formal description of multi-robot task allocation that includes a model of interference. Thanks to this description, the complexity of the allocation problem is analyzed. Moreover, the main contribution of this paper is to provide the conditions under which the optimal solution of the aforementioned allocation problem can be obtained solving an integer linear problem. The optimal results are compared to previous allocation algorithms already proposed by the first two authors of this paper and with a new method proposed in this paper. The results obtained show how the new task allocation algorithms reach up more than an 80% of the median of the optimal solution, outperforming previous auction algorithms with a huge reduction of the execution time. PMID:28118384

  19. Multi-Robot Interfaces and Operator Situational Awareness: Study of the Impact of Immersion and Prediction

    PubMed Central

    Peña-Tapia, Elena; Martín-Barrio, Andrés; Olivares-Méndez, Miguel A.

    2017-01-01

    Multi-robot missions are a challenge for operators in terms of workload and situational awareness. These operators have to receive data from the robots, extract information, understand the situation properly, make decisions, generate the adequate commands, and send them to the robots. The consequences of excessive workload and lack of awareness can vary from inefficiencies to accidents. This work focuses on the study of future operator interfaces of multi-robot systems, taking into account relevant issues such as multimodal interactions, immersive devices, predictive capabilities and adaptive displays. Specifically, four interfaces have been designed and developed: a conventional, a predictive conventional, a virtual reality and a predictive virtual reality interface. The four interfaces have been validated by the performance of twenty-four operators that supervised eight multi-robot missions of fire surveillance and extinguishing. The results of the workload and situational awareness tests show that virtual reality improves the situational awareness without increasing the workload of operators, whereas the effects of predictive components are not significant and depend on their implementation. PMID:28749407

  20. 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

    2016-07-01

    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.

  1. Multi-Robot Coalitions Formation with Deadlines: Complexity Analysis and Solutions.

    PubMed

    Guerrero, Jose; Oliver, Gabriel; Valero, Oscar

    2017-01-01

    Multi-robot task allocation is one of the main problems to address in order to design a multi-robot system, very especially when robots form coalitions that must carry out tasks before a deadline. A lot of factors affect the performance of these systems and among them, this paper is focused on the physical interference effect, produced when two or more robots want to access the same point simultaneously. To our best knowledge, this paper presents the first formal description of multi-robot task allocation that includes a model of interference. Thanks to this description, the complexity of the allocation problem is analyzed. Moreover, the main contribution of this paper is to provide the conditions under which the optimal solution of the aforementioned allocation problem can be obtained solving an integer linear problem. The optimal results are compared to previous allocation algorithms already proposed by the first two authors of this paper and with a new method proposed in this paper. The results obtained show how the new task allocation algorithms reach up more than an 80% of the median of the optimal solution, outperforming previous auction algorithms with a huge reduction of the execution time.

  2. Multi-target therapeutics for neuropsychiatric and neurodegenerative disorders.

    PubMed

    Bawa, Priya; Pradeep, Priyamvada; Kumar, Pradeep; Choonara, Yahya E; Modi, Girish; Pillay, Viness

    2016-12-01

    Historically, neuropsychiatric and neurodegenerative disease treatments focused on the 'magic bullet' concept; however multi-targeted strategies are increasingly attractive gauging from the escalating research in this area. Because these diseases are typically co-morbid, multi-targeted drugs capable of interacting with multiple targets will expand treatment to the co-morbid disease condition. Despite their theoretical efficacy, there are significant impediments to clinical success (e.g., difficulty titrating individual aspects of the drug and inconclusive pathophysiological mechanisms). The new and revised diagnostic frameworks along with studies detailing the endophenotypic characteristics of the diseases promise to provide the foundation for the circumvention of these impediments. This review serves to evaluate the various marketed and nonmarketed multi-targeted drugs with particular emphasis on their design strategy.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Accurate multi-robot targeting for keyhole neurosurgery based on external sensor monitoring.

    PubMed

    Comparetti, Mirko Daniele; Vaccarella, Alberto; Dyagilev, Ilya; Shoham, Moshe; Ferrigno, Giancarlo; De Momi, Elena

    2012-05-01

    Robotics has recently been introduced in surgery to improve intervention accuracy, to reduce invasiveness and to allow new surgical procedures. In this framework, the ROBOCAST system is an optically surveyed multi-robot chain aimed at enhancing the accuracy of surgical probe insertion during keyhole neurosurgery procedures. The system encompasses three robots, connected as a multiple kinematic chain (serial and parallel), totalling 13 degrees of freedom, and it is used to automatically align the probe onto a desired planned trajectory. The probe is then inserted in the brain, towards the planned target, by means of a haptic interface. This paper presents a new iterative targeting approach to be used in surgical robotic navigation, where the multi-robot chain is used to align the surgical probe to the planned pose, and an external sensor is used to decrease the alignment errors. The iterative targeting was tested in an operating room environment using a skull phantom, and the targets were selected on magnetic resonance images. The proposed targeting procedure allows about 0.3 mm to be obtained as the residual median Euclidean distance between the planned and the desired targets, thus satisfying the surgical accuracy requirements (1 mm), due to the resolution of the diffused medical images. The performances proved to be independent of the robot optical sensor calibration accuracy.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. A switching formation strategy for obstacle avoidance of a multi-robot system based on robot priority model.

    PubMed

    Dai, Yanyan; Kim, YoonGu; Wee, SungGil; Lee, DongHa; Lee, SukGyu

    2015-05-01

    This paper describes a switching formation strategy for multi-robots with velocity constraints to avoid and cross obstacles. In the strategy, a leader robot plans a safe path using the geometric obstacle avoidance control method (GOACM). By calculating new desired distances and bearing angles with the leader robot, the follower robots switch into a safe formation. With considering collision avoidance, a novel robot priority model, based on the desired distance and bearing angle between the leader and follower robots, is designed during the obstacle avoidance process. The adaptive tracking control algorithm guarantees that the trajectory and velocity tracking errors converge to zero. To demonstrate the validity of the proposed methods, simulation and experiment results present that multi-robots effectively form and switch formation avoiding obstacles without collisions.

  20. 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

  1. 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.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Zak, Michail; Toomarian, Nikzad

    1991-08-01

    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.

  4. Deterministic optimal maneuver strategy for multi-target missions

    NASA Technical Reports Server (NTRS)

    Dwivedi, N. P.

    1975-01-01

    This paper presents an optimal strategy for making impulsive correction to a multi-target trajectory by a single maneuver. The concept of an optimal maneuver time is introduced. The choice of suitable weighting functions is explored to enable one to properly translate the subjective desire of mission success into an objective cost function whose minimization yields the optimal strategy. It is shown that a number of strategies previously formulated are derivable from one general expression. A number of other interesting properties of the optimal strategy are described. Numerical results are presented for a typical two-target mission. It is shown that the strategy formulated is optimal. For some perturbations, there exists an optimal maneuver time different from the time of initiation of the perturbation. That is, the physical properties of the trajectory can be exploited to select the optimal time of making a corrective maneuver.

  5. 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.

  6. 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.

  7. Hitchhiking Robots: A Collaborative Approach for Efficient Multi-Robot Navigation in Indoor Environments.

    PubMed

    Ravankar, Abhijeet; Ravankar, Ankit A; Kobayashi, Yukinori; Emaru, Takanori

    2017-08-15

    Hitchhiking is a means of transportation gained by asking other people for a (free) ride. We developed a multi-robot system which is the first of its kind to incorporate hitchhiking in robotics, and discuss its advantages. Our method allows the hitchhiker robot to skip redundant computations in navigation like path planning, localization, obstacle avoidance, and map update by completely relying on the driver robot. This allows the hitchhiker robot, which performs only visual servoing, to save computation while navigating on the common path with the driver robot. The driver robot, in the proposed system performs all the heavy computations in navigation and updates the hitchhiker about the current localized positions and new obstacle positions in the map. The proposed system is robust to recover from `driver-lost' scenario which occurs due to visual servoing failure. We demonstrate robot hitchhiking in real environments considering factors like service-time and task priority with different start and goal configurations of the driver and hitchhiker robots. We also discuss the admissible characteristics of the hitchhiker, when hitchhiking should be allowed and when not, through experimental results.

  8. Hitchhiking Robots: A Collaborative Approach for Efficient Multi-Robot Navigation in Indoor Environments

    PubMed Central

    Ravankar, Abhijeet; Ravankar, Ankit A.; Kobayashi, Yukinori; Emaru, Takanori

    2017-01-01

    Hitchhiking is a means of transportation gained by asking other people for a (free) ride. We developed a multi-robot system which is the first of its kind to incorporate hitchhiking in robotics, and discuss its advantages. Our method allows the hitchhiker robot to skip redundant computations in navigation like path planning, localization, obstacle avoidance, and map update by completely relying on the driver robot. This allows the hitchhiker robot, which performs only visual servoing, to save computation while navigating on the common path with the driver robot. The driver robot, in the proposed system performs all the heavy computations in navigation and updates the hitchhiker about the current localized positions and new obstacle positions in the map. The proposed system is robust to recover from ‘driver-lost’ scenario which occurs due to visual servoing failure. We demonstrate robot hitchhiking in real environments considering factors like service-time and task priority with different start and goal configurations of the driver and hitchhiker robots. We also discuss the admissible characteristics of the hitchhiker, when hitchhiking should be allowed and when not, through experimental results. PMID:28809803

  9. 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

  10. 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.

  11. Real-Time Multi-Target Localization from Unmanned Aerial Vehicles.

    PubMed

    Wang, Xuan; Liu, Jinghong; Zhou, Qianfei

    2016-12-25

    In order to improve the reconnaissance efficiency of unmanned aerial vehicle (UAV) electro-optical stabilized imaging systems, a real-time multi-target localization scheme based on an UAV electro-optical stabilized imaging system is proposed. First, a target location model is studied. Then, the geodetic coordinates of multi-targets are calculated using the homogeneous coordinate transformation. On the basis of this, two methods which can improve the accuracy of the multi-target localization are proposed: (1) the real-time zoom lens distortion correction method; (2) a recursive least squares (RLS) filtering method based on UAV dead reckoning. The multi-target localization error model is established using Monte Carlo theory. In an actual flight, the UAV flight altitude is 1140 m. The multi-target localization results are within the range of allowable error. After we use a lens distortion correction method in a single image, the circular error probability (CEP) of the multi-target localization is reduced by 7%, and 50 targets can be located at the same time. The RLS algorithm can adaptively estimate the location data based on multiple images. Compared with multi-target localization based on a single image, CEP of the multi-target localization using RLS is reduced by 25%. The proposed method can be implemented on a small circuit board to operate in real time. This research is expected to significantly benefit small UAVs which need multi-target geo-location functions.

  12. Real-Time Multi-Target Localization from Unmanned Aerial Vehicles

    PubMed Central

    Wang, Xuan; Liu, Jinghong; Zhou, Qianfei

    2016-01-01

    In order to improve the reconnaissance efficiency of unmanned aerial vehicle (UAV) electro-optical stabilized imaging systems, a real-time multi-target localization scheme based on an UAV electro-optical stabilized imaging system is proposed. First, a target location model is studied. Then, the geodetic coordinates of multi-targets are calculated using the homogeneous coordinate transformation. On the basis of this, two methods which can improve the accuracy of the multi-target localization are proposed: (1) the real-time zoom lens distortion correction method; (2) a recursive least squares (RLS) filtering method based on UAV dead reckoning. The multi-target localization error model is established using Monte Carlo theory. In an actual flight, the UAV flight altitude is 1140 m. The multi-target localization results are within the range of allowable error. After we use a lens distortion correction method in a single image, the circular error probability (CEP) of the multi-target localization is reduced by 7%, and 50 targets can be located at the same time. The RLS algorithm can adaptively estimate the location data based on multiple images. Compared with multi-target localization based on a single image, CEP of the multi-target localization using RLS is reduced by 25%. The proposed method can be implemented on a small circuit board to operate in real time. This research is expected to significantly benefit small UAVs which need multi-target geo-location functions. PMID:28029145

  13. MULTI-TARGETED THERAPY OF CANCER BY GENISTEIN

    PubMed Central

    BANERJEE, SANJEEV; LI, YIWEI; WANG, ZHIWEI; SARKAR, FAZLUL H.

    2008-01-01

    Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen- and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells. PMID:18492603

  14. Multi-target pursuit formation of multi-agent systems

    NASA Astrophysics Data System (ADS)

    Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

    2011-01-01

    The main goal of this paper is to design a team of agents that can accomplish multi-target pursuit formation using a developed leader—follower strategy. It is supposed that every target can accept a certain number of agents. First, each agent can automatically choose its target based on the distance from the agent to the target and the number of agents accepted by the target. In view of the fact that all agents are randomly dispersed in the workplace at the initial time, we present a numbering strategy for them. During the movement of agents, not every agent can always obtain pertinent state information about the targets. So, a developed leader—follower strategy and a pursuit formation algorithm are proposed. Under the proposed method, agents with the same target can maintain a circle formation. Furthermore, it turns out that the pursuit formation algorithm for agents to the desired formation is convergent. Simulation studies are provided to illustrate the effectiveness of the proposed method.

  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. Multi-Target Tracking by Discrete-Continuous Energy Minimization.

    PubMed

    Milan, Anton; Schindler, Konrad; Roth, Stefan

    2016-10-01

    The task of tracking multiple targets is often addressed with the so-called tracking-by-detection paradigm, where the first step is to obtain a set of target hypotheses for each frame independently. Tracking can then be regarded as solving two separate, but tightly coupled problems. The first is to carry out data association, i.e., to determine the origin of each of the available observations. The second problem is to reconstruct the actual trajectories that describe the spatio-temporal motion pattern of each individual target. The former is inherently a discrete problem, while the latter should intuitively be modeled in continuous space. Having to deal with an unknown number of targets, complex dependencies, and physical constraints, both are challenging tasks on their own and thus most previous work focuses on one of these subproblems. Here, we present a multi-target tracking approach that explicitly models both tasks as minimization of a unified discrete-continuous energy function. Trajectory properties are captured through global label costs, a recent concept from multi-model fitting, which we introduce to tracking. Specifically, label costs describe physical properties of individual tracks, e.g., linear and angular dynamics, or entry and exit points. We further introduce pairwise label costs to describe mutual interactions between targets in order to avoid collisions. By choosing appropriate forms for the individual energy components, powerful discrete optimization techniques can be leveraged to address data association, while the shapes of individual trajectories are updated by gradient-based continuous energy minimization. The proposed method achieves state-of-the-art results on diverse benchmark sequences.

  17. 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

    2016-08-10

    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.

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

    PubMed Central

    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

  19. Applications of Multi-Target Computer-Aided Methodologies in Molecular Design of CNS Drugs.

    PubMed

    Raevsky, Oleg A; Mukhametov, Azat; Grigorev, Veniamin Y; Ustyugov, Alexey; Tsay, Shwu-Chen; Jih-Ru Hwu, Reuben; Yarla, Nagendra Sastry; Barreto, George E; Aliev, Gjumrakch; Bachurin, Sergey O

    2017-09-20

    : Discovery of drugs for diseases of the central nervous system (CNS) faces high attrition rates in clinical trials. Neural diseases are extremely complex in nature and typically associated with multiple drug targets. A conception of multi-target directed ligands (MTDL), widely applied to discovery of cancer pharmaceuticals, may be a perspective solution for CNS diseases. Special bio-informatics approaches have been developed which can assist the medicinal chemists in identification and structural optimization of MTDL. In this review, we analyze the current status of development of multi-target approaches in quantitative structure-activity relationships (mt-QSAR) for CNS drug discovery; and describe applications of multi-target approaches in molecular modelling (which can be called mt-MM) as well as perspectives for multi-target approaches in bio-informatics in relation to Alzheimer&apos's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. 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

  1. The role of multi-target policy instruments in agri-environmental policy mixes.

    PubMed

    Schader, Christian; Lampkin, Nicholas; Muller, Adrian; Stolze, Matthias

    2014-12-01

    The Tinbergen Rule has been used to criticise multi-target policy instruments for being inefficient. The aim of this paper is to clarify the role of multi-target policy instruments using the case of agri-environmental policy. Employing an analytical linear optimisation model, this paper demonstrates that there is no general contradiction between multi-target policy instruments and the Tinbergen Rule, if multi-target policy instruments are embedded in a policy-mix with a sufficient number of targeted instruments. We show that the relation between cost-effectiveness of the instruments, related to all policy targets, is the key determinant for an economically sound choice of policy instruments. If economies of scope with respect to achieving policy targets are realised, a higher cost-effectiveness of multi-target policy instruments can be achieved. Using the example of organic farming support policy, we discuss several reasons why economies of scope could be realised by multi-target agri-environmental policy instruments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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.

  4. Temporal Clustering in the Multi-Target Tracking Environment

    DTIC Science & Technology

    1988-08-01

    found in high-energy particle physics, fluid mechanics , and ballistic missile defense, the common ob- jective is to separate the data into observations...use has been an immense help in simplifying the mechanics of producing this dissertation, allowing me to concentrate more fully on its content... mechanics , and ballistic missile defense, the common ob- jective is to separate the data into observations associated with individual targets and to

  5. 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.

  6. Design and preliminary evaluation of a multi-robotic system with pelvic and hip assistance for pediatric gait rehabilitation.

    PubMed

    Park, Evelyn J; Kang, Jiyeon; Su, Hao; Stegall, Paul; Miranda, Daniel L; Hsu, Wen-Hao; Karabas, Mustafa; Phipps, Nathan; Agrawal, Sunil K; Goldfield, Eugene C; Walsh, Conor J

    2017-07-01

    This paper presents a modular, computationally-distributed "multi-robot" cyberphysical system designed to assist children with developmental delays in learning to walk. The system consists of two modules, each assisting a different aspect of gait: a tethered cable pelvic module with up to 6 degrees of freedom (DOF), which can modulate the motion of the pelvis in three dimensions, and a two DOF wearable hip module assisting lower limb motion, specifically hip flexion. Both modules are designed to be lightweight and minimally restrictive to the user, and the modules can operate independently or in cooperation with each other, allowing flexible system configuration to provide highly customized and adaptable assistance. Motion tracking performance of approximately 2 mm root mean square (RMS) error for the pelvic module and less than 0.1 mm RMS error for the hip module was achieved. We demonstrate coordinated operation of the two modules on a mannequin test platform with articulated and instrumented lower limbs.

  7. Multi-Target Tracking in Video - Part II

    NASA Astrophysics Data System (ADS)

    Zheng, Nanning; Xue, Jianru

    This chapter presents a sequential Monte Carlo data association algorithm for tracking a varying number of interacting objects in a dynamic scene. The algorithm is based on a computational framework that consists of a hybrid measurement process, a Monte Carlo joint probabilistic data association filter, and a particle-based belief propagation algorithm. The hybrid measurement process addresses problems associated with having a varying number of objects. It does so by mixing target-driven measurements provided by a prior model of target dynamics and data-driven measurements based on a discriminative model; the Monte Carlo joint probabilistic data association filter combats the curse of dimensionality by providing a marginal posterior distribution for each individual target; and particle-based belief propagation is used to deal with occlusions among objects.Within this framework, the learning of discriminative model, the Monte Carlo joint data association filtering, and belief propagation are realized as different levels of approximation to the ‘ideal’ generative model inherent in the problem of tracking multiple visual objects. Together, these result in an efficient sequential Monte Carlo data association algorithm. The algorithm is illustrated via the tracking of multiple pedestrians in several real-life test videos. Empirical results demonstrate the algorithm’s efficiency in a number of test situations.

  8. 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.

  9. Multi-targeted hybrids based on HDAC inhibitors for anti-cancer drug discovery.

    PubMed

    Seo, Seung-Yong

    2012-02-01

    Multi-targeted hybrids combine two drugs in a single molecule to have greater medicinal effects than its individual components. Recently, a number of anti-cancer drug candidates such as CUDC-101 (Curis) have been designed based on linking properly two selected pharmacophores endowed with activity against different therapeutic targets.

  10. Performance of a class of multi-robot deploy and search strategies based on centroidal voronoi configurations

    NASA Astrophysics Data System (ADS)

    Guruprasad, K. R.; Ghose, Debasish

    2013-04-01

    This article considers a class of deploy and search strategies for multi-robot systems and evaluates their performance. The application framework used is deployment of a system of autonomous mobile robots equipped with required sensors in a search space to gather information. The lack of information about the search space is modelled as an uncertainty density distribution. The agents are deployed to maximise single-step search effectiveness. The centroidal Voronoi configuration, which achieves a locally optimal deployment, forms the basis for sequential deploy and search (SDS) and combined deploy and search (CDS) strategies. Completeness results are provided for both search strategies. The deployment strategy is analysed in the presence of constraints on robot speed and limit on sensor range for the convergence of trajectories with corresponding control laws responsible for the motion of robots. SDS and CDS strategies are compared with standard greedy and random search strategies on the basis of time taken to achieve reduction in the uncertainty density below a desired level. The simulation experiments reveal several important issues related to the dependence of the relative performances of the search strategies on parameters such as the number of robots, speed of robots and their sensor range limits.

  11. Symmetrizing measurement equations for association-free multi-target tracking via point set distances

    NASA Astrophysics Data System (ADS)

    Hanebeck, Uwe D.; Baum, Marcus; Willett, Peter

    2017-05-01

    We are tracking multiple targets based on noisy measurements. The targets are labeled, the measurements are unlabeled, and the association of measurements to targets is unknown. Our goal is association-free tracking, so the associations will never be determined as this is costly and impractical in many scenarios. By employing a permutation-invariant and differentiable point set distance measure, we derive a modified association-free multi-target measurement equation. It maintains the target identities but is invariant to permutations in the unlabeled measurements. Based on this measurement equation, we derive an efficient sample-based association-free multi-target Kalman filter. The proposed new approach is straightforward to implement and scalable.

  12. Development of RNA interference-based therapeutics and application of multi-target small interfering RNAs.

    PubMed

    Li, Tiejun; Wu, Meihua; Zhu, York Yuanyuan; Chen, Jianxin; Chen, Li

    2014-08-01

    RNA interference (RNAi) has been proven in recent years to be a newly advanced and powerful tool for development of therapeutic agents toward various unmet medical needs such as cancer, in particular, a great attention has been paid to the development of antineoplastic agents. Recent success in clinical trials related to RNAi-based therapeutics on cancer and ocular disease has validated that small interfering RNAs (siRNAs) constitute a new promising class of therapeutics. Currently, a great wealth of multi-target based siRNA structural modifications is available for promoting siRNA-mediated gene silencing with low side effects. Here, the latest developments in RNAi-based therapeutics and novel structural modifications described for siRNAs--in particular multi-target siRNAs--are reviewed.

  13. Multi-target drug design approaches for multifactorial diseases: from neurodegenerative to cardiovascular applications.

    PubMed

    Katselou, M G; Matralis, A N; Kourounakis, A P

    2014-01-01

    In multi-target drug design (MTD) medicinal chemistry aims to integrate multiple pharmacophores into a single drug molecule in order to make it active on several molecular biological mechanisms simultaneously. Given the fact that most diseases are multifactorial in nature, MTD is being pursued with increasing intensity, which has resulted in improved outcomes in disease models and several compounds have entered clinical trials. In a wide range of examples we illustrate how various functionalities have been combined within single structures and how this has affected their (pre)clinical outcome. This review describes the successful application of MTD for disorders such as neurodegenerative, cardiovascular, diabetes, metabolic and inflammatory diseases, especially focusing on the field of atherosclerosis where multi-target strategies are a promising alternative to the classical "one target-one drug" design approach.

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

    PubMed Central

    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

  15. Systematic mining of analog series with related core structures in multi-target activity space.

    PubMed

    Gupta-Ostermann, Disha; Hu, Ye; Bajorath, Jürgen

    2013-08-01

    We have aimed to systematically extract analog series with related core structures from multi-target activity space to explore target promiscuity of closely related analogous. Therefore, a previously introduced SAR matrix structure was adapted and further extended for large-scale data mining. These matrices organize analog series with related yet distinct core structures in a consistent manner. High-confidence compound activity data yielded more than 2,300 non-redundant matrices capturing 5,821 analog series that included 4,288 series with multi-target and 735 series with multi-family activities. Many matrices captured more than three analog series with activity against more than five targets. The matrices revealed a variety of promiscuity patterns. Compound series matrices also contain virtual compounds, which provide suggestions for compound design focusing on desired activity profiles.

  16. Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer's disease.

    PubMed

    Jeřábek, Jakub; Uliassi, Elisa; Guidotti, Laura; Korábečný, Jan; Soukup, Ondřej; Sepsova, Vendula; Hrabinova, Martina; Kuča, Kamil; Bartolini, Manuela; Peña-Altamira, Luis Emiliano; Petralla, Sabrina; Monti, Barbara; Roberti, Marinella; Bolognesi, Maria Laura

    2017-02-15

    Multi-target drug discovery is one of the most followed approaches in the active central nervous system (CNS) therapeutic area, especially in the search for new drugs against Alzheimer's disease (AD). This is because innovative multi-target-directed ligands (MTDLs) could more adequately address the complexity of this pathological condition. In a continuation of our efforts aimed at a new series of anti-AD MTDLs, we combined the structural features of the cholinesterase inhibitor drug tacrine with that of resveratrol, which is known for its purported antioxidant and anti-neuroinflammatory activities. The most interesting hybrid compounds (5, 8, 9 and 12) inhibited human acetylcholinesterase at micromolar concentrations and effectively modulated Aβ self-aggregation in vitro. In addition, 12 showed intriguing anti-inflammatory and immuno-modulatory properties in neuronal and glial AD cell models. Importantly, the MTDL profile is accompanied by high-predicted blood-brain barrier permeability, and low cytotoxicity on primary neurons.

  17. Zebrafish behavioral profiling identifies multi-target antipsychotic-like compounds

    PubMed Central

    Bruni, Giancarlo; Rennekamp, Andrew J.; Velenich, Andrea; McCarroll, Matthew; Gendelev, Leo; Fertsch, Ethan; Taylor, Jack; Lakhani, Parth; Lensen, Dennis; Evron, Tama; Lorello, Paul J.; Huang, Xi-Ping; Kolczewski, Sabine; Carey, Galen; Caldarone, Barbara J.; Prinssen, Eric; Roth, Bryan L.; Keiser, Michael J.; Peterson, Randall T.; Kokel, David

    2016-01-01

    Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping, and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action based on their behavioral profiles alone. Although zebrafish (Danio rerio) behaviors have been used to rapidly identify neuroactive compounds, it remains unclear exactly what kind of behavioral assays might be necessary to identify multi-target compounds such as antipsychotics. Here, we developed a battery of behavioral assays in larval zebrafish to determine if behavioral profiles could provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated animals could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multi-target mechanisms of action. PMID:27239787

  18. Multi-Target Screening and Experimental Validation of Natural Products from Selaginella Plants against Alzheimer's Disease.

    PubMed

    Deng, Yin-Hua; Wang, Ning-Ning; Zou, Zhen-Xing; Zhang, Lin; Xu, Kang-Ping; Chen, Alex F; Cao, Dong-Sheng; Tan, Gui-Shan

    2017-01-01

    Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder which is considered to be the most common cause of dementia. It has a greater impact not only on the learning and memory disturbances but also on social and economy. Currently, there are mainly single-target drugs for AD treatment but the complexity and multiple etiologies of AD make them difficult to obtain desirable therapeutic effects. Therefore, the choice of multi-target drugs will be a potential effective strategy inAD treatment. To find multi-target active ingredients for AD treatment from Selaginella plants, we firstly explored the behaviors effects on AD mice of total extracts (TE) from Selaginella doederleinii on by Morris water maze test and found that TE has a remarkable improvement on learning and memory function for AD mice. And then, multi-target SAR models associated with AD-related proteins were built based on Random Forest (RF) and different descriptors to preliminarily screen potential active ingredients from Selaginella. Considering the prediction outputs and the quantity of existing compounds in our laboratory, 13 compounds were chosen to carry out the in vitro enzyme inhibitory experiments and 4 compounds with BACE1/MAO-B dual inhibitory activity were determined. Finally, the molecular docking was applied to verify the prediction results and enzyme inhibitory experiments. Based on these study and validation processes, we explored a new strategy to improve the efficiency of active ingredients screening based on trace amount of natural product and numbers of targets and found some multi-target compounds with biological activity for the development of novel drugs for AD treatment.

  19. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

    PubMed

    Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

    2017-08-18

    The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Multi-target pharmacology: possibilities and limitations of the "skeleton key approach" from a medicinal chemist perspective.

    PubMed

    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.

  1. Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far.

    PubMed

    Bordoloi, Devivasha; Roy, Nand K; Monisha, Javadi; Padmavathi, Ganesan; Kunnumakkara, Ajaikumar B

    2016-01-01

    Research over the past several years has developed many mono-targeted therapies for the prevention and treatment of cancer, but it still remains one of the fatal diseases in the world killing 8.2 million people annually. It has been well-established that development of chemoresistance in cancer cells against mono-targeted chemotherapeutic agents by modulation of multiple survival pathways is the major cause of failure of cancer chemotherapy. Therefore, inhibition of these pathways by non-toxic multi-targeted agents may have profoundly high potential in preventing drug resistance and sensitizing cancer cells to chemotherapeutic agents. To study the potential of curcumin, a multi-targeted natural compound, obtained from the plant Turmeric (Curcuma longa) in combination with standard chemotherapeutic agents to inhibit drug resistance and sensitize cancer cells to these agents based on available literature and patents. An extensive literature survey was performed in PubMed and Google for the chemosensitizing potential of curcumin in different cancers published so far and the patents published during 2014-2015. Our search resulted in many in vitro, in vivo and clinical reports signifying the chemosensitizing potential of curcumin in diverse cancers. There were 160 in vitro studies, 62 in vivo studies and 5 clinical studies. Moreover, 11 studies reported on hybrid curcumin: the next generation of curcumin based therapeutics. Also, 34 patents on curcumin's biological activity have been retrieved. Altogether, the present study reveals the enormous potential of curcumin, a natural, non-toxic, multi-targeted agent in overcoming drug resistance in cancer cells and sensitizing them to chemotherapeutic drugs.

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

    PubMed

    Rosenbaum, Lars; Dörr, Alexander; Bauer, Matthias R; Boeckler, Frank M; Zell, Andreas

    2013-07-11

    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. 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. 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.

  3. Adaptive Collaborative Gaussian Mixture Probability Hypothesis Density Filter for Multi-Target Tracking.

    PubMed

    Yang, Feng; Wang, Yongqi; Chen, Hao; Zhang, Pengyan; Liang, Yan

    2016-10-11

    In this paper, an adaptive collaborative Gaussian Mixture Probability Hypothesis Density (ACo-GMPHD) filter is proposed for multi-target tracking with automatic track extraction. Based on the evolutionary difference between the persistent targets and the birth targets, the measurements are adaptively partitioned into two parts, persistent and birth measurement sets, for updating the persistent and birth target Probability Hypothesis Density, respectively. Furthermore, the collaboration mechanism of multiple probability hypothesis density (PHDs) is established, where tracks can be automatically extracted. Simulation results reveal that the proposed filter yields considerable computational savings in processing requirements and significant improvement in tracking accuracy.

  4. In silico search for multi-target anti-inflammatories in Chinese herbs and formulas.

    PubMed

    Ehrman, Thomas M; Barlow, David J; Hylands, Peter J

    2010-03-15

    Chinese herbs were screened for compounds which may be active against four targets involved in inflammation, using pharmacophore-assisted docking. Multiple LigandScout (LS) pharmacophores built from ligand-receptor complexes in the protein databank (PDB) were first employed to select compounds. These compounds were then docked using LS-derived templates and ranked according to docking score. The targets comprised cyclo-oxygenases 1 & 2 (COX), p38 MAP kinase (p38), c-Jun terminal-NH(2) kinase (JNK) and type 4 cAMP-specific phosphodiesterase (PDE4). The results revealed that multi-target inhibitors are likely to be relatively common in Chinese herbs. Details of their distribution are given, in addition to experimental evidence supporting these results. Examples of compounds predicted to be active against at least three targets are presented, and their features outlined. The distribution of herbs containing predicted inhibitors was also analysed in relation to 192 Chinese formulas from over 50 herbal categories. Among those found to contain a high proportion of these herbs were formulas traditionally used to treat fever, headache, rheumatoid arthritis, inflammatory bowel disorders, skin disease, cancer, and traumatic injury. Relationships between multi-target drug discovery and Chinese medicine are discussed.

  5. 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

    2016-02-22

    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.

  6. 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

  7. Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs.

    PubMed

    Tao, Lin; Zhu, Feng; Xu, Feng; Chen, Zhe; Jiang, Yu Yang; Chen, Yu Zong

    2015-12-01

    Recent investigations have suggested that anticancer therapeutics may be enhanced by co-targeting the primary anticancer target and the corresponding drug escape pathways. Whether this strategy confers statistically significant clinical advantage has not been systematically investigated. This question was probed by the evaluation of the clinical status and the multiple targets of 23 approved and 136 clinical trial multi-target anticancer drugs with particular focus on those co-targeting EGFR, HER2, Abl, VEGFR2, mTOR, PI3K, Alk, MEK, KIT, and DNA topoisomerase, and some of the 14, 7, 13, 20, 6, 5, 7, 2, 4 and 10 cancer drug escape pathways respectively. Most of the approved (73.9%) and phase III (75.0%), the majority of the Phase II (62.8%) and I (53.6%), and the minority of the discontinued (35.3%) multi-target drugs were found to co-target cancer drug escape pathways. This suggests that co-targeting anticancer targets and drug escape pathways confer significant clinical advantage and such strategy can be more extensively explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

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

    PubMed

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

    2015-11-06

    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.

  11. Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease.

    PubMed

    Orhan, Ilkay Erdogan; Senol, F Sezer

    2016-01-01

    Due to multi-faceted pathology of AD; no drug can seize the progress of the disease, whereas only the symptomatic treatment is available at the moment. Several drug classes to treat AD are available in clinical use, AChEIs being the most prescribed. In addition to AChEIs, secretase enzymes and iron chelators have turned out to be the focus of research and the popular targets in drug discovery against AD. The latest approaches such as immunotherapy, multi-targeted drug ligand design, AChE inhibitors, antioxidants, metal chelators, monoamine oxidase (MAO) inhibitors, antiinflammatory drugs, and N-methyl-D-aspartate (NMDA) inhibitors are currently in use to cure this disease to some extent. But, there is a certain need to develop new drugs to fight with AD, particularly acting on multi-targets or with dual mechanisms of action. In this review, a particular emphasis will be focused on multitargets aiming at AD to design new drug molecules with respect to treatment strategies and preventive measures. Since the underlying pathogenesis of AD is complicated and still under investigation, the attempts to design highly selective and potent agents to treat AD are quite intensively continuing. In this respect, designing novel drugs with dual/multi-acting mechanisms seems to be more rational.

  12. 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

  13. Role of moving average analysis for development of multi-target (Q)SAR models.

    PubMed

    Khatri, N; Dutt, R; Madan, A K

    2015-01-01

    In modern drug discovery era, multi target- quantitative structure activity relationship [mt- (Q)SAR] approaches have emerged as novel and powerful alternatives in the field of in-silico drug design so as to facilitate the discovery of new chemical entities with multiple biological activities. Amongst various machine learning approaches, moving average analysis (MAA) has frequently exhibited high accuracy of prediction of diverse biological activities against different biological targets and experimental conditions. Role of MAA in developing (Q)SAR models for prediction of single/dual or multi target activity has been briefly reviewed in the present article. Subsequently, MAA was successfully utilized for developing mt-(Q)SAR models for simultaneous prediction of anti-Plasmodium falciparum and anti-Trypanosoma brucei rhodesiense activities of benzyl phenyl ether derivatives. The statistical significance of models was assessed through intercorrelation analysis, sensitivity, specificity and Matthew's correlation coefficient. Proposed MAA based models were also validated using test set. High predictability of the order of 80% to 95% amalgamated with safety (indicated by high value of selectivity index) of proposed mt-(Q)SAR models justifies use of MAA in developing models in order to obtain more realistic and accurate results for prediction of anti-protozal activity against multiple targets. Active ranges of the proposed models can play a significant role in the development of novel, potent, versatile and safe anti-protozoal drugs with improved profile in terms of both anti-Plasmodium falciparum and anti-Trypanosoma brucei rhodesiense activities.

  14. A Parallel Finite Set Statistical Simulator for Multi-Target Detection and Tracking

    NASA Astrophysics Data System (ADS)

    Hussein, I.; MacMillan, R.

    2014-09-01

    Finite Set Statistics (FISST) is a powerful Bayesian inference tool for the joint detection, classification and tracking of multi-target environments. FISST is capable of handling phenomena such as clutter, misdetections, and target birth and decay. Implicit within the approach are solutions to the data association and target label-tracking problems. Finally, FISST provides generalized information measures that can be used for sensor allocation across different types of tasks such as: searching for new targets, and classification and tracking of known targets. These FISST capabilities have been demonstrated on several small-scale illustrative examples. However, for implementation in a large-scale system as in the Space Situational Awareness problem, these capabilities require a lot of computational power. In this paper, we implement FISST in a parallel environment for the joint detection and tracking of multi-target systems. In this implementation, false alarms and misdetections will be modeled. Target birth and decay will not be modeled in the present paper. We will demonstrate the success of the method for as many targets as we possibly can in a desktop parallel environment. Performance measures will include: number of targets in the simulation, certainty of detected target tracks, computational time as a function of clutter returns and number of targets, among other factors.

  15. 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.

  16. XAX: A multi-ton, multi-target detection system for dark matter, double beta decay and pp solar neutrinos

    NASA Astrophysics Data System (ADS)

    Arisaka, K.; Wang, H.; Smith, P. F.; Cline, D.; Teymourian, A.; Brown, E.; Ooi, W.; Aharoni, D.; Lam, C. W.; Lung, K.; Davies, S.; Price, M.

    2009-03-01

    A multi-target detection system XAX, comprising concentric 10 ton targets of 136Xe and 129/131Xe, together with a geometrically similar or larger target of liquid Ar, is described. Each is configured as a two-phase scintillation/ionization TPC detector, enhanced by a full 4π array of ultra-low radioactivity quartz photon intensifying detectors (QUPIDs) replacing the conventional photomultipliers for detection of scintillation light. It is shown that background levels in XAX can be reduced to the level required for dark matter particle (WIMP) mass measurement at a 10-10 pb WIMP-nucleon cross-section, with single-event sensitivity below 10-11 pb. The use of multiple target elements allows for confirmation of the A2 dependence of a coherent cross-section, and the different Xe isotopes provide information on the spin-dependence of the dark matter interaction. The event rates observed by Xe and Ar would modulate annually with opposite phases from each other for WIMP mass >˜100 GeV/c2. The large target mass of 136Xe and high degree of background reduction allow neutrinoless double beta decay to be observed with lifetimes of 1027 1028 years, corresponding to the Majorana neutrino mass range 0.01 0.1 eV, the most likely range from observed neutrino mass differences. The use of a 136Xe-depleted 129/131Xe target will also allow measurement of the pp solar neutrino spectrum to a precision of 1 2%.

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

    PubMed Central

    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

  18. Ultrasound in systemic sclerosis. A multi-target approach from joint to lung.

    PubMed

    Gutierrez, Marwin; Pineda, Carlos; Cazenave, Tomas; Piras, Marco; Erre, Gian Luca; Draghessi, Antonella; De Angelis, Rossella; Grassi, Walter

    2014-08-01

    Ultrasound (US) is a cost-effective, noninvasive, accessible imaging modality that clinicians use at the point of care to assess disease activity and therapeutic efficacy in different rheumatic conditions. However, its utility has been prevalently demonstrated in the field of chronic arthritides. Only in the last few years there was an interest to explore the potential of US beyond the musculoskeletal area. In this way, preliminary US data about the assessment of the different targets involved in systemic sclerosis such as joints, tendons, skin, vessels, and lung have been provided. The main purpose of this US review is to provide an overview of the potential role of US in the multi-target assessment of SSc and to discuss the current evidence supporting its relevance and applications in daily clinical practice.

  19. Discovery of multi-target receptor tyrosine kinase inhibitors as novel anti-angiogenesis agents

    NASA Astrophysics Data System (ADS)

    Wang, Jinfeng; Zhang, Lin; Pan, Xiaoyan; Dai, Bingling; Sun, Ying; Li, Chuansheng; Zhang, Jie

    2017-03-01

    Recently, we have identified a biphenyl-aryl urea incorporated with salicylaldoxime (BPS-7) as an anti-angiogenesis agent. Herein, we disclosed a series of novel anti-angiogenesis agents with BPS-7 as lead compound through combining diarylureas with N-pyridin-2-ylcyclopropane carboxamide. Several title compounds exhibited simultaneous inhibition effects against three pro-angiogenic RTKs (VEGFR-2, TIE-2 and EphB4). Some of them displayed potent anti-proliferative activity against human vascular endothelial cell (EA.hy926). In particular, two potent compounds (CDAU-1 and CDAU-2) could be considered as promising anti-angiogenesis agents with triplet inhibition profile. The biological evaluation and molecular docking results indicate that N-pyridin-2-ylcyclopropane carboxamide could serve as a hinge-binding group (HBG) for the discovery of multi-target anti-angiogenesis agents. CDAU-2 also exhibited promising anti-angiogenic potency in a tissue model for angiogenesis.

  20. Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods

    PubMed Central

    Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J.

    2017-01-01

    We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter. PMID:28273796

  1. Discovery of multi-target receptor tyrosine kinase inhibitors as novel anti-angiogenesis agents

    PubMed Central

    Wang, Jinfeng; Zhang, Lin; Pan, Xiaoyan; Dai, Bingling; Sun, Ying; Li, Chuansheng; Zhang, Jie

    2017-01-01

    Recently, we have identified a biphenyl-aryl urea incorporated with salicylaldoxime (BPS-7) as an anti-angiogenesis agent. Herein, we disclosed a series of novel anti-angiogenesis agents with BPS-7 as lead compound through combining diarylureas with N-pyridin-2-ylcyclopropane carboxamide. Several title compounds exhibited simultaneous inhibition effects against three pro-angiogenic RTKs (VEGFR-2, TIE-2 and EphB4). Some of them displayed potent anti-proliferative activity against human vascular endothelial cell (EA.hy926). In particular, two potent compounds (CDAU-1 and CDAU-2) could be considered as promising anti-angiogenesis agents with triplet inhibition profile. The biological evaluation and molecular docking results indicate that N-pyridin-2-ylcyclopropane carboxamide could serve as a hinge-binding group (HBG) for the discovery of multi-target anti-angiogenesis agents. CDAU-2 also exhibited promising anti-angiogenic potency in a tissue model for angiogenesis. PMID:28332573

  2. [Controlling arachidonic acid metabolic network: from single- to multi-target inhibitors of key enzymes].

    PubMed

    Liu, Ying; Chen, Zheng; Shang, Er-chang; Yang, Kun; Wei, Deng-guo; Zhou, Lu; Jiang, Xiao-lu; He, Chong; Lai, Lu-hua

    2009-03-01

    Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.

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

    PubMed

    Zhang, Qian; Song, Taek Lyul

    2016-09-10

    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).

  4. Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods.

    PubMed

    Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J

    2017-03-03

    We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

  5. [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.

  6. 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

  7. A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

    PubMed

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

    2011-03-22

    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. 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. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by

  8. Design, synthesis and evaluation of seleno-dihydropyrimidinones as potential multi-targeted therapeutics for Alzheimer's disease.

    PubMed

    Canto, Rômulo F S; Barbosa, Flavio A R; Nascimento, Vanessa; de Oliveira, Aldo S; Brighente, Inês M C; Braga, Antonio Luiz

    2014-06-07

    In this paper we report the design, synthesis and evaluation of a series of seleno-dihydropyrimidinones as potential multi-targeted therapeutics for Alzheimer's disease. The compounds show excellent results as acetylcholinesterase inhibitors, being as active as the standard drug. All these compounds also show very good antioxidant activity through different mechanisms of action.

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

    PubMed

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    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. 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 fixed-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. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  10. 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

  11. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs.

    PubMed

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J; Fogel, Wieslawa A; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

  12. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    PubMed Central

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

  13. Antenna allocation in MIMO radar with widely separated antennas for multi-target detection.

    PubMed

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

    2014-10-27

    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.

  14. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

    PubMed Central

    Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

    2017-01-01

    The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

  15. ESAM: Endocrine inspired Sensor Activation Mechanism for multi-target tracking in WSNs

    NASA Astrophysics Data System (ADS)

    Adil Mahdi, Omar; Wahab, Ainuddin Wahid Abdul; Idris, Mohd Yamani Idna; Znaid, Ammar Abu; Khan, Suleman; Al-Mayouf, Yusor Rafid Bahar

    2016-10-01

    Target tracking is a significant application of wireless sensor networks (WSNs) in which deployment of self-organizing and energy efficient algorithms is required. The tracking accuracy increases as more sensor nodes are activated around the target but more energy is consumed. Thus, in this study, we focus on limiting the number of sensors by forming an ad-hoc network that operates autonomously. This will reduce the energy consumption and prolong the sensor network lifetime. In this paper, we propose a fully distributed algorithm, an Endocrine inspired Sensor Activation Mechanism for multi target-tracking (ESAM) which reflecting the properties of real life sensor activation system based on the information circulating principle in the endocrine system of the human body. Sensor nodes in our network are secreting different hormones according to certain rules. The hormone level enables the nodes to regulate an efficient sleep and wake up cycle of nodes to reduce the energy consumption. It is evident from the simulation results that the proposed ESAM in autonomous sensor network exhibits a stable performance without the need of commands from a central controller. Moreover, the proposed ESAM generates more efficient and persistent results as compared to other algorithms for tracking an invading object.

  16. 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.

  17. Collaborative multi-target tracking using networked micro-robotic vehicles

    NASA Astrophysics Data System (ADS)

    Biswas, Subir; Gupta, Sonny; Yu, Fan; Wu, Tao

    2007-04-01

    This paper presents a collaborative target tracking framework, in which distributed mechanisms are developed for tracking multiple mobile targets using a team of networked micro robotic vehicles. Applications of such a framework would include detection of multi-agent intrusion, network-assisted attack localization, and other collaborative search scenarios. The key idea of the developed framework is to design distributed algorithms that can be executed by tracking entities using a mobile ad hoc network. The paper comprises the following components. First, the software and hardware architectural detail of a Swarm Capable Autonomous Vehicle (SCAV) system that is used as the mobile platform in our target tracking application is presented. Second, the details of an indoor self-localization and Kalman filter based navigation system for the SCAV are presented. Third, a formal definition of the collaborative multi-target tracking problem and a heuristic based networked solution are developed. Finally, the performance of the proposed tracking framework is evaluated on a laboratory test-bed of a fleet of SCAV vehicles. A detailed system characterization in terms localization, navigation, and collaborative tracking performance is performed on the SCAV test-bed. In addition to valuable implementation insights about the localization, navigation, filtering, and ad hoc networking processes, a number of interesting conclusions about the overall tracking system are presented.

  18. Monoamino oxidase a: an interesting pharmacological target for the development of multi-target QSAR.

    PubMed

    Molina, Enrique; Sobarzo-Sanchez, Eduardo; Speck-Planche, Alejandro; Matos, Maria Joao; Uriarte, Eugenio; Santana, Lourdes; Yanez, Matilde; Orallo, Francisco

    2012-09-01

    With the significant increase of life expectancy of populations in societies today, the importance of the discovery of drugs associated with neurodegenerative diseases has emerged. Therefore, neurodegenerative diseases are an important topic in Medicinal Chemistry. Although drug discovery is considered a complex and slow process, new approaches and methods have been developed with the intention of finding new chemical entities in more efficient ways. This work provides a review of virtual methodologies applied in drug discovery and especially a new model for the prediction of MAO-A inhibitors using a multi-target QSAR methodology. This model involves a mixed approach containing simple descriptors based on atom-centered fragments and functional groups (DRAGON) and topological substructural molecular design descriptors (MODESLAB). This unified multi-species QSAR model was validated through a virtual screening of a new series of oxoisoaporphine derivatives, taking into account the information in the calculated fragmental contributions. Therefore, this method represents a useful tool for the in silico screening of MAO-A inhibitors.

  19. [STW 5/Iberogast: multi-target-action for treatment of functional dyspepsia and irritable bowel syndrome].

    PubMed

    Allescher, Hans-Dieter; Wagner, Hildebert

    2007-01-01

    Functional gastro-intestinal diseases such as functional dyspepsia and irritable bowel syndrome are a therapeutic challenge, as they are not only characterized by a multitude of symptoms, some of them with severe consequences for affected patients, but are also caused by a multitude of factors. The clinical efficacy of the therapeutics STW 5/Iberogast in these diseases has been proven in a number of randomized prospective clinical studies. Several preclinical studies suggest that its efficacy could be due to its complex composition of nine standardized herbal extracts, which act differently on multiple sites. This principle, which is quite popular in clinical medicine, was introduced as a multi-target therapy for functional bowel disorders. Components of STW 5/Iberogast reduce gastro-intestinal hypersensitivity and act spasmolytic on spastic, tonicising on atonic gastro-intestinal muscle. In addition a stimulating effect on reduced mucus-secretion, an inhibitory effect on enhanced gastric acid secretion and an anti-inflammatory effect have been shown. These effects could explain the clinical efficacy of STW5/Iberogast in a large range of symptoms.

  20. 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.

  1. 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

  2. Multi-Target Tracking Using an Improved Gaussian Mixture CPHD Filter

    PubMed Central

    Si, Weijian; Wang, Liwei; Qu, Zhiyu

    2016-01-01

    The cardinalized probability hypothesis density (CPHD) filter is an alternative approximation to the full multi-target Bayesian filter for tracking multiple targets. However, although the joint propagation of the posterior intensity and cardinality distribution in its recursion allows more reliable estimates of the target number than the PHD filter, the CPHD filter suffers from the spooky effect where there exists arbitrary PHD mass shifting in the presence of missed detections. To address this issue in the Gaussian mixture (GM) implementation of the CPHD filter, this paper presents an improved GM-CPHD filter, which incorporates a weight redistribution scheme into the filtering process to modify the updated weights of the Gaussian components when missed detections occur. In addition, an efficient gating strategy that can adaptively adjust the gate sizes according to the number of missed detections of each Gaussian component is also presented to further improve the computational efficiency of the proposed filter. Simulation results demonstrate that the proposed method offers favorable performance in terms of both estimation accuracy and robustness to clutter and detection uncertainty over the existing methods. PMID:27886106

  3. Vasculoprotection as a Convergent, Multi-Targeted Mechanism of Anti-AD Therapeutics and Interventions.

    PubMed

    Bhat, Narayan R

    2015-01-01

    Using a variety of animal models of Alzheimer's disease (AD), there have been a number of recent studies reporting varying degrees of success with anti-AD therapeutics. The efficacies are often discussed in terms of the modulatory effects of the compounds tested on identified or assumed targets among the known (or proposed) pathogenic and neuroprotective mechanisms, largely within the context of the dominant amyloid cascade hypothesis. However, it is clear that several of the relatively more efficacious treatments tend to be multifunctional and target multiple pathological processes associated with AD including most commonly, oxidative and metabolic stress and neuroinflammation. Increasing evidence suggests that vascular and neurodegenerative pathologies often co-exist and that neurovascular dysfunction plays a critical role in the development or progression of AD. In this review, we will discuss the significance of vasculoprotection or neurovascular unit integrity as a common, multi-targeted mechanism underlying the reported efficacy of a majority of anti-AD therapeutics--amyloid-targeted or otherwise--while providing a strong support for future neurovascular-based treatment strategies and interventions.

  4. 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

  5. Calibration Method for IATS and Application in Multi-Target Monitoring Using Coded Targets

    NASA Astrophysics Data System (ADS)

    Zhou, Yueyin; Wagner, Andreas; Wunderlich, Thomas; Wasmeier, Peter

    2017-06-01

    The technique of Image Assisted Total Stations (IATS) has been studied for over ten years and is composed of two major parts: one is the calibration procedure which combines the relationship between the camera system and the theodolite system; the other is the automatic target detection on the image by various methods of photogrammetry or computer vision. Several calibration methods have been developed, mostly using prototypes with an add-on camera rigidly mounted on the total station. However, these prototypes are not commercially available. This paper proposes a calibration method based on Leica MS50 which has two built-in cameras each with a resolution of 2560 × 1920 px: an overview camera and a telescope (on-axis) camera. Our work in this paper is based on the on-axis camera which uses the 30-times magnification of the telescope. The calibration consists of 7 parameters to estimate. We use coded targets, which are common tools in photogrammetry for orientation, to detect different targets in IATS images instead of prisms and traditional ATR functions. We test and verify the efficiency and stability of this monitoring method with multi-target.

  6. 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 shouldn’t 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 take live video imagery from multiple video cameras, identify individual moving targets from the background imagery, and then display 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 current capability.

  7. 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 shouldn't 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 take 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 current capability.

  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. A novel multi-target regression framework for time-series prediction of drug efficacy

    PubMed Central

    Li, Haiqing; Zhang, Wei; Chen, Ying; Guo, Yumeng; Li, Guo-Zheng; Zhu, Xiaoxin

    2017-01-01

    Excavating from small samples is a challenging pharmacokinetic problem, where statistical methods can be applied. Pharmacokinetic data is special due to the small samples of high dimensionality, which makes it difficult to adopt conventional methods to predict the efficacy of traditional Chinese medicine (TCM) prescription. The main purpose of our study is to obtain some knowledge of the correlation in TCM prescription. Here, a novel method named Multi-target Regression Framework to deal with the problem of efficacy prediction is proposed. We employ the correlation between the values of different time sequences and add predictive targets of previous time as features to predict the value of current time. Several experiments are conducted to test the validity of our method and the results of leave-one-out cross-validation clearly manifest the competitiveness of our framework. Compared with linear regression, artificial neural networks, and partial least squares, support vector regression combined with our framework demonstrates the best performance, and appears to be more suitable for this task. PMID:28098186

  10. 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

  11. Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics.

    PubMed

    Sarkar, Fazlul H; Li, Yiwei

    2009-11-01

    Cancer cells exhibit deregulation in multiple cellular signaling pathways. Therefore, treatments using specific agents that target only one pathway usually fail in cancer therapy. The combination treatments using chemotherapeutic agents with distinct molecular mechanisms are considered more promising for higher efficacy; however, using multiple agents contributes to added toxicity. Emerging evidence has shown that some "natural products" such as isoflavones, indole-3-carbinol (I3C) and its in vivo dimeric product 3,3'-diindolylmethane (DIM), and curcumin among many others, have growth inhibitory and apoptosis inducing effects on human and animal cancer cells mediated by targeting multiple cellular signaling pathways in vitro without causing unwanted toxicity in normal cells. Therefore, these non-toxic "natural products" from natural resources could be useful in combination with conventional chemotherapeutic agents for the treatment of human malignancies with lower toxicity and higher efficacy. In fact, recently increasing evidence from pre-clinical in vivo studies and clinical trials have shown some success in support of the use of rational design of multi-targeted therapies for the treatment of cancers using conventional chemotherapeutic agents in combination with "natural products". These studies have provided promising results and further opened-up newer avenues for cancer therapy. In this review article, we have succinctly summarized the known effects of "natural products" especially by focusing on isoflavones, indole-3-carbinol (I3C) and its in vivo dimeric product 3,3'-diindolylmethane (DIM), and curcumin, and provided a comprehensive view on the molecular mechanisms underlying the principle of cancer therapy using combination of "natural products" with conventional therapeutics.

  12. Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer's Disease.

    PubMed

    Rigacci, Stefania

    2015-01-01

    Amyloid diseases are characterized by the deposition of typically aggregated proteins/peptides in tissues, associated with degeneration and progressive functional impairment. Alzheimer's disease is one of the most studied neurodegenerative amyloid diseases and, in Western countries, a significant cause of dementia in the elderly. The so-called "Mediterranean diet" has been considered for long as the healthier dietary regimen, characterised by a great abundance in vegetables and fruits, extra virgin olive oil as the main source of fat, a moderate consumption of red wine and a reduced intake of proteins from red meat. Recent epidemiological studies support the efficacy of the Mediterranean diet not only against cardiovascular and cancer diseases (as previously demonstrated) but also against the cognitive decline associated with ageing, and several data are highlighting the role played by natural phenols, of which red wine and extra virgin olive oil are rich, in such context. In the meantime, studies conducted both in vivo and in vitro have started to reveal the great potential of the phenolic component of extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in counteracting amyloid aggregation and toxicity, with a particular emphasis on the pathways involved in the onset and progression of Alzheimer's disease: amyloid precursor protein processing, amyloid-beta (Aβ) peptide and tau aggregation, autophagy impairment, neuroinflammation. The aim of this review is to summarize the results of such research efforts, showing how the action of these phenols goes far beyond their renowned antioxidant activity and revealing their potential as multi-targeting agents against Alzheimer's disease.

  13. CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents.

    PubMed

    Yin, Lina; Hu, Qingzhong

    2014-01-01

    As the first in class steroid 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor, abiraterone acetate (of which the active metabolite is abiraterone) has been shown to improve overall survival in patients with castration-resistant prostate cancer (CRPC)--in those who are chemotherapy-naive and those previously treated with docetaxel. Furthermore, the clinical success of abiraterone demonstrated that CRPC, which has previously been regarded as an androgen-independent disease, is still driven, at least in part, by androgens. More importantly, abiraterone is a 'promiscuous' drug that interacts with a number of targets, which dictate its clinical benefits and adverse effects profile. Besides CYP17 inhibition, abiraterone acts as an antagonist to the androgen receptor and inhibits 3β-hydroxysteroid dehydrogenase--two effects that potentially contribute to its antitumour effects. However, the inhibition of the 17α-hydroxylase activity of CYP17, CYP11B1 and a panel of hepatic CYP enzymes leads to adverse effects and toxicities that include secondary mineralocorticoid excess. Abiraterone is also associated with increased incidence of cardiac disorders. Under such circumstances, development of new CYP17 inhibitors as an additional line of defence is urgently needed. To achieve enhanced clinical benefits, new strategies are being explored that include selective inhibition of the C17,20-lyase activity of CYP17 and multi-targeting strategies that affect androgen synthesis and signalling at different points. Some of these strategies-including the drugs orteronel, VT-464 and galeterone--are supported by preclinical data and are being explored in the clinic.

  14. Qingfei Xiaoyan Wan alleviates asthma through multi-target network regulation

    PubMed Central

    2013-01-01

    Background Qingfei Xiaoyan Wan (QFXY), a traditional Chinese formula, is widely used for relieving cough, asthma, upper respiratory tract infection, bronchitis, pneumonia, and etc. in clinic. Comparing with other anti-asthma drugs, it is characterised with moderate and persistent efficacy as well as few side effects, however, the underlying action mechanism still remains elusive. This study aimed to identify QFXY multi-target network regulation as an asthma controller. Methods This study established asthma model induced by histamine phosphate and acetylcholine chloride (His&Ach) in guinea pigs, which then were administered orally with QFXY. Hematoxylin-Eosin staining sections were applied for evaluating QFXY effect. In both Model and QFXY groups, customized microarrays and 2D electrophoresis were adopted to detect differentially expressed genes (diff genes) and proteins (diff proteins) respectively, and some diff proteins were identified with MALDI-TOF/MS. The checked diff genes and proteins underwent Cluster, GO and KEGG analysis. Based on GAD and HPRD databases, QFXY-asthma target regulation network was constructed. Results His&Ach-induced asthma model of guinea pigs was established. HE sections presented anti-inflammation and anti-remodelling effects of QFXY. Comparing with the Model group, 55 diff genes and 6 diff proteins were identified in QFXY group. Validation by qPCR and Western blot showed the microarray and 2D data reliable. Furthermore, QFXY-asthma target regulation network was achieved. Conclusions A primarily combined genomic and proteomic screening of QFXY targets displayed a series of candidate genes and proteins, which indicated that the effect of QFXY relied on the combined mechanism, anti-inflammation and anti-remodelling, as well as influencing signal transduction in vivo. PMID:23919426

  15. particles

    NASA Astrophysics Data System (ADS)

    Xia, Yu; Chen, Zhihong; Zhang, Zhengguo; Fang, Xiaoming; Liang, Guozheng

    2014-05-01

    We explore a facile and nontoxic hydrothermal route for synthesis of a Cu2ZnSnS4 nanocrystalline material by using l-cysteine as the sulfur source and ethylenediaminetetraacetic acid (EDTA) as the complexing agent. The effects of the amount of EDTA, the mole ratio of the three metal ions, and the hydrothermal temperature and time on the phase composition of the obtained product have been systematically investigated. The addition of EDTA and an excessive dose of ZnCl2 in the hydrothermal reaction system favor the generation of kesterite Cu2ZnSnS4. Pure kesterite Cu2ZnSnS4 has been synthesized at 180°C for 12 h from the reaction system containing 2 mmol of EDTA at 2:2:1 of Cu/Zn/Sn. It is confirmed by Raman spectroscopy that those binary and ternary phases are absent in the kesterite Cu2ZnSnS4 product. The kesterite Cu2ZnSnS4 material synthesized by the hydrothermal process consists of flower-like particles with 250 to 400 nm in size. It is revealed that the flower-like particles are assembled from single-crystal Cu2ZnSnS4 nanoflakes with ca. 20 nm in size. The band gap of the Cu2ZnSnS4 nanocrystalline material is estimated to be 1.55 eV. The films fabricated from the hierarchical Cu2ZnSnS4 particles exhibit fast photocurrent responses under intermittent visible-light irradiation, implying that they show potentials for use in solar cells and photocatalysis.

  16. 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.

  17. Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem

    NASA Astrophysics Data System (ADS)

    Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

    2016-12-01

    Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.

  18. A novel multi-target inhibitor harboring selectivity of inhibiting EGFR T790M sparing wild-type EGFR

    PubMed Central

    Song, Xiaoping; Qi, Xin; Wang, Qiang; Zhu, Weiming; Li, Jing

    2017-01-01

    Non-Small Cell Lung Cancer (NSCLC) is driven by a variety of deregulated kinases and the development of multi-target inhibitor for multiple signaling pathways or multiple steps is required. Here, we reported that ZWM026, an indolocarbazoles analogue, derived from mangrove in coastal marine wetland, exhibited selectivity and reversibility against T790M mutant over wild-type EGFR in naturally occurring NSCLC cells and constructed NIH-3T3 cells. It simultaneously inhibited activities of HER2, HER3, HER4 and RET but was different from current multi-target kinase inhibitors. There was no activity in protein kinase C (PKC) family which is generally recognized as molecule target of indolocarbazoles. ZWM026 had more potent activities against gefitinib sensitizing, non-sensitizing and rare EGFR mutant NSCLC cells and constructed NIH-3T3 cells. ZWM026 induced apoptosis and exerted a synergistic effect by combining with cisplatin in NCI-H1975 cells. In summary, we identified a novel reversible multi-target inhibitor which could serve as a promising lead compound of drug development for NSCLC. PMID:28979811

  19. A novel multi-target inhibitor harboring selectivity of inhibiting EGFR T790M sparing wild-type EGFR.

    PubMed

    Song, Xiaoping; Qi, Xin; Wang, Qiang; Zhu, Weiming; Li, Jing

    2017-01-01

    Non-Small Cell Lung Cancer (NSCLC) is driven by a variety of deregulated kinases and the development of multi-target inhibitor for multiple signaling pathways or multiple steps is required. Here, we reported that ZWM026, an indolocarbazoles analogue, derived from mangrove in coastal marine wetland, exhibited selectivity and reversibility against T790M mutant over wild-type EGFR in naturally occurring NSCLC cells and constructed NIH-3T3 cells. It simultaneously inhibited activities of HER2, HER3, HER4 and RET but was different from current multi-target kinase inhibitors. There was no activity in protein kinase C (PKC) family which is generally recognized as molecule target of indolocarbazoles. ZWM026 had more potent activities against gefitinib sensitizing, non-sensitizing and rare EGFR mutant NSCLC cells and constructed NIH-3T3 cells. ZWM026 induced apoptosis and exerted a synergistic effect by combining with cisplatin in NCI-H1975 cells. In summary, we identified a novel reversible multi-target inhibitor which could serve as a promising lead compound of drug development for NSCLC.

  20. Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem

    PubMed Central

    Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

    2016-01-01

    Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design. PMID:27958331

  1. Dual-action Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    PubMed

    Abdolmalekia, Azizeh; Ghasemi, Jahan B

    2016-09-27

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as a selective multi-target chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mt-drugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included.

  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. The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

    PubMed

    Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

    2016-01-01

    The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

  4. The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective

    PubMed Central

    Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

    2016-01-01

    The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology. PMID:27828998

  5. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    PubMed

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    diseases" remains a most pressing medical need. Currently, a change of paradigm can be observed with regard to a new interest in agents that modulate multiple targets simultaneously, essentially "dirty drugs." Targeting cellular function as a system rather than on the level of the single target, significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data. But the key is the extraction of relevant molecular information from biological systems by implementing rigid statistical procedures to differential proteomic analytics.

  6. 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

  7. Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods.

    PubMed

    Abdolmaleki, Azizeh; Ghasemi, Jahan B; Ghasemi, Fatemeh

    2017-01-01

    Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 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.

  9. Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317.

    PubMed

    Toyama, Hirozumi; Sato, Shoko; Shirakawa, Hitoshi; Komai, Michio; Hashimoto, Yuichi; Fujii, Shinya

    2016-04-01

    We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative 6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5). Compound 6 showed intermediate hydrophobicity between the corresponding alcohol 13 and perfluoroalcohol 5. While 5 exhibited potent activities toward liver X receptor α and β, farnesoid X receptor, pregnane X receptor (PXR) and retinoic acid receptor-related orphan receptor (ROR)γ, silanol 6 exhibited activity only toward PXR and RORs. Incorporation of silanol instead of perfluoroalcohol is a promising option for developing novel target-selective, biologically active compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Near-infrared reflection from Al-doped ZnO films prepared by multi-target reactive sputtering

    NASA Astrophysics Data System (ADS)

    Okuhara, Y.; Matsubara, H.; Takata, M.

    2011-10-01

    Thin films of aluminium-doped zinc oxide (ZnO:Al) as heat reflective coatings were prepared by multi-target reactive sputtering using metallic Zn and Al targets. An optimization of Al content and a reduction in oxygen partial pressure were crucial in increasing the carrier concentration Ne and the Hall mobility μ. The ZnO:Al film with the highest Ne achieved the shortest plasma wavelength λp of 1375 nm, which shifted the near-infrared reflectance spectrum closer to the visible region. The high μ reduced the optical absorption and enhanced the reflectance. Moreover, the multi-target system enabled intermittent doping of Al, which was applied to stack multilayers consisting of non-doped and Al-doped ZnO layers. A drop in the refractive indices n above λp for the ZnO:Al layers formed the periodic distribution of n in the thickness direction, which provided a high reflectance zone from 1000 to 1400 nm in wavelength.

  12. Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer's disease.

    PubMed

    Barbosa, Flavio A R; Canto, Rômulo F S; Saba, Sumbal; Rafique, Jamal; Braga, Antonio L

    2016-11-15

    This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer's disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity. In addition, they showed acetylcholinesterase inhibition activity and some of them presented activity superior to that of the standard drug galantamine. The in silico predictions showed that the compound 1h may present a good pharmacokinetic profile. Therefore, the series of DHPM-derived selenoesters described herein displayed good potential for the development of antioxidant and anticholinesterasic agents in the search for new multi-targeted therapeutics for the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 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

  14. 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.

  15. Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.

    PubMed

    Rizzo, Stefano; Bisi, Alessandra; Bartolini, Manuela; Mancini, Francesca; Belluti, Federica; Gobbi, Silvia; Andrisano, Vincenza; Rampa, Angela

    2011-09-01

    The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the development of a broad collection of very interesting homo- and heterodimeric structures, conceived in light of the emerging multi-target approach for AD-related drug discovery. As a contribution to the topic, we report here the design, synthesis and biological evaluation of 12 compounds referable to bis(7)-tacrine. In addition to the cholinesterase activity, some of the selected compounds (7-9 and 12) were capable of inhibiting the non-enzymatic function of AChE and/or showed a remarkable activity against BACE1. Thus, the present study outlines a series of newly synthesized molecules, structurally related to bis(7)-tacrine, endowed with extended biological profile in agreement with the emerging multi-target paradigm.

  16. One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

    PubMed Central

    Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

    2017-01-01

    Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

  17. 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

  18. 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

  19. Tracking the Turn Maneuvering Target Using the Multi-Target Bayes Filter with an Adaptive Estimation of Turn Rate.

    PubMed

    Liu, Zong-Xiang; Wu, De-Hui; Xie, Wei-Xin; Li, Liang-Qun

    2017-02-15

    Tracking the target that maneuvers at a variable turn rate is a challenging problem. The traditional solution for this problem is the use of the switching multiple models technique, which includes several dynamic models with different turn rates for matching the motion mode of the target at each point in time. However, the actual motion mode of a target at any time may be different from all of the dynamic models, because these models are usually limited. To address this problem, we establish a formula for estimating the turn rate of a maneuvering target. By applying the estimation method of the turn rate to the multi-target Bayes (MB) filter, we develop a MB filter with an adaptive estimation of the turn rate, in order to track multiple maneuvering targets. Simulation results indicate that the MB filter with an adaptive estimation of the turn rate, is better than the existing filter at tracking the target that maneuvers at a variable turn rate.

  20. Promise of Neurorestoration and Mitochondrial Biogenesis in Parkinson's Disease with Multi Target Drugs: An Alternative to Stem Cell Therapy

    PubMed Central

    Oh, Young J.

    2013-01-01

    There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis. PMID:24167412

  1. The synthesis of Zr-Nb-N nanocomposite coating prepared by multi-target magnetron co-sputtering

    NASA Astrophysics Data System (ADS)

    Zhang, S.; Wang, N.; Li, D. J.; Dong, L.; Gu, H. Q.; Wan, R. X.; Sun, X.

    2013-07-01

    Growth, structure, and mechanical properties of the nanocomposite Zr-Nb-N coatings deposited on Si(1 0 0) at different substrate bias voltages and substrate temperatures were performed by multi-target magnetron co-sputtering system. Extensive measurements were taken to investigate the influences of substrate bias voltage and deposition temperature on microstructure, hardness, elastic modulus, residual stress, critical fracture load. The maximum hardness and elastic modulus was up to 36 GPa and 425 GPa, respectively. The hardest coating also showed the lowest residual stress and the highest critical load. These enhancement effects should be related to nanocrystalline solid-solution microstructure formation and smaller grain size. These Zr-Nb-N coatings appeared to be a promising composite coating system suitable for engineering applications.

  2. 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.

  3. SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models.

    PubMed

    Jiang, Xi-Fei; Dai, Yang; Peng, Xia; Shen, Yan-Yan; Su, Yi; Wei, Man-Man; Liu, Wei-Ren; Ding, Zhen-Bin; Zhang, Ao; Shi, Ying-Hong; Ai, Jing

    2017-09-14

    Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies, especially those lacking effective treatments. SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor. Here, we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo. Among a panel of 20 tyrosine kinases screened, SOMCL-085 potently inhibited FGFR1, FGFR2 and FGFR3 kinase activity, with IC50 values of 1.8, 1.9 and 6.9 nmol/L, respectively. This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR, but without obvious inhibitory effect on other 12 tyrosine kinases. In 3 representative human cancer cell lines with different mechanisms of FGFR activation tested, SOMCL-085 (20-500 nmol/L) dose-dependently inhibited FGFR1-3 phosphorylation and the phosphorylation of their key downstream effectors PLCγ and Erk. In 7 FGFR aberrant human cancer cell lines, regardless of the mechanistic complexity of FGFR over-activation, SOMCL-085 potently inhibited FGFR-driven cell proliferation by arresting cells at the G1/S phase. In the FGFR1-amplified lung cancer cell line H1581 xenograft mice and FGFR2-amplified gastric cancer cell line SNU16 xenograft mice, oral administration of SOMCL-085 (25, 50 mg·kg(-1)·d(-1)) for 21 days substantially suppressed tumor growth without affecting their body-weight. These results suggest that SOMCL-085 is a potent multi-target FGFR inhibitor that inhibits the FGFR-dependent neoplastic phenotypes of human cancer cells in vitro and in vivo.

  4. 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

    2016-10-04

    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.

  5. Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature.

    PubMed

    Poornima, Paramasivan; Kumar, Jothi Dinesh; Zhao, Qiaoli; Blunder, Martina; Efferth, Thomas

    2016-09-01

    Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and due to lower side effects. In this review, we discuss the application of network pharmacology for cancer drug discovery. We provide an overview of the current state of knowledge on network pharmacology, focus on different technical approaches and implications for cancer therapy (e.g. polypharmacology and synthetic lethality), and illustrate the therapeutic potential with selected examples green tea polyphenolics, Eleutherococcus senticosus, Rhodiola rosea, and Schisandra chinensis). Finally, we present future perspectives on their plausible applications for diagnosis and therapy of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

    PubMed Central

    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

  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 .

  8. 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

  9. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.

    PubMed

    Herranz-López, María; Olivares-Vicente, Mariló; Encinar, José Antonio; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

    2017-08-20

    Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity.

  10. 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.

  11. Multi-target interphase fluorescence in situ hybridization assay increases sensitivity of sputum cytology as a predictor of lung cancer.

    PubMed

    Varella-Garcia, Marileila; Kittelson, John; Schulte, Aline P; Vu, Kieu O; Wolf, Holly J; Zeng, Chan; Hirsch, Fred R; Byers, Tim; Kennedy, Tim; Miller, York E; Keith, Robert L; Franklin, Wilbur A

    2004-01-01

    Survival rates for lung cancer are low because patients have disseminated disease at diagnosis; therefore tests for early diagnosis are highly desirable. This pilot study investigated occurrence of chromosomal aneusomy in sputum from a 33 case-control cohort matched on age, gender, and date of sample collection. Subjects had chronic obstructive pulmonary disease and > or = 30 pack-years of tobacco use, and aneusomy was tested using a multi-target DNA FISH assay (LAVysion, Abbott/Vysis). In specimens collected within 12 months of lung cancer diagnosis, abnormality was more frequent among the 18 cases (41%) than the 17 controls (6%; P = 0.04). Aneusomy had no significant association with cytologic atypia, which might indicate that molecular and morphological changes could be independent markers of tumorigenesis. Combining both tests, abnormality was found in 83% of the cases and 20% of the controls (P = 0.0004) suggesting that FISH may improve the sensitivity of cytologic atypia as a predictor of lung cancer.

  12. 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

    2016-01-28

    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.

  13. Sample Preparation Strategies for the Effective Quantitation of Hydrophilic Metabolites in Serum by Multi-Targeted HILIC-MS/MS.

    PubMed

    Tsakelidou, Elisavet; Virgiliou, Christina; Valianou, Lemonia; Gika, Helen G; Raikos, Nikolaos; Theodoridis, Georgios

    2017-03-30

    The effect of endogenous interferences of serum in multi-targeted metabolite profiling HILIC-MS/MS analysis was investigated by studying different sample preparation procedures. A modified QuEChERS dispersive SPE protocol, a HybridSPE protocol, and a combination of liquid extraction with protein precipitation were compared to a simple protein precipitation. Evaluation of extraction efficiency and sample clean-up was performed for all methods. SPE sorbent materials tested were found to retain hydrophilic analytes together with endogenous interferences, thus additional elution steps were needed. Liquid extraction was not shown to minimise matrix effects. In general, it was observed that a balance should be reached in terms of recovery, efficient clean-up, and sample treatment time when a wide range of metabolites are analysed. A quick step for removing phospholipids prior to the determination of hydrophilic endogenous metabolites is required, however, based on the results from the applied methods, further studies are needed to achieve high recoveries for all metabolites.

  14. Ilizarov treatment of congenital pseudarthrosis of the tibia: a multi-targeted approach using the Ilizarov technique.

    PubMed

    Choi, In Ho; Cho, Tae-Joon; Moon, Hyuk Ju

    2011-03-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. An Ab Initio Method for Designing Multi-Target Specific Pharmacophores using Complementary Interaction Field of Aspartic Proteases.

    PubMed

    Kaalia, Rama; Kumar, Amit; Srinivasan, Ashwin; Ghosh, Indira

    2015-06-01

    For past few decades, key objectives of rational drug discovery have been the designing of specific and selective ligands for target proteins. Infectious diseases like malaria are continuously becoming resistant to traditional medicines, which inculcates need for new approaches to design inhibitors for antimalarial targets. A novel method for ab initio designing of multi target specific pharmacophores using the interaction field maps of active sites of multiple proteins has been developed to design 'specificity' pharmacophores for aspartic proteases. The molecular interaction field grid maps of active sites of aspartic proteases (plasmepsin II & IV from Plasmodium falciparum, plasmepsin from Plasmodium vivax, pepsin & cathepsin D from human) are calculated and common pharmacophoric features for favourable binding spots in active sites are extracted in the form of cliques of graphs using inductive logic programming (ILP). The two pharmacophore ensembles are constructed from largest common cliques by imposing size of receptor active site (L) and domain-specific receptor-ligand information (S). The overlap of chemical space between two ensembles and the results of virtual screening of inhibitor database with known activities show that this method can design efficient pharmacophores with no prior ligand information. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Multi-target QPDR classification model for human breast and colon cancer-related proteins using star graph topological indices.

    PubMed

    Munteanu, Cristian Robert; Magalhães, Alexandre L; Uriarte, Eugenio; González-Díaz, Humberto

    2009-03-21

    The cancer diagnostic is a complex process and, sometimes, the specific markers can interfere or produce negative results. Thus, new simple and fast theoretical models are required. One option is the complex network graphs theory that permits us to describe any real system, from the small molecules to the complex genetic, neural or social networks by transforming real properties in topological indices. This work converts the protein primary structure data in specific Randic's star networks topological indices using the new sequence to star networks (S2SNet) application. A set of 1054 proteins were selected from previous works and contains proteins related or not with two types of cancer, human breast cancer (HBC) and human colon cancer (HCC). The general discriminant analysis method generates an input-coded multi-target classification model with the training/predicting set accuracies of 90.0% for the forward stepwise model type. In addition, a protein subset was modified by single amino acid mutations with higher log-odds PAM250 values and tested with the new classification if can be related with HBC or HCC. In conclusion, we shown that, using simple input data such is the primary protein sequence and the simples linear analysis, it is possible to obtain accurate classification models that can predict if a new protein related with two types of cancer. These results promote the use of the S2SNet in clinical proteomics.

  18. Comprehensive insight into the binding of sunitinib, a multi-targeted anticancer drug to human serum albumin

    NASA Astrophysics Data System (ADS)

    Kabir, Md. Zahirul; Tee, Wei-Ven; Mohamad, Saharuddin B.; Alias, Zazali; Tayyab, Saad

    2017-06-01

    Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04 × 104 M-1), obtained at 298 K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.

  19. Tracking the Turn Maneuvering Target Using the Multi-Target Bayes Filter with an Adaptive Estimation of Turn Rate

    PubMed Central

    Liu, Zong-xiang; Wu, De-hui; Xie, Wei-xin; Li, Liang-qun

    2017-01-01

    Tracking the target that maneuvers at a variable turn rate is a challenging problem. The traditional solution for this problem is the use of the switching multiple models technique, which includes several dynamic models with different turn rates for matching the motion mode of the target at each point in time. However, the actual motion mode of a target at any time may be different from all of the dynamic models, because these models are usually limited. To address this problem, we establish a formula for estimating the turn rate of a maneuvering target. By applying the estimation method of the turn rate to the multi-target Bayes (MB) filter, we develop a MB filter with an adaptive estimation of the turn rate, in order to track multiple maneuvering targets. Simulation results indicate that the MB filter with an adaptive estimation of the turn rate, is better than the existing filter at tracking the target that maneuvers at a variable turn rate. PMID:28212291

  20. A multi-target real-time PCR assay for rapid identification of meningitis-associated microorganisms.

    PubMed

    Favaro, Marco; Savini, Vincenzo; Favalli, Cartesio; Fontana, Carla

    2013-01-01

    A central nervous system (CNS) infection, such as meningitis, is a serious and life-threatening condition. Bacterial meningitis can be severe and may result in brain damage, disability or even death. Rapid diagnosis of CNS infections and identification of the pathogenic microorganisms are needed to improve the patient outcome. Bacterial culture of a patient's cerebrospinal fluid (CSF) is currently considered the "gold standard" for diagnosing bacterial meningitis. From the CSF cultures researchers can assess the in vitro susceptibility of the causative microorganism to determine the best antibiotic treatment. However, many of the culture assays, such as microscopy and the latex agglutination test are not sensitive. To enhance pathogen detection in CSF samples we developed a multi-target real-time PCR assay that can rapidly identify six different microorganisms: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Streptococcus agalactiae, Listeria monocytogenes and Cryptococcus neoformans. In this study we applied this PCR analysis to 296 CSF samples from patients who were suspected of having meningitis. Of the 296 samples that were examined, 59 samples were positive according to the CSF culture and/or molecular assays. Forty-six CSF samples were positive for both the CSF culture and our real-time PCR assay, while 13 samples were positive for the real-time PCR but negative for the traditional assays. This discrepancy may have been caused by the fact that these samples were collected from 23 patients who were treated with antimicrobials before CSF sampling.

  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. 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

    2013-06-28

    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.

  3. Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To-Date Evidence-Based Review.

    PubMed

    Sunil, Dhanya; Kamath, Pooja R

    2017-01-01

    Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm "one-compound-one-target" has failed and subsequently shifted to two-drug cocktail and recently the "multi-target approach" in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed.

  4. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

    PubMed Central

    Herranz-López, María; Olivares-Vicente, Mariló; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

    2017-01-01

    Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. PMID:28825642

  5. One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke.

    PubMed

    Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

    2017-01-01

    Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA&#039;s therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and bloodbrain- barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds&#039; studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.

  6. An overview on natural cholinesterase inhibitors--a multi-targeted drug class--and their mass production.

    PubMed

    Orhan, I Erdogan; Orhan, G; Gurkas, E

    2011-09-01

    Cholinesterase enzyme family consisting of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) is important in pathogenesis of Alzheimer's disease (AD), explained by "cholinergic hypothesis". Accordingly, deficiency of the neuromediator called "acetylcholine" excessive amount of BChE has been well-described in the brains of AD patients. Consequently, cholinesterase inhibition has become one of the most-prescribed treatment strategies for AD. In fact, cholinesterase inhibitors have been also reported for their effectiveness in some other diseases including glaucoma, myasthenia gravies, as well as Down syndrome, lately. They play a role in the action of mechanism of insecticidal drugs such as carbamate derivatives as well as nerve gases such as malathion and parathion. All these utilizations can make them a multi-targeted drug class putting a special emphasis on AD therapy in the first place. Several inhibitors of cholinesterases with synthetic and natural origins are available in drug market; however, the reasons including side effects, relatively low bioavailability, etc. limit their uses in medicine and there is still a great demand to discover new cholinesterase inhibitors. Galanthamine, an alkaloid derivative isolated from snowdrop (Galanthus nivalis L.), is the latest anticholinesterase drug used against AD. Huperzine A, isolated from Huperzia serrata (Thunb.) Trev. is the most-promising drug candidate with potent anticholinesterase effect and it is a licensed anti-AD drug in China. In this review, a short introduction will be given on known cholinesterase inhibitors and, then, galanthamine and huperzine A will be covered in regard with their cholinesterase inhibitory potentials and mass productions by organic synthesis and in vitro culture techniques.

  7. Dual inhibitors of β-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates.

    PubMed

    Viayna, Elisabet; Sabate, Raimon; Muñoz-Torrero, Diego

    2013-01-01

    Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer's disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multitarget anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

  8. Multi-Target Approaches in Colon Cancer Chemoprevention Based on Systems Biology of Tumor Cell-Signaling

    PubMed Central

    Guruswamy, Suresh; Rao, Chinthalapally V.

    2008-01-01

    Colorectal cancer is the leading cause of cancer related deaths in the United States. Although it is preventable, thousands of lives are lost each year in the U.S. to colorectal cancer than to breast cancer and AIDS combined. In colon cancer, the formation and progression of precancerous lesions like aberrant crypt foci and polyps is associated with the up-regulation of cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and hydroxy methyl glutaryl CoA reductase (HMG-CoA reductase). The current review will focus on the signaling pathway involving COX-2 and HMG-CoA reductase enzymes and their downstream effectors in signaling mechanism. Cancer cells need huge pools of both cholesterol and isoprenoids to sustain their unlimited growth potential. Cholesterol by modulating caveolae formation regulates several signaling molecules like AKT, IGFR, EGFR and Rho which are involved in cell growth and survival. Cholesterol is also essential for lipid body formation which serves as storage sites for COX-2, eicosanoids and caveolin-1. Experimental studies have identified important mechanisms showing that COX-2, caveolin-1, lipid bodies and prenylated proteins is involved in carcinogenesis. Therefore multi-target, multi-drug approach is the ideal choice for effective colon cancer chemoprevention. This review will give an overview of the two pathways, their signaling networks, and the interactions between the components of the two networks in the activation and regulation of cell signaling involving growth/survival and explain the rationale for colon cancer chemoprevention using COX-2 inhibitors and statins. PMID:19763245

  9. AChE Inhibition-based Multi-target-directed Ligands, a Novel Pharmacological Approach for the Symptomatic and Disease-modifying Therapy of Alzheimer's Disease

    PubMed Central

    Wang, Yu; Wang, Hao; Chen, Hong-zhuan

    2016-01-01

    Alzheimer's disease (AD) is the most common form of dementia in elder people, characterised by a progressive decline in memory as a result of an impairment of cholinergic neurotransmission. To date acetylcholinesterase inhibitors (AChEIs) have become the most prescribed drugs for the symptomatic treatment of mild to moderate AD. However, the traditional “one molecule-one target” paradigm is not sufficient and appropriate to yield the desired therapeutic efficacy since multiple factors, such as amyloid-β (Aβ) deposits, neuroinflammation, oxidative stress, and decreased levels of acetylcholine (ACh) have been thought to play significant roles in the AD pathogenesis. New generation of multi-target drugs is earnestly demanded not only for ameliorating symptoms but also for modifying the disease. Herein, we delineated the catalytic and non-catalytic functions of AChE, and summarized the works of our group and others in research and development of novel AChEI-based multi-target-directed ligands (MTDLs), such as dual binding site AChEIs and multi-target AChEIs inhibiting Aβ aggregation, regulating Aβ procession, antagonizing platelet-activating factor (PAF) receptor, scavenging oxygen radical, chelating metal ions, inhibiting monoamine oxidase B (MAO-B), blocking N-methyl-D-aspartic acid (NMDA) receptor and others. PMID:26786145

  10. Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I.

    PubMed

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anti- cancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets, for anticancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. The result is the rapid discovery of new anticancer drugs. In this article we discuss the application of molecular modeling, molecular docking and virtual high-throughput screening to multi-targeted anticancer drug discovery. Efforts have been made to employ in silico methods for facilitating the search and design of selective multi-target agents. These computer aided molecular design methods have shown promising potential in facilitating drug discovery directed at selective multiple targets and is expected to contribute to intelligent lead anticancer drugs.

  11. Particle flow superpositional GLMB filter

    NASA Astrophysics Data System (ADS)

    Saucan, Augustin-Alexandru; Li, Yunpeng; Coates, Mark

    2017-05-01

    In this paper we propose a Superpositional Marginalized δ-GLMB (SMδ-GLMB) filter for multi-target tracking and we provide bootstrap and particle flow particle filter implementations. Particle filter implementations of the marginalized δ-GLMB filter are computationally demanding. As a first contribution we show that for the specific case of superpositional observation models, a reduced complexity update step can be achieved by employing a superpositional change of variables. The resulting SMδ-GLMB filter can be readily implemented using the unscented Kalman filter or particle filtering methods. As a second contribution, we employ particle flow to produce a measurement-driven importance distribution that serves as a proposal in the SMδ-GLMB particle filter. In high-dimensional state systems or for highly- informative observations the generic particle filter often suffers from weight degeneracy or otherwise requires a prohibitively large number of particles. Particle flow avoids particle weight degeneracy by guiding particles to regions where the posterior is significant. Numerical simulations showcase the reduced complexity and improved performance of the bootstrap SMδ-GLMB filter with respect to the bootstrap Mδ-GLMB filter. The particle flow SMδ-GLMB filter further improves the accuracy of track estimates for highly informative measurements.

  12. Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug

    PubMed Central

    Zimmermann, Grant R; Avery, William; Finelli, Alyce L; Farwell, Melissa; Fraser, Christopher C; Borisy, Alexis A

    2009-01-01

    observed in the cellular network of corticotroph AtT-20/D16v-F2 cells in vitro, as measured by pro-opiomelanocortin expression and adrenocorticotropic hormone secretion. Conclusions These data suggest that the multi-target mechanism of low-dose prednisolone and dipyridamole creates a dissociated activity profile with an increased therapeutic window through cellular network selective amplification of glucocorticoid-mediated anti-inflammatory signaling. PMID:19171052

  13. Simulation Research Framework with Embedded Intelligent Algorithms for Analysis of Multi-Target, Multi-Sensor, High-Cluttered Environments

    NASA Astrophysics Data System (ADS)

    Hanlon, Nicholas P.

    nearly identical performance metrics at orders of magnitude faster in execution. Second, a fuzzy inference system is presented that alleviates air traffic controllers from information overload by utilizing flight plan data and radar/GPS correlation values to highlight aircraft that deviate from their intended routes. Third, a genetic algorithm optimizes sensor placement that is robust and capable of handling unexpected routes in the environment. Fourth, a fuzzy CUSUM algorithm more accurately detects and corrects aircraft mode changes. Finally, all the work is packaged in a holistic simulation research framework that provides evaluation and analysis of various multi-sensor, multi-target scenarios.

  14. Amelioration of Danhong injection on the lipopolysaccharide-stimulated systemic acute inflammatory reaction via multi-target strategy.

    PubMed

    Gao, Li-Na; Cui, Yuan-Lu; Wang, Qiang-Song; Wang, Shao-Xia

    2013-10-07

    coincidence with the result of Proteome profile array. Meanwhile, the mRNA expressions of iNOS, IL-6, IL-1β, MCP-1 in mice liver and kidney were significantly reduced by DHI. Experiments performed in vitro further revealed that the productions of NO, PGE2 and the mRNA expressions of iNOS, COX-2 were notably inhibited by DHI. Cell-based ELISA revealed that the COX-2 protein expression was diminished by DHI. The results of ELISA demonstrated that DHI significantly down-regulated the protein productions of IL-6 and MCP-1. Furthermore, the mRNA expressions of iNOS, COX-2, TNF-α, IL-1β, IL-6 and MCP-1 analyzed by real-time RT-PCR were suppressed by DHI. These results demonstrate that DHI exerts the protective effect through inhibiting the expressions of iNOS, COX-2, IL-1β, IL-6, MCP-1 and TNF-α, which elucidate that DHI may be a strongly multi-target Chinese medicine injection on improving the inflammatory diseases. © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. A Network-Based Data Integration Approach to Support Drug Repurposing and Multi-Target Therapies in Triple Negative Breast Cancer

    PubMed Central

    Cohen, Laurie D.; Demartini, Andrea; Amato, Angela; Eterno, Vincenzo; Zambelli, Alberto; Bellazzi, Riccardo

    2016-01-01

    The integration of data and knowledge from heterogeneous sources can be a key success factor in drug design, drug repurposing and multi-target therapies. In this context, biological networks provide a useful instrument to highlight the relationships and to model the phenomena underlying therapeutic action in cancer. In our work, we applied network-based modeling within a novel bioinformatics pipeline to identify promising multi-target drugs. Given a certain tumor type/subtype, we derive a disease-specific Protein-Protein Interaction (PPI) network by combining different data-bases and knowledge repositories. Next, the application of suitable graph-based algorithms allows selecting a set of potentially interesting combinations of drug targets. A list of drug candidates is then extracted by applying a recent data fusion approach based on matrix tri-factorization. Available knowledge about selected drugs mechanisms of action is finally exploited to identify the most promising candidates for planning in vitro studies. We applied this approach to the case of Triple Negative Breast Cancer (TNBC), a subtype of breast cancer whose biology is poorly understood and that lacks of specific molecular targets. Our “in-silico” findings have been confirmed by a number of in vitro experiments, whose results demonstrated the ability of the method to select candidates for drug repurposing. PMID:27632168

  16. 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

  17. A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer's Disease Transgenic Mice by Inhibiting Aβ Aggregation and Blocking the RAGE/Aβ Axis.

    PubMed

    Cui, Lili; Cai, Yujie; Cheng, Wanwen; Liu, Gen; Zhao, Jianghao; Cao, Hao; Tao, Hua; Wang, Yan; Yin, Mingkang; Liu, Tingting; Liu, Yu; Huang, Pengru; Liu, Zhou; Li, Keshen; Zhao, Bin

    2017-04-01

    The treatment of AD is a topic that has puzzled researchers for many years. Current mainstream theories still consider Aβ to be the most important target for the cure of AD. In this study, we attempted to explore multiple targets for AD treatments with the aim of identifying a qualified compound that could both inhibit the aggregation of Aβ and block the RAGE/Aβ axis. We believed that a compound that targets both Aβ and RAGE may be a feasible strategy for AD treatment. A novel and small natural compound, Matrine (Mat), was identified by high-throughput screening of the main components of traditional Chinese herbs used to treat dementia. Various experimental techniques were used to evaluate the effect of Mat on these two targets both in vitro and in AD mouse model. Mat could inhibit Aβ42-induced cytotoxicity and suppress the Aβ/RAGE signaling pathway in vitro. Additionally, the results of in vivo evaluations of the effects of Mat on the two targets were consistent with the results of our in vitro studies. Furthermore, Mat reduced proinflammatory cytokines and Aβ deposition and attenuated the memory deficits of AD transgenic mice. We believe that this novel, multi-target strategy to inhibit both Aβ and RAGE, is worthy of further exploration. Therefore, our future studies will focus on identifying even more effective multi-target compounds for the treatment of AD based on the molecular structure of Mat.

  18. Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II.

    PubMed

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anticancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. In this part II we will review the role and methodology of ligand-, structure- and fragment-based computer-aided drug design computer aided drug desing (CADD), virtual high throughput screening (vHTS), de novo drug design, fragment-based design and structure-based molecular docking, homology modeling, combinatorial chemistry and library design, pharmacophore model chemistry and informatics in modern drug discovery.

  19. High Frequency of Genetic Alterations in Non-small Cell Lung Cancer Detected by Multi-target Fluorescence In Situ Hybridization

    PubMed Central

    Kang, Ji Un; Kwon, Kye Chul; Park, Jong Woo; Shin, So Youn; Kim, Jin Man; Jung, Sung Su

    2007-01-01

    Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer. PMID:17923754

  20. High frequency of genetic alterations in non-small cell lung cancer detected by multi-target fluorescence in situ hybridization.

    PubMed

    Kang, Ji Un; Koo, Sun Hoe; Kwon, Kye Chul; Park, Jong Woo; Shin, So Youn; Kim, Jin Man; Jung, Sung Su

    2007-09-01

    Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer.

  1. The Multi-Target Drug M30 Shows Pro-Cognitive and Anti-Inflammatory Effects in a Rat Model of Alzheimer's Disease.

    PubMed

    Pimentel, Luisa S; Allard, Simon; Do Carmo, Sonia; Weinreb, Orly; Danik, Marc; Hanzel, Cecilia E; Youdim, Moussa B; Cuello, A Claudio

    2015-01-01

    Current therapies for Alzheimer's disease (AD) offer partial symptomatic relief and do not modify disease progression. There is substantial evidence indicating a disease onset years before clinical diagnosis, at which point no effective therapy has been found. In this study, we investigated the efficacy of a new multi-target drug, M30, at relatively early stages of the AD-like amyloid pathology in a robust rat transgenic model. McGill-R-Thy1-APP transgenic rats develop the full AD-like amyloid pathology in a progressive fashion, and have a minimal genetic burden. McGill rats were given 5 mg/kg M30 or vehicle per os, every 2 days for 4 months, starting at a stage where the transgenic animals suffer detectable cognitive impairments. At the completion of the treatment, cognitive functions were assessed with Novel Object Location and Novel Object Recognition tests. The brains were then analyzed to assess amyloid-β (Aβ) burden and the levels of key inflammatory markers. Long-term treatment with M30 was associated with both the prevention and the reversal of transgene-related cognitive decline. The effects on cognition were accompanied by a shift of the Aβ-immunoreactive material toward an amyloid plaque aggregated molecular form, diminished molecular signs of CNS inflammation and a change in microglia morphology toward a surveying phenotype. This study is the first to demonstrate the therapeutic potential of M30 in a rat model of the AD amyloid pathology. It provides a rationale for further investigations with M30 and with potential multi-target approaches to delay, prevent or reverse the progression the AD pathology at early disease-stages.

  2. Market-Driven Multi-Robot Exploration

    DTIC Science & Technology

    2002-01-01

    Rekleitis et. al. [5] proposed another method of cooperation in which stationary robots visually track moving robots as they sweep across the camera...useless. The methods of Rekleitis et. al. [5] and Latimer et. al. [4] have the disadvantage of keeping the robots in close proximity and require...based coverage with robot teams. In Proceedings of the International Conference on Robotics and Automation. IEEE, 2002. [5] I. M. Rekleitis , G. Dudek

  3. 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.

  4. ROBODEXS; Multi-robot Deployment & Extraction System

    DTIC Science & Technology

    2012-04-03

    Deployment & Extraction System (ROBODEXS) is a result of our development research to improve marsupial robotic deployment at safe standoff distances. The...Keywords: ROBODEXS, Marsupial , Deployment, Extraction, Multiple UGV, Modular, Scalable, Robot, Unmanned 1. INTRODUCTION Until recently, small...down to the ground level for deployment.. Research has shown commercial robotics developers have also experimented with marsupial capabilities, allowing

  5. Commanding Heterogeneous Multi-Robot Teams

    DTIC Science & Technology

    2014-06-01

    Language (BML) Battle Management Language (BML) is an artificial , unambiguous, human-readable language and open standard that has originally been...2005. [2] T.N. Dupuy, A Genius for War: The German Army and General Staff, 1807-1945. Englewood Cliffs, NJ: Prentice-Hall, 1977. [3] B. Gautreau

  6. A Hybrid Multi-Robot Control Architecture

    DTIC Science & Technology

    2007-12-01

    Applications of Artificial Intelligence , 19:179–188, 2006. 14. Cao, Y. Uny, Alex S. Fukunaga, and Andrew B. Kahng. “Cooperative Mobile Robotics...13. Camacho, David, Fernando Fernández, and Miguel A. Rodelgo. “Roboskeleton: An architecture for coordinating robot soccer agents”. Engineering

  7. 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. © 2013.

  8. 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

  9. 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

    2015-03-06

    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.

  10. TIMMA-R: an R package for predicting synergistic multi-targeted drug combinations in cancer cell lines or patient-derived samples

    PubMed Central

    He, Liye; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Summary: Network pharmacology-based prediction of multi-targeted drug combinations is becoming a promising strategy to improve anticancer efficacy and safety. We developed a logic-based network algorithm, called Target Inhibition Interaction using Maximization and Minimization Averaging (TIMMA), which predicts the effects of drug combinations based on their binary drug-target interactions and single-drug sensitivity profiles in a given cancer sample. Here, we report the R implementation of the algorithm (TIMMA-R), which is much faster than the original MATLAB code. The major extensions include modeling of multiclass drug-target profiles and network visualization. We also show that the TIMMA-R predictions are robust to the intrinsic noise in the experimental data, thus making it a promising high-throughput tool to prioritize drug combinations in various cancer types for follow-up experimentation or clinical applications. Availability and implementation: TIMMA-R source code is freely available at http://cran.r-project.org/web/packages/timma/. Contact: jing.tang@helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25638808

  11. Multi-targeting exploration of new 2-aminothiazolyl quinolones: Synthesis, antimicrobial evaluation, interaction with DNA, combination with topoisomerase IV and penetrability into cells.

    PubMed

    Cheng, Yu; Avula, Srinivasa Rao; Gao, Wei-Wei; Addla, Dinesh; Tangadanchu, Vijai Kumar Reddy; Zhang, Ling; Lin, Jian-Mei; Zhou, Cheng-He

    2016-11-29

    A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV-DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities.

  12. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: Synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors, and JAK inhibitors

    PubMed Central

    Weisberg, Ellen; Liu, Qingsong; Nelson, Erik; Kung, Andrew L.; Christie, Amanda L.; Bronson, Rod; Sattler, Martin; Sanda, Takaomi; Zhao, Zheng; Hur, Wooyoung; Mitsiades, Constantine; Smith, Robert; Daley, John F.; Stone, Richard; Galinsky, Ilene; Griffin, James D.; Gray, Nathanael

    2014-01-01

    Acute myeloid leukemia (AML) progenitors are frequently characterized by activating mutations in the receptor tyrosine kinase FLT3. Protein tyrosine kinases are integral components of signaling cascades that play a role in both FLT3-mediated transformation as well as viability pathways that are advantageous to leukemic cell survival. The bone marrow microenvironment can diminish AML sensitivity to tyrosine kinase inhibitors (TKIs). We hypothesized that inhibition of protein kinases in addition to FLT3 may be effective in overriding drug resistance in AML. We used a cell-based model mimicking stromal protection as part of an unbiased high-throughput chemical screen to identify kinase inhibitors with the potential to override microenvironment-mediated drug resistance in mutant FLT3-positive AML. Several related multi-targeted kinase inhibitors, including dasatinib, with the capability of reversing microenvironment-induced resistance to FLT3 inhibition were identified and validated. We validated synergy in vitro and demonstrated effective combination potential in vivo. In particular Janus kinase (JAK) inhibitors were effective in overriding stromal protection and potentiating FLT3 inhibition in primary AML and cell lines. These results hint at a novel concept of using combination therapy to override drug resistance in mutant FLT3-positive AML in the bone marrow niche and suppress or eradicate residual disease. PMID:22469781

  13. 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

  14. 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

    2013-09-12

    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.

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

    PubMed

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

    2014-04-01

    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 Aβ 42 self-aggregation, Aβ 42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ 42 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.

  16. 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

  17. Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

    PubMed

    Mathew, Geetha; Unnikrishnan, M K

    2015-10-01

    Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

  18. 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

  19. Multi-Targeted Program Generators

    DTIC Science & Technology

    2004-07-01

    While there is a long history and mature technology for the former, we have just begun to recreate these capabilities at the software architecture...generic technology for dynamically instrumenting software architectures and monitoring their behavior, and several tools for utilizing this capability. It... software architectures. 3. Instrumented Connectors 3.1. Scope This project is developing the technology to monitor the architectural behavior of

  20. 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

  1. Improvement of corrosion protection property of Mg-alloy by DLC and Si-DLC coatings with PBII technique and multi-target DC-RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Masami, Ikeyama; Setsuo, Nakao; Tsutomu, Sonoda; Junho, Choi

    2009-05-01

    Magnesium alloys have been considered as one of the most promising light weight materials with potential applications for automobile and aircraft components. Their poor corrosion resistance, however, has to date prevented wider usage. Diamond-like carbon (DLC) and silicon-incorporated DLC (Si-DLC) coatings are known to provide a high degree of corrosion protection, and hold accordingly promise for enhancing the corrosion resistance of the magnesium alloys. In this work we have studied the effect of coating conditions of DLC coatings as well as Si incorporation into coating on corrosion resistance, deposited onto AZ91 magnesium alloy substrates by plasma based ion implantation (PBII). The influences of a Ti interlayer beneath the DLC, Si-DLC and Ti incorporated DLC (Ti-DLC) coatings fabricated by multi-target direct-current radio-frequency (DC-RF) magnetron sputtering were also examined on both the adhesion strength and corrosion resistance of the materials. We have also examined the effect of the Si content in the Si-DLC coatings made by magnetron sputtering on the alloys' corrosion resistance. The results of potentiodynamic polarization measurements demonstrate that Si-DLC coating deposited by PBII exhibits the highest corrosion resistance in an aqueous 0.05 M NaCl solution. Although Ti layer is helpful in increasing adhesion between DLC coating and AZ91 substrate, it also influences adversely corrosion protection. The ozone treatment of the magnesium alloy's surface before the formation of coatings has been found to improve both adhesion strength and corrosion resistance.

  2. New insights into pharmacological profile of LASSBio-579, a multi-target N-phenylpiperazine derivative active on animal models of schizophrenia.

    PubMed

    Neves, Gilda; Antonio, Camila B; Betti, Andresa H; Pranke, Mariana A; Fraga, Carlos A M; Barreiro, Eliezer J; Noël, François; Rates, Stela M K

    2013-01-15

    Previous behavioral and receptor binding studies on N-phenylpiperazine derivatives by our group indicated that LASSBio-579, LASSBio-580 and LASSBio-581 could be potential antipsychotic lead compounds. The present study identified LASSBio-579 as the most promising among the three compounds, since it was the only one that inhibited apomorphine-induced climbing (5 mg/kg p.o.) and apomorphine-induced hypothermia (15 mg/kg p.o.). Furthermore, LASSBio-579 (0.5 mg/kg p.o.) was effective in the ketamine-induced hyperlocomotion test and prevented the prepulse inhibition deficits induced by apomorphine, DOI and ketamine with different potencies (1 mg/kg, 0.5 mg/kg and 5 mg/kg p.o., respectively). LASSBio-579 also induced a motor impairment, catalepsy and a mild sedative effect but only at doses 3-120 times higher than those with antipsychotic-like effects. In addition, LASSBio-579 (0.5 and 1 mg/kg p.o.) reversed the catalepsy induced by WAY 100,635, corroborating its action on both dopaminergic and serotonergic neurotransmission and pointing to the contribution of 5-HT(1A) receptor activation to its pharmacological profile. Moreover, co-administration of sub-effective doses of LASSBio-579 with sub-effective doses of clozapine or haloperidol prevented the apomorphine-induced climbing without induction of catalepsy. In summary, our results characterize LASSBio-579 as a multi-target ligand active in pharmacological animal models of schizophrenia, confirming that this compound could be included in development programs aiming at a new drug for treating schizophrenia.

  3. [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

  4. 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

  5. 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. © 2011 John Wiley & Sons A/S.

  6. In silico search for multi-target therapies for osteoarthritis based on 10 common Huoxue Huayu herbs and potential applications to other diseases.

    PubMed

    Zheng, Chun-Song; Zhuang, Zhi-Qiang; Xu, Xiao-Jie; Ye, Jin-Xia; Ye, Hong-Zhi; Li, Xi-Hai; Wu, Guang-Wen; Xu, Hui-Feng; Liu, Xian-Xiang

    2014-03-01

    Huoxue Huayu (HXHY) has been widely used in traditional Chinese medicine (TCM) as a key therapeutic principle for osteoarthritis (OA), and related herbs have been widely prescribed to treat OA in the clinic. The aims of the present study were to explore a multi-target therapy for OA using 10 common HXHY herbs and to investigate their potential applications for treatment of other diseases. A novel computational simulation approach that integrates chemical structure, ligand clusters, chemical space and drug‑likeness evaluations, as well as docking and network analysis, was used to investigate the properties and effects of the herbs. The compounds contained in the studied HXHY herbs were divided into 10 clusters. Comparison of the chemical properties of these compounds to those of other compounds described in the DrugBank database indicated that the properties of the former are more diverse than those of the latter and that most of the HXHY-derived compounds do not violate the 'Lipinski's rule of five'. Docking analysis allowed for the identification of 39 potential bioactive compounds from HXHY herbs and 11 potential targets for these compounds. The identified targets were closely associated with 49 diseases, including neoplasms, musculoskeletal, nervous system and cardiovascular diseases. Ligand‑target (L‑T) and ligand‑target‑disease (L‑T‑D) networks were constructed in order to further elucidate the pharmacological effects of the herbs. Our findings suggest that a number of compounds from HXHY herbs are promising candidates for mult‑target therapeutic application in OA and may exert diverse pharmacological effects, affecting additional diseases besides OA.

  7. High-throughput screening for various classes of doping agents using a new 'dilute-and-shoot' liquid chromatography-tandem mass spectrometry multi-target approach.

    PubMed

    Guddat, S; Solymos, E; Orlovius, A; Thomas, A; Sigmund, G; Geyer, H; Thevis, M; Schänzer, W

    2011-01-01

    A new multi-target approach based on liquid chromatography--electrospray ionization tandem mass spectrometry (LC-(ESI)-MS/MS) is presented to screen for various classes of prohibited substances using direct injection of urine specimens. With a highly sensitive new generation hybrid mass spectrometer classic groups of drugs--for example, diuretics, beta2-agonists--stimulants and narcotics are detectable at concentration levels far below the required limits. Additionally, more challenging and various new target compounds could be implemented. Model compounds of stimulant conjugates were studied to investigate a possible screening without complex sample preparation. As a main achievement, the integration of the plasma volume expanders dextran and hydroxyethyl starch (HES), commonly analyzed in time-consuming, stand-alone procedures, is accomplished. To screen for relatively new prohibited compounds, a common metabolite of the selective androgen receptor modulator (SARMs) andarine, a metabolite of growth hormone releasing peptide (GHRP-2), and 5-amino-4-imidazolecarboxyamide ribonucleoside (AICAR) are analyzed. Following a completely new approach, conjugates of di(2-ethylhexyl) phthalate (DEHP) metabolites are monitored to detect abnormally high levels of plasticizers indicating for illicit blood transfusion. The assay was fully validated for qualitative purposes considering the parameters specificity, intra- (3.2-16.6%) and inter-day precision (0.4-19.9%) at low, medium and high concentration, robustness, limit of detection (1-70 ng/ml, dextran: 30 µg/ml, HES: 10 µg/ml) and ion suppression/enhancement effects. The analyses of post-administration and routine doping control samples demonstrates the applicability of the method for sports drug testing. This straightforward and reliable approach accomplishes the combination of different screening procedures resulting in a high-throughput method that increases the efficiency of the labs daily work.

  8. Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

    PubMed

    Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

    2016-11-29

    As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT6 receptor (Kb = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC50hAChE = 12 nM, IC50hBuChE = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD.

  9. Pro-neurogenic, Memory-Enhancing and Anti-stress Effects of DF302, a Novel Fluorine Gamma-Carboline Derivative with Multi-target Mechanism of Action.

    PubMed

    Strekalova, Tatyana; Bahzenova, Nataliia; Trofimov, Alexander; Schmitt-Böhrer, Angelika G; Markova, Nataliia; Grigoriev, Vladimir; Zamoyski, Vladimir; Serkova, Tatiana; Redkozubova, Olga; Vinogradova, Daria; Umriukhin, Alexei; Fisenko, Vladimir; Lillesaar, Christina; Shevtsova, Elena; Sokolov, Vladimir; Aksinenko, Alexey; Lesch, Klaus-Peter; Bachurin, Sergey

    2017-08-30

    A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

  10. SU-E-T-453: Image-Guided Patient-Specific Quality Assurance for Multi-Target Single Isocenter Intracranial VMAT Radiosurgery

    SciTech Connect

    Huang, M; Brezovich, I; Duan, J; Wu, X; Shen, S; Cardan, R.; Fiveash, J; Popple, R

    2015-06-15

    Purpose: To demonstrate a patient specific, image-guided quality assurance method that tests both dosimetric and geometric accuracy for single-isocenter multiple-target VMAT radiosurgery (SIMT-VMAT-SRS) Method: We used a new film type, EBT-XD (optimal range 0.4–40Gy), and an in-house PMMA phantom having a coronal plane for film and a 0.125 cm3 ionization chamber (IC). The phantom contained fiducial features for kV image guided setup and for accurate film marking. Five patient plans with multiple targets sizes ranging from 3 to 21mm in diameter and prescribed doses from 14 to 18 Gy were selected. Two verification plans were generated for each case with the film plane passing through the center of the largest and smallest targets. For the four largest targets we obtained an IC measurement. For each case, a calibration film was irradiated using a custom designed step pattern. The films were scanned using a flatbed color scanner and converted to dose using the calibration film and the three channel calibration method. Image registration was performed between film and treatment planning system calculations to evaluate the geometric accuracy. Results: The mean registration vector had an average magnitude of 0.47 mm (range from 0.13mm to 0.64 mm). For the four largest targets, the mean ratio of the IC and film measurement to expected dose was 0.990 (range 0.968 to 1.009) and 1.032 (1.021 to 1.046), respectively. The fraction of pixels having gamma index < 1 for criteria of 3%/3mm, 3%/2mm, 3%/1mm was 98.8%, 97.5% and 87.2% before geometric registration and 99.1%, 98.3% and 94.8% after registration. Conclusion: We have demonstrated an image-guided QA method can assess both geometric and dosimetric accuracy. The phantom was positioned with sub-millimeter accuracy. Absolute film dosimetry using EBT-XD film was sufficiently accurate for assessment of dose to multi-targets too small for IC measurement in SRS VMAT plans.

  11. HM015k, a Novel Silybin Derivative, Multi-Targets Metastatic Ovarian Cancer Cells and Is Safe in Zebrafish Toxicity Studies

    PubMed Central

    Amawi, Haneen; Hussein, Noor A.; Karthikeyan, Chandrabose; Manivannan, Elangovan; Wisner, Alexander; Williams, Frederick E.; Samuel, Temesgen; Trivedi, Piyush; Ashby, Charles R.; Tiwari, Amit K.

    2017-01-01

    This study was designed to determine the in vitro mechanisms by which the novel silybin derivative, (E)-3-(3-(benzyloxy) phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (HM015k or 15k), produces its anticancer efficacy in ovarian cancer cells. Compound 15k induced apoptosis in ovarian cancer cells in a time-dependent manner by significantly upregulating the expression of Bax and Bak and downregulating the expression of Bcl-2. Interestingly, 15k induced the cleavage of Bax p21 into its more efficacious cleaved form, Bax p18. In addition, caspase 3 and caspase 9 were cleaved to their active forms, inducing the cleavage of poly ADP ribose polymerase (PARP) and β-catenin. Furthermore, in OV2008 cells, 15k induced significant cleavage in nuclear β-catenin to primarily inactive fragments of lower molecular weight. Furthermore, 15k reversed the metastatic potential of OV2008 cells by inhibiting their migration and invasiveness. The mesenchymal phenotype in OV2008 was reversed by 15k, causing cells to be rounder with epithelial—like phenotypes. The 15k-induced reversal was further confirmed by significant upregulation of the E-cadherin expression, an epithelial marker, while N-cadherin, a mesenchymal marker, was downregulated in OV2008 cells. Compound 15k inhibited the expression of the oncogenic c-Myc protein, downregulated proteins DVL3 and DVL2 and significantly upregulated cyclin B1. Also, 15k significantly downregulated the expression levels of ABCG2 and ABCB1 transporters in resistant ABCG2 overexpressing H460/MX20 and resistant ABCB1 overexpressing MDCK/MDR1 cells, respectively. Finally, 15k was safe in zebrafish in vivo model at concentrations up to 10 μM and induced no major toxicities in cardiac, morphology and swimming position parameters. Overall, 15k is a multi-targeted inhibitor with efficacy against metastatic and resistant ovarian cancer. Future in vivo studies will be conducted to determine the efficacy of 15k in tumor-bearing animals. PMID:28824426

  12. Organic-inorganic nano-composite films for photonic applications made by multi-beam multi-target pulsed laser deposition with remote control of the plume directions

    NASA Astrophysics Data System (ADS)

    Darwish, Abdalla M.; Moore, Shaelynn; Mohammed, Aziz; Alexander, Deonte'; Bastian, Tyler; Dorlus, Wydglif; Sarkisov, Sergey S.; Patel, Darayas N.; Mele, Paolo; Koplitz, Brent

    2016-09-01

    the components of different nature, organic polymers and inorganic dopants, in the same target at a certain proportion and exposing them to the same laser beam not necessarily brings good quality nano-composite films. The laser pulse energy and wavelength cannot be optimized for each component individually. Also, the mixing proportion in the composite film is dictated by the initial proportion of the target and thus cannot be changed in the process. These limitations were removed in the recently proposed method of multi-beam and multi-target deposition (in its doublebeam/ dual-target variation) using a MAPLE polymer target and one inorganic target, each being concurrently exposed to laser beams of different wavelengths.5-14 Using the method, nano-composite films of polymer poly(methyl methacrylate) known as PMMA doped with a rare earth (RE) inorganic upconversion phosphor compounds were prepared. Also, a nano-composite film of thermoelectric film of inorganic aluminum-doped ZnO known as AZO was impregnated with PMMA nano-fillers with the purpose of improving electrical conductivity and thermoelectric performance.10, 14 The polymer target was a frozen (to a temperature of liquid nitrogen) PMMA solution in chlorobenzene exposed to a 1064- nm laser beam from a Q-switched Nd:YAG pulsed laser. The inorganic targets were the pellets made of the compressed micro-powders of highly efficient RE-doped NaYF4 or the sintered powder of AZO concurrently ablated with the

  13. Particle separation

    DOEpatents

    Moosmuller, Hans [Reno, NV; Chakrabarty, Rajan K [Reno, NV; Arnott, W Patrick [Reno, NV

    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.

  14. 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.

  15. 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.

  16. A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties.

    PubMed

    Islam, Nazar Ul; Amin, Raza; Shahid, Muhammad; Amin, Muhammad; Zaib, Sumera; Iqbal, Jamshed

    2017-05-23

    Phytotherapeutics exhibit diverse pharmacological effects that are based on the combined action of a mixture of phytoconstituents. In this study, Prunus domestica gum-loaded, stabilized gold and silver nanoparticles (Au/Ag-NPs) were evaluated for their prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory, and analgesic properties. Au/Ag-NPs were biosynthesized and characterized with UV-Vis, FTIR, SEM, EDX, and XRD techniques. The effect of gum and metal ion concentration, reaction temperature, and time on the synthetic stability of nanoparticles was studied along with their post-synthetic stability against varying pH and salt concentrations, long-term storage and extremes of temperature. Nanoparticles were tested for anticancer (HeLa cervical cancer cells), antibacterial (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), urease inhibition (jack-bean urease), anti-inflammatory (carrageenan-induced paw edema), and antinociceptive (abdominal constriction response) activities. The nanoparticles were mostly spherical with an average particle size between 7 and 30 nm (Au-NPs) and 5-30 nm (Ag-NPs). Au/Ag-NPs maintained their colloidal stability and nanoscale characteristics against variations in physicochemical factors. Au/Ag-NPs have potent anticancer potential (IC50 = 2.14 ± 0.15 μg/mL and 3.45 ± 0.23 μg/mL). Au/Ag-NPs selectively suppressed the growth of S. aureus (10.5 ± 0.6 mm, 19.7 ± 0.4 mm), E. coli (10 ± 0.4 mm, 14.4 ± 0.7 mm), and P. aeruginosa (8.2 ± 0.3 mm, 13.1 ± 0.2 mm), as well as showed preferential inhibition against jack-bean urease (19.2 ± 0.86%, 21.5 ± 1.17%). At doses of 40 and 80 mg/kg, Au-NPs significantly ameliorated the increase in paw edema during the 1st h (P < 0.05, P < 0.01) and 2-5 h (P < 0.001) of carrageenan-induced inflammation compared to the 200 and 400 mg/kg doses of P. domestica gum (P < 0.05, P < 0.001). At similar doses, Au-NPs also

  17. 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.

  18. Particle separator

    DOEpatents

    Hendricks, Charles D.

    1990-01-01

    Method and apparatus (10) are provided for separating and classifying particles (48,50,56) by dispersing the particles within a fluid (52) that is upwardly flowing within a cone-shaped pipe (12) that has its large end (20) above its small end (18). Particles of similar size and shape (48,50) migrate to individual levels (A,B) within the flowing fluid. As the fluid is deflected by a plate (42) at the top end of the pipe (12), the smallest particles are collected on a shelf-like flange (40). Ever larger particles are collected as the flow rate of the fluid is increased. To prevent particle sticking on the walls (14) of the pipe (12), additional fluid is caused to flow into the pipe (12) through holes (68) that are specifically provided for that purpose. Sticking is further prevented by high frequency vibrators (70) that are positioned on the apparatus (10).

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Particle preconcentrator

    DOEpatents

    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.

  5. Particle preconcentrator

    DOEpatents

    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.

  6. 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.

  7. 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.

  8. 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.

  9. Auroral particles

    NASA Astrophysics Data System (ADS)

    Evans, David S.

    1987-06-01

    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.

  10. 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.

  11. A Multi-Target Survey. Volume I.

    DTIC Science & Technology

    1979-12-01

    track assignment. In this report, the need for state estimation to identify feasible tracks is ’. eliminated. The use of simpler input-output models ...generally, been based on state-space models and recursive filtering methods. The new aspects of the multitarget tracking problem stem from the necessity for...mathematical model for the problem. Suppose that Mk, fk-1, 2, ---1 measurement vectors zi(tk), =i 1, 2, .-. , k j are obtained at meass- *urement time tk. These

  12. 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.

  13. A Multi-Target Survey. Volume II.

    DTIC Science & Technology

    1979-12-01

    clutter and/or measure- feasible frack does not correspond to a best surveillance picture. This men ts from another targt. In order for correct...allocation of data to a is quite easy to do if the tracks overlap and compete for the ame given track to be made. one must have an effective scoring formula...data is. To be effective , a soing formula must produce (on the ave surements to a track. However. once a decision has bo made that a age) a better

  14. Multi-targeted interference-free determination of ten β-blockers in human urine and plasma samples by alternating trilinear decomposition algorithm-assisted liquid chromatography-mass spectrometry in full scan mode: comparison with multiple reaction monitoring.

    PubMed

    Gu, Hui-Wen; Wu, Hai-Long; Yin, Xiao-Li; Li, Yong; Liu, Ya-Juan; Xia, Hui; Zhang, Shu-Rong; Jin, Yi-Feng; Sun, Xiao-Dong; Yu, Ru-Qin; Yang, Peng-Yuan; Lu, Hao-Jie

    2014-10-27

    β-blockers are the first-line therapeutic agents for treating cardiovascular diseases and also a class of prohibited substances in athletic competitions. In this work, a smart strategy that combines three-way liquid chromatography-mass spectrometry (LC-MS) data with second-order calibration method based on alternating trilinear decomposition (ATLD) algorithm was developed for simultaneous determination of ten β-blockers in human urine and plasma samples. This flexible strategy proved to be a useful tool to solve the problems of overlapped peaks and uncalibrated interferences encountered in quantitative LC-MS, and made the multi-targeted interference-free qualitative and quantitative analysis of β-blockers in complex matrices possible. The limits of detection were in the range of 2.0×10(-5)-6.2×10(-3) μg mL(-1), and the average recoveries were between 90 and 110% with standard deviations and average relative prediction errors less than 10%, indicating that the strategy could provide satisfactory prediction results for ten β-blockers in human urine and plasma samples only using liquid chromatography hyphenated single-quadrupole mass spectrometer in full scan mode. To further confirm the feasibility and reliability of the proposed method, the same batch samples were analyzed by multiple reaction monitoring (MRM) method. T-test demonstrated that there are no significant differences between the prediction results of the two methods. Considering the advantages of fast, low-cost, high sensitivity, and no need of complicated chromatographic and tandem mass spectrometric conditions optimization, the proposed strategy is expected to be extended as an attractive alternative method to quantify analyte(s) of interest in complex systems such as cells, biological fluids, food, environment, pharmaceuticals and other complex samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. "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.

  16. Mechanical properties, chemical analysis and evaluation of antimicrobial response of Si-DLC coatings fabricated on AISI 316 LVM substrate by a multi-target DC-RF magnetron sputtering method for potential biomedical applications

    NASA Astrophysics Data System (ADS)

    Bociaga, Dorota; Sobczyk-Guzenda, Anna; Szymanski, Witold; Jedrzejczak, Anna; Jastrzebska, Aleksandra; Olejnik, Anna; Jastrzebski, Krzysztof

    2017-09-01

    In this study silicon doped diamond-like carbon (Si-DLC) coatings were synthesized on two substrates: silicon and AISI 316LVM stainless steel using a multi-target DC-RF magnetron sputtering method. The Si content in the films ranged between 4 and 16 at.%, and was controlled by the electrical power applied in RF regime to Si cathode target. The character of the chemical bonds was revealed by FTIR analysis. With the addition of silicon the hydroxyl absorption (band in the range of 3200-3600 cm-1) increased what suggests more hydrophilic character of the coating. There were also observed significant changes in bonding of Si atoms. For low content of dopant, Si-O-Si bond system is predominant, while for the highest content of silicon there is an evidence of the shift to Si-C bonds in close proximity to methyl groups. The Raman spectroscopy revealed that the G peak position is shifted to a lower wavenumber and the ID/IG ratio decreased with increasing Si content, which indicates an increase in the C-sp3 content. Regardless of the coatings' composition, the improvement of hardness in comparison to pure substrate material (AISI 316 LVM) was observed. Although the reduction of the level of hardness from the level of 10.8 GPa for pure DLC to about 9.4 GPa for the silicon doped coatings was observed, the concomitant improvement of films adhesion with higher amount of Si was revealed. Although incorporation of the dopant to DLC coatings increases the number of E. coli cells which adhered to the examined surfaces, the microbial colonisation remains on the level of substrate material. The presented results prove the potential of Si-DLC coatings in biomedical applications from the point of view of their mechanical properties.

  17. Interacting with Multi-Robot Systems Using BML

    DTIC Science & Technology

    2013-06-01

    as to how those tasks assignments can be defined, formulated and exchanged. Our approach : formulate orders (as well as the reports the robots send...within the MRS easily. © Fraunhofer FKIE Communication Architecture ~ ~ Fraunhofer FKIE © Fraunhofer FKIE Battle Mangement Language BML...Fraunhofer FKIE Battle Mangement Language Orders Orders move patrol observe distribute guard recce imagery intelligence gathering

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Multi-Robot FastSLAM for Large Domains

    DTIC Science & Technology

    2007-03-01

    LARGE DOMAINS THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School of Engineering and Management...Air Force Institute of Technology Air University Air Education and Training Command In Partial Fulfillment of the Requirements for the Degree of...in our offices and homes . Like humans, robots rely on sensor measurements to interpret theirs environment and subsequently build maps using the

  3. Learning to Role-Switch in Multi-Robot Systems

    DTIC Science & Technology

    2006-01-01

    Reinforcement Learning [16,17], as used today for coordination in behavior-based robotics, has appeared in a variety of tasks aimed at taking known...competencies and building more complex behavior or improved performance. Asada et al [2] demonstrated how reinforcement learning could learn... reinforcement learning mechanism. Diettrich [5], in his work on Hierarchical Reinforcement Learning with MAXQ, alludes to the possibility, as does

  4. A Gradient Optimization Approach to Adaptive Multi-Robot Control

    DTIC Science & Technology

    2009-09-01

    Remark 4.4 Another commonly used weighting for algorithms over communication graphs is 1 for j E c wij - 0 for j , Ari , where ANi is the set of...1 v2 . VN-1 ]T, and 4 i [ 01 T ... N-2T clT ... N-2T ].15) .. "i ..... i "r OVi and uT and v[ are obtained from (7.10). The Least Squares problem is...trial, three free-ranging mature beef cattle of Hereford and Hereford x Brangus genetics , labeled Cow 1-Cow 3, were fitted with the sensor boxes

  5. UPenn Multi-Robot Unmanned Vehicle System (MAGIC)

    DTIC Science & Technology

    2014-05-05

    electronics, computation , and highly capable propulsion and actuation. The mapping, navigation, and planning software is organized hierarchically... computation , and highly capable propulsion and actuation. The mapping, navigation, and planning software is organized hierarchically, allowing...and complementary sensors, integrated electronics, computation , and highly capable propulsion and actuation. The mapping, navigation, and planning

  6. 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.

  7. Stable particles

    SciTech Connect

    Samios, N.P.

    1993-12-31

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc.

  8. 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

  9. Particle Geophysics

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiroyuki K. M.

    2014-05-01

    Geophysics research has long been dominated by classical mechanics, largely disregarding the potential of particle physics to augment existing techniques. The purpose of this article is to review recent progress in probing Earth's interior with muons and neutrinos. Existing results for various volcanological targets are reviewed. Geoneutrinos are also highlighted as examples in which the neutrino probes elucidate the composition of Earth's deep interior. Particle geophysics has the potential to serve as a useful paradigm to transform our understanding of Earth as dramatically as the X-ray transformed our understanding of medicine and the body.

  10. 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.

  11. Airborne Particles.

    ERIC Educational Resources Information Center

    Ojala, Carl F.; Ojala, Eric J.

    1987-01-01

    Describes an activity in which students collect airborne particles using a common vacuum cleaner. Suggests ways for the students to convert their data into information related to air pollution and human health. Urges consideration of weather patterns when analyzing the results of the investigation. (TW)

  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 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.

  14. Particle classifier

    SciTech Connect

    Etkin, B.

    1987-04-14

    This patent describes a classifier for particulate material comprising a housing having an inlet to receive a classifying air flow flowing in a given direction, collection means downstream of the inlet to receive material classified by the air flow, and material introduction means intermediate the inlet and the collection means to introduce particles entrained in a secondary air stream into the housing in a direction other than the given direction. The material introduction means includes a material outlet aperture in a wall of the housing extending generally perpendicular to the given direction, conveying means to convey material and the secondary air stream to the material outlet and diverting means to divert the secondary air stream to a direction generally parallel to the classifying air flow flowing in the given direction. The diverting means includes a surface extending downstream from the outlet and adjacent thereto and being dimensioned to divert the secondary airstream by a Coanda effect generally parallel to the given direction and thereby segregate the secondary air/stream from the particles and permit continued movement of the particles along predictable trajectories.

  15. Martian Particle

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image of Martian soil was taken by the Phoenix Lander's atomic force microscope on Sol 74 of the mission, which began on May 25, 2008. This image of a flat, smooth-surfaced particle is consistent with the appearance of soil from Earth containing the mineral phyllosilicate.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by JPL, Pasadena, Calif. Spacecraft development was by Lockheed Martin Space Systems, Denver.

  16. Molecular quantum robotics: particle and wave solutions, illustrated by "leg-over-leg" walking along microtubules.

    PubMed

    Levi, Paul

    2015-01-01

    Remarkable biological examples of molecular robots are the proteins kinesin-1 and dynein, which move and transport cargo down microtubule "highways," e.g., of the axon, to final nerve nodes or along dendrites. They convert the energy of ATP hydrolysis into mechanical forces and can thereby push them forwards or backwards step by step. Such mechano-chemical cycles that generate conformal changes are essential for transport on all different types of substrate lanes. The step length of an individual molecular robot is a matter of nanometers but the dynamics of each individual step cannot be predicted with certainty (as it is a random process). Hence, our proposal is to involve the methods of quantum field theory (QFT) to describe an overall reliable, multi-robot system that is composed of a huge set of unreliable, local elements. The methods of QFT deliver techniques that are also computationally demanding to synchronize the motion of these molecular robots on one substrate lane as well as across lanes. Three different challenging types of solutions are elaborated. The impact solution reflects the particle point of view; the two remaining solutions are wave based. The second solution outlines coherent robot motions on different lanes. The third solution describes running waves. Experimental investigations are needed to clarify under which biological conditions such different solutions occur. Moreover, such a nano-chemical system can be stimulated by external signals, and this opens a new, hybrid approach to analyze and control the combined system of robots and microtubules externally. Such a method offers the chance to detect mal-functions of the biological system.

  17. 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.

  18. Dynamics of Carroll particles

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric; Gomis, Joaquim; Longhi, Giorgio

    2014-10-01

    We investigate particles whose dynamics are invariant under the Carroll group. Although a single, free such Carroll particle has no non-trivial dynamics (the Carroll particle does not move), we show that non-trivial dynamics exists for a set of interacting Carroll particles. Furthermore, we gauge the Carroll algebra and couple the Carroll particle to these gauge fields. It turns out that for such a coupled system, even a single Carroll particle can have non-trivial dynamics.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Particle Tracks in Aerogel

    NASA Image and Video Library

    2005-11-03

    In an experiment using a special air gun, particles are shot into aerogel at high velocities. Closeup of particles leaving a carrot-shaped trail in the aerogel are shown here. Aerogel was used on NASA Stardust spacecraft.

  4. Charged Particle Flux Sensor

    NASA Technical Reports Server (NTRS)

    Gregory, D. A.; Stocks, C. D.

    1983-01-01

    Improved version of Faraday cup increases accuracy of measurements of flux density of charged particles incident along axis through collection aperture. Geometry of cone-and-sensing cup combination assures most particles are trapped.

  5. 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.

  6. 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...

  7. Solar Neutral Particles

    NASA Image and Video Library

    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 ...

  8. Particle physics: Axions exposed

    NASA Astrophysics Data System (ADS)

    Lombardo, Maria Paola

    2016-11-01

    Physicists are hunting for a particle called the axion that could solve two major puzzles in fundamental physics. An ambitious study calculates the expected mass of this particle, which might reshape the experimental searches. See Letter p.69

  9. 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...

  10. Axionlike particle assisted strongly interacting massive particle

    NASA Astrophysics Data System (ADS)

    Kamada, Ayuki; Kim, Hyungjin; Sekiguchi, Toyokazu

    2017-07-01

    We propose a new realization of strongly interacting massive particles (SIMPs) as self-interacting dark matter, where SIMPs couple to the standard model (SM) sector through an axionlike particle. Our model overcomes major obstacles accompanying the original SIMP model, such as a missing mechanism of kinetically equilibrating SIMPs with the SM plasma as well as marginal perturbativity of the chiral Lagrangian density. Remarkably, the parameter region realizing σself/mDM≃0.1 - 1 cm2/g is within the reach of future beam dump experiments such as the Search for Hidden Particles experiment.

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. Particle charge spectrometer

    NASA Technical Reports Server (NTRS)

    Fuerstenau, Stephen D. (Inventor)

    2004-01-01

    An airflow through a tube is used to guide a charged particle through the tube. A detector may be used to detect charge passing through the tube on the particle. The movement of the particle through the tube may be used to both detect its charge and size.

  16. 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…

  17. 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…

  18. 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.

  19. 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.

  20. Primordial Particles; Collisions of Inelastic Particles

    NASA Astrophysics Data System (ADS)

    Sagi, George

    2011-03-01

    Three-dimensional matter is not defined by Euclidian or Cartesian geometries. Newton's and Einstein's laws are related to the motions of elastic masses. The study of collisions of inelastic particles opens up new vistas in physics. The present article reveals how such particles create clusters composed of various numbers of particles. The Probability of each formation, duplets, triplets, etc. can be calculated. The particles are held together by a binding force, and depending upon the angles of collisions they may also rotate around their center of geometry. Because of these unique properties such inelastic particles are referred to as primordial particles, Pp. When a given density of Pp per cubic space is given, then random collisions create a field. The calculation of the properties of such primordial field is very complex and beyond the present study. However, the angles of collisions are infinite in principle, but the probabilities of various cluster sizes are quantum dependent. Consequently, field calculations will require new complex mathematical methods to be discovered yet.

  1. Particle Accelerators in China

    NASA Astrophysics Data System (ADS)

    Zhang, Chuang; Fang, Shouxian

    As the special machines that can accelerate charged particle beams to high energy by using electromagnetic fields, particle accelerators have been widely applied in scientific research and various areas of society. The development of particle accelerators in China started in the early 1950s. After a brief review of the history of accelerators, this article describes in the following sections: particle colliders, heavy-ion accelerators, high-intensity proton accelerators, accelerator-based light sources, pulsed power accelerators, small scale accelerators, accelerators for applications, accelerator technology development and advanced accelerator concepts. The prospects of particle accelerators in China are also presented.

  2. Fluidization of spherocylindrical particles

    NASA Astrophysics Data System (ADS)

    Mahajan, Vinay V.; Nijssen, Tim M. J.; Fitzgerald, Barry W.; Hofman, Jeroen; Kuipers, Hans; Padding, Johan T.

    2017-06-01

    Multiphase (gas-solid) flows are encountered in numerous industrial applications such as pharmaceutical, food, agricultural processing and energy generation. A coupled computational fluid dynamics (CFD) and discrete element method (DEM) approach is a popular way to study such flows at a particle scale. However, most of these studies deal with spherical particles while in reality, the particles are rarely spherical. The particle shape can have significant effect on hydrodynamics in a fluidized bed. Moreover, most studies in literature use inaccurate drag laws because accurate laws are not readily available. The drag force acting on a non-spherical particle can vary considerably with particle shape, orientation with the flow, Reynolds number and packing fraction. In this work, the CFD-DEM approach is extended to model a laboratory scale fluidized bed of spherocylinder (rod-like) particles. These rod-like particles can be classified as Geldart D particles and have an aspect ratio of 4. Experiments are performed to study the particle flow behavior in a quasi-2D fluidized bed. Numerically obtained results for pressure drop and bed height are compared with experiments. The capability of CFD-DEM approach to efficiently describe the global bed dynamics for fluidized bed of rod-like particles is demonstrated.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Detecting Space Dust Particles

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Humes, Donald H.; Kassel, Philip C., Jr.; Wortman, Jim; Singer, S. Fred; Stanley, John

    1988-01-01

    Technique records times specific craters formed in targets exposed in space and permits determination of direction in which impacting particles traveled at times of impacts. MOS capacitor is short-circuited by impact of particle striking at high speed. After recovery of targets from space, compositions of impacting particles established through post-flight laboratory analyses of residual materials in craters. On earth technique has industrial and military uses in detection of fragments driven by explosions. Studies of orbital dynamics of particles produced by solid-propellant rocket-motor firings in space made using technique.

  11. Vaporizing particle velocimeter

    NASA Technical Reports Server (NTRS)

    Weinstein, Leonard M. (Inventor)

    1992-01-01

    A velocimeter measures flow characteristics of a flow traveling through a chamber in a given direction. Tracer particles are entrained in the flow and a source of radiant energy produces an output stream directed transversely to the chamber, having a sufficient intensity to vaporize the particles as they pass through the output stream. Each of the vaporized particles explodes to produce a shock wave and a hot core, and a flow visualization system tracks the motion of the hot cores and shock waves to measure the velocity of each tracer particle and the temperature of the flow around the tracer.

  12. Review of Particle Physics

    NASA Astrophysics Data System (ADS)

    Beringer, J.; Arguin, J.-F.; Barnett, R. M.; Copic, K.; Dahl, O.; Groom, D. E.; Lin, C.-J.; Lys, J.; Murayama, H.; Wohl, C. G.; Yao, W.-M.; Zyla, P. A.; Amsler, C.; Antonelli, M.; Asner, D. M.; Baer, H.; Band, H. R.; Basaglia, T.; Bauer, C. W.; Beatty, J. J.; Belousov, V. I.; Bergren, E.; Bernardi, G.; Bertl, W.; Bethke, S.; Bichsel, H.; Biebel, O.; Blucher, E.; Blusk, S.; Brooijmans, G.; Buchmueller, O.; Cahn, R. N.; Carena, M.; Ceccucci, A.; Chakraborty, D.; Chen, M.-C.; Chivukula, R. S.; Cowan, G.; D'Ambrosio, G.; Damour, T.; de Florian, D.; de Gouvêa, A.; DeGrand, T.; de Jong, P.; Dissertori, G.; Dobrescu, B.; Doser, M.; Drees, M.; Edwards, D. A.; Eidelman, S.; Erler, J.; Ezhela, V. V.; Fetscher, W.; Fields, B. D.; Foster, B.; Gaisser, T. K.; Garren, L.; Gerber, H.-J.; Gerbier, G.; Gherghetta, T.; Golwala, S.; Goodman, M.; Grab, C.; Gritsan, A. V.; Grivaz, J.-F.; Grünewald, M.; Gurtu, A.; Gutsche, T.; Haber, H. E.; Hagiwara, K.; Hagmann, C.; Hanhart, C.; Hashimoto, S.; Hayes, K. G.; Heffner, M.; Heltsley, B.; Hernández-Rey, J. J.; Hikasa, K.; Höcker, A.; Holder, J.; Holtkamp, A.; Huston, J.; Jackson, J. D.; Johnson, K. F.; Junk, T.; Karlen, D.; Kirkby, D.; Klein, S. R.; Klempt, E.; Kowalewski, R. V.; Krauss, F.; Kreps, M.; Krusche, B.; Kuyanov, Yu. V.; Kwon, Y.; Lahav, O.; Laiho, J.; Langacker, P.; Liddle, A.; Ligeti, Z.; Liss, T. M.; Littenberg, L.; Lugovsky, K. S.; Lugovsky, S. B.; Mannel, T.; Manohar, A. V.; Marciano, W. J.; Martin, A. D.; Masoni, A.; Matthews, J.; Milstead, D.; Miquel, R.; Mönig, K.; Moortgat, F.; Nakamura, K.; Narain, M.; Nason, P.; Navas, S.; Neubert, M.; Nevski, P.; Nir, Y.; Olive, K. A.; Pape, L.; Parsons, J.; Patrignani, C.; Peacock, J. A.; Petcov, S. T.; Piepke, A.; Pomarol, A.; Punzi, G.; Quadt, A.; Raby, S.; Raffelt, G.; Ratcliff, B. N.; Richardson, P.; Roesler, S.; Rolli, S.; Romaniouk, A.; Rosenberg, L. J.; Rosner, J. L.; Sachrajda, C. T.; Sakai, Y.; Salam, G. P.; Sarkar, S.; Sauli, F.; Schneider, O.; Scholberg, K.; Scott, D.; Seligman, W. G.; Shaevitz, M. H.; Sharpe, S. R.; Silari, M.; Sjöstrand, T.; Skands, P.; Smith, J. G.; Smoot, G. F.; Spanier, S.; Spieler, H.; Stahl, A.; Stanev, T.; Stone, S. L.; Sumiyoshi, T.; Syphers, M. J.; Takahashi, F.; Tanabashi, M.; Terning, J.; Titov, M.; Tkachenko, N. P.; Törnqvist, N. A.; Tovey, D.; Valencia, G.; van Bibber, K.; Venanzoni, G.; Vincter, M. G.; Vogel, P.; Vogt, A.; Walkowiak, W.; Walter, C. W.; Ward, D. R.; Watari, T.; Weiglein, G.; Weinberg, E. J.; Wiencke, L. R.; Wolfenstein, L.; Womersley, J.; Woody, C. L.; Workman, R. L.; Yamamoto, A.; Zeller, G. P.; Zenin, O. V.; Zhang, J.; Zhu, R.-Y.; Harper, G.; Lugovsky, V. S.; Schaffner, P.

    2012-07-01

    This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, Vcb & Vub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter.A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov/.The 2012 edition of Review of Particle Physics is published for the Particle Data Group as article 010001 in volume 86 of Physical Review D.This edition should be cited as: J. Beringer et al. (Particle Data Group), Phys. Rev. D 86, 010001 (2012).

  13. Ice particle collisions

    NASA Astrophysics Data System (ADS)

    Sampara, Naresh; Turnbull, Barbara; Hill, Richard; Swift, Michael

    2017-04-01

    Granular interactions of ice occur in a range of geophysical, astrophysical and industrial applications. For example, Saturn's Rings are composed of icy particles from micrometers to kilometres in size - inertial and yet too small to interact gravitationally. In clouds, ice crystals are smashed to pieces before they re-aggregate to for snow floccules in a process that is very much open to interpretation. In a granular flow of ice particles, the energy spent in collisions can lead to localized surface changes and wetting, which in turn can promote aggregation. To understand the induced wetting and its effects, we present two novel experimental methods which provide snippets of insight into the collisional behaviour of macroscopic ice particles. Experiment 1: Microgravity experiments provide minute details of the contact between the ice particles during the collision. A diamagnetic levitation technique, as alternative to the parabolic flight or falling tower experiments, was used to understand the collisional behaviour of individual macroscopic icy bodies. A refrigerated cylinder, that can control ambient conditions, was inserted into the bore of an 18 Tesla superconducting magnet and cooled to -10°C. Initial binary collisions were created, where one 4 mm ice particle was levitated in the magnet bore whilst another particle was dropped vertically from the top of the bore. The trajectories of both particles were captured by high speed video to provide the three-dimensional particle velocities and track the collision outcome. Introducing complexity, multiple particles were levitated in the bore and an azimuthal turbulent air flow introduced, allowing the particles to collide with other particles within a coherent fluid structure (mimicking Saturn's rings, or an eddy in a cloud). In these experiments, a sequence of collisions occur, each one different to the previous one due to the changes in surface characteristics created by the collisions themselves. Aggregation

  14. 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.

  15. 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.

  16. 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.

  17. Solar Energetic Particles

    NASA Astrophysics Data System (ADS)

    Király, Péter

    Energetic particles recorded in the Earth environment and in interplanetary space have a multitude of origins, i.e. acceleration and propagation histories. At early days practically all sufficiently energetic particles were considered to have come either from solar flares or from interstellar space. Later on, co-rotating interplanetary shocks, the termination shock of the supersonic solar wind, planetary bow shocks and magnetospheres, and also coronal mass ejections (CME) were recognized as energetic particle sources. It was also recognized that less energetic (suprathermal) particles of solar origin and pick-up ions have also a vital role in giving rise to energetic particles in interplanetary disturbances. The meaning of the term "solar energetic particles" (SEP) is now somewhat vague, but essentially it refers to particles produced in disturbances fairly directly related to solar processes. Variation of intensity fluctuations with energy and with the phase of the solar cycle will be discussed. Particular attention will be given to extremes of time variation, i.e. to very quiet periods and to large events. While quiet-time fluxes are expected to shed light on some basic coronal processes, large events dominate the fluctuation characteristics of cumulated fluence, and the change of that fluctuation with energy and with the phase of the solar cycle may also provide important clues. Mainly ISEE-3 and long-term IMP-8 data will be invoked. Energetic and suprathermal particles that may never escape into interplanetary space may play an important part in heating the corona of the sun.

  18. Interactive Terascale Particle Visualization

    NASA Technical Reports Server (NTRS)

    Ellsworth, David; Green, Bryan; Moran, Patrick

    2004-01-01

    This paper describes the methods used to produce an interactive visualization of a 2 TB computational fluid dynamics (CFD) data set using particle tracing (streaklines). We use the method introduced by Bruckschen et al. [2001] that pre-computes a large number of particles, stores them on disk using a space-filling curve ordering that minimizes seeks, and then retrieves and displays the particles according to the user's command. We describe how the particle computation can be performed using a PC cluster, how the algorithm can be adapted to work with a multi-block curvilinear mesh, and how the out-of-core visualization can be scaled to 296 billion particles while still achieving interactive performance on PG hardware. Compared to the earlier work, our data set size and total number of particles are an order of magnitude larger. We also describe a new compression technique that allows the lossless compression of the particles by 41% and speeds the particle retrieval by about 30%.

  19. Teaching German Modal Particles.

    ERIC Educational Resources Information Center

    Rosler, Dietmar

    1982-01-01

    Believes modern linguistics has done little to explore German modal particles because by focusing on sentences as the basic category for linguistic thinking these words did not seem to matter. Describes model which gives students experience with these particles in meaningful communication. (Author/BK)

  20. Detecting Contaminant Particles Acoustically

    NASA Technical Reports Server (NTRS)

    Wyett, L. M.

    1986-01-01

    Apparatus "listens" for particles in interior of complex turbomachinery. Contact microphones are attached at several points on pump housing. Acoustic transducer also attached to housing to excite entire pump with sound. Frequency of sound is slowly raised until pump resonates. Microphones detect noise of loose particles scraping against pump parts. Such as machining chips in turbopumps or other machinery without disassembly.

  1. Pileup per particle identification

    DOE PAGES

    Bertolini, Daniele; Harris, Philip; Low, Matthew; ...

    2014-10-09

    We propose a new method for pileup mitigation by implementing “pileup per particle identification” (PUPPI). For each particle we first define a local shape α which probes the collinear versus soft diffuse structure in the neighborhood of the particle. The former is indicative of particles originating from the hard scatter and the latter of particles originating from pileup interactions. The distribution of α for charged pileup, assumed as a proxy for all pileup, is used on an event-by-event basis to calculate a weight for each particle. The weights describe the degree to which particles are pileup-like and are used tomore » rescale their four-momenta, superseding the need for jet-based corrections. Furthermore, the algorithm flexibly allows combination with other, possibly experimental, probabilistic information associated with particles such as vertexing and timing performance. We demonstrate the algorithm improves over existing methods by looking at jet pT and jet mass. As a result, we also find an improvement on non-jet quantities like missing transverse energy.« less

  2. Icy Particle Spray

    NASA Image and Video Library

    2010-11-18

    Images obtained by NASA EPOXI mission spacecraft show an active end of the nucleus of comet Hartley 2. Icy particles spew from the surface. Most of these particles are traveling with the nucleus; fluffy nowballs about 3 centimeters to 30 centimeters.

  3. Particle fuel diversion structure

    SciTech Connect

    Eshleman, R. D.

    1985-07-30

    A particle fuel burning furnace has an upper combustion chamber for holding a pile of particle fuel and burning the same from the bottom thereof. The furnace also includes a lower combustion chamber for after-burning combustible gases given off by the burning of solid fuel in the upper chamber and a series of spaced apart vertically-extending passageways arranged in a row and interconnecting the upper and lower chambers for communicating the combustible gases from the upper to the lower chamber. A first improved feature relates to a particle fuel delivery control device which operates an auger for filling the upper chamber with particle fuel to a desired level. A beam of light is transmitted and reflected between a photoelectric cell and reflector respectively of the device. When the particle fuel pile has grown in height during filling to the desired level the light beam is interrupted and filling is terminated. A second improved feature relates to a particle fuel diversion structure positioned in spaced relationship above and overlying the row of passageways. The structure forms a horizontal slot which extends laterally from the passageways which prevents particles of fuel from falling through the passageways and relocates the flame which burns the particle fuel pile from the bottom to a region away from the passageways.

  4. Ambient Tropospheric Particles

    EPA Science Inventory

    Atmospheric particulate matter (PM) is a complex mixture of solid and liquid particles suspended in ambient air (also known as the atmospheric aerosol). Ambient PM arises from a wide-range of sources and/or processes, and consists of particles of different shapes, sizes, and com...

  5. Pileup per particle identification

    SciTech Connect

    Bertolini, Daniele; Harris, Philip; Low, Matthew; Tran, Nhan

    2014-10-09

    We propose a new method for pileup mitigation by implementing “pileup per particle identification” (PUPPI). For each particle we first define a local shape α which probes the collinear versus soft diffuse structure in the neighborhood of the particle. The former is indicative of particles originating from the hard scatter and the latter of particles originating from pileup interactions. The distribution of α for charged pileup, assumed as a proxy for all pileup, is used on an event-by-event basis to calculate a weight for each particle. The weights describe the degree to which particles are pileup-like and are used to rescale their four-momenta, superseding the need for jet-based corrections. Furthermore, the algorithm flexibly allows combination with other, possibly experimental, probabilistic information associated with particles such as vertexing and timing performance. We demonstrate the algorithm improves over existing methods by looking at jet pT and jet mass. As a result, we also find an improvement on non-jet quantities like missing transverse energy.

  6. RESEARCH IN PARTICLE PHYSICS

    SciTech Connect

    Kearns, Edward

    2013-07-12

    This is the final report for the Department of Energy Grant to Principal Investigators in Experimental and Theoretical Particle Physics at Boston University. The research performed was in the Energy Frontier at the LHC, the Intensity Frontier at Super-Kamiokande and T2K, the Cosmic Frontier and detector R&D in dark matter detector development, and in particle theory.

  7. Ambient Tropospheric Particles

    EPA Science Inventory

    Atmospheric particulate matter (PM) is a complex mixture of solid and liquid particles suspended in ambient air (also known as the atmospheric aerosol). Ambient PM arises from a wide-range of sources and/or processes, and consists of particles of different shapes, sizes, and com...

  8. Teaching German Modal Particles.

    ERIC Educational Resources Information Center

    Rosler, Dietmar

    1982-01-01

    Believes modern linguistics has done little to explore German modal particles because by focusing on sentences as the basic category for linguistic thinking these words did not seem to matter. Describes model which gives students experience with these particles in meaningful communication. (Author/BK)

  9. Particle impact location detector

    NASA Technical Reports Server (NTRS)

    Auer, S. O.

    1974-01-01

    Detector includes delay lines connected to each detector surface strip. When several particles strike different strips simultaneously, pulses generated by each strip are time delayed by certain intervals. Delay time for each strip is known. By observing time delay in pulse, it is possible to locate strip that is struck by particle.

  10. Anisotropic Particles in Turbulence

    NASA Astrophysics Data System (ADS)

    Voth, Greg A.; Soldati, Alfredo

    2017-01-01

    Anisotropic particles are common in many industrial and natural turbulent flows. When these particles are small and neutrally buoyant, they follow Lagrangian trajectories while exhibiting rich orientational dynamics from the coupling of their rotation to the velocity gradients of the turbulence field. This system has proven to be a fascinating application of the fundamental properties of velocity gradients in turbulence. When particles are not neutrally buoyant, they experience preferential concentration and very different preferential alignment than neutrally buoyant tracer particles. A vast proportion of the parameter range of anisotropic particles in turbulence is still unexplored, with most existing research focusing on the simple foundational cases of axisymmetric ellipsoids at low concentrations in homogeneous isotropic turbulence and in turbulent channel flow. Numerical simulations and experiments have recently developed a fairly comprehensive picture of alignment and rotation in these cases, and they provide an essential foundation for addressing more complex problems of practical importance. Macroscopic effects of nonspherical particle dynamics include preferential concentration in coherent structures and drag reduction by fiber suspensions. We review the models used to describe nonspherical particle motion, along with numerical and experimental methods for measuring particle dynamics.

  11. HIGH ENERGY PARTICLE ACCELERATOR

    DOEpatents

    Courant, E.D.; Livingston, M.S.; Snyder, H.S.

    1959-04-14

    An improved apparatus is presented for focusing charged particles in an accelerator. In essence, the invention includes means for establishing a magnetic field in discrete sectors along the path of moving charged particles, the magnetic field varying in each sector in accordance with the relation. B = B/ sub 0/ STAln (r-r/sub 0/)/r/sub 0/!, where B/sub 0/ is the value of the magnetic field at the equilibrium orbit of radius r/sub 0/ of the path of the particles, B equals the magnetic field at the radius r of the chamber and n equals the magnetic field gradient index, the polarity of n being abruptly reversed a plurality of times as the particles travel along their arcuate path. With this arrangement, the particles are alternately converged towards the axis of their equillbrium orbit and diverged therefrom in successive sectors with a resultant focusing effect.

  12. Review of particle physics

    DOE PAGES

    Olive, K. A.

    2016-10-01

    The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders,more » Probability and Statistics. As a result, among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation.« less

  13. Review of particle physics

    SciTech Connect

    Olive, K. A.

    2016-10-01

    The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. As a result, among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation.

  14. Imaging alpha particle detector

    DOEpatents

    Anderson, David F.

    1985-01-01

    A method and apparatus for detecting and imaging alpha particles sources is described. A conducting coated high voltage electrode (1) and a tungsten wire grid (2) constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source (3) to be quantitatively or qualitatively analyzed. A thin polyester film window (4) allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  15. Imaging alpha particle detector

    DOEpatents

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  16. Elementary particles and cosmology

    NASA Astrophysics Data System (ADS)

    Dobrolyubov, M. I.; Ignatev, A. Yu.; Shaposhnikov, M. E.

    1988-12-01

    A series of lectures is devoted to actual problems which arise at the junction of elementary particle physics and cosmology. A brief review is given to the standard theory of hot universe and scenario of inflationary universe, modern state of the problem of baryon universe asymmetry and possible new mechanisms of this asymmetry formation. The possibility of construction of cosmological models on the basis of supersymmetric theories is considered: qualitative evaluation of the modern density of relic particles, cosmological restrictions for the mass of the lightest particle, astrophysical restrictions for the coupling constant of weakly interacting particles and matter are given. A perspective direction of search for light particles in light hadron decays is mentioned.

  17. Particle Analysis Pitfalls

    NASA Technical Reports Server (NTRS)

    Hughes, David; Dazzo, Tony

    2007-01-01

    This viewgraph presentation reviews the use of particle analysis to assist in preparing for the 4th Hubble Space Telescope (HST) Servicing mission. During this mission the Space Telescope Imaging Spectrograph (STIS) will be repaired. The particle analysis consisted of Finite element mesh creation, Black-body viewfactors generated using I-DEAS TMG Thermal Analysis, Grey-body viewfactors calculated using Markov method, Particle distribution modeled using an iterative Monte Carlo process, (time-consuming); in house software called MASTRAM, Differential analysis performed in Excel, and Visualization provided by Tecplot and I-DEAS. Several tests were performed and are reviewed: Conformal Coat Particle Study, Card Extraction Study, Cover Fastener Removal Particle Generation Study, and E-Graf Vibration Particulate Study. The lessons learned during this analysis are also reviewed.

  18. Review of particle physics

    SciTech Connect

    Olive, K. A.

    2016-10-01

    The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. As a result, among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation.

  19. DEM Particle Fracture Model

    SciTech Connect

    Zhang, Boning; Herbold, Eric B.; Homel, Michael A.; Regueiro, Richard A.

    2015-12-01

    An adaptive particle fracture model in poly-ellipsoidal Discrete Element Method is developed. The poly-ellipsoidal particle will break into several sub-poly-ellipsoids by Hoek-Brown fracture criterion based on continuum stress and the maximum tensile stress in contacts. Also Weibull theory is introduced to consider the statistics and size effects on particle strength. Finally, high strain-rate split Hopkinson pressure bar experiment of silica sand is simulated using this newly developed model. Comparisons with experiments show that our particle fracture model can capture the mechanical behavior of this experiment very well, both in stress-strain response and particle size redistribution. The effects of density and packings o the samples are also studied in numerical examples.

  20. A Finite Point Process Approach to Multi-Target Localization

    DTIC Science & Technology

    2013-09-01

    82) Thus Q ( T |T(n) ) = N∑ i=1 Qi ( Ti |T (n) ) + Qcl ( T(n) ) (83) where Qi ( Ti |T (n) ) = s∑ ℓ=1 [ mℓ∑ j=1 log pD(Ti)N ( z (ℓ) j |h(Ti, Sℓ), Σw...pD(T (n) i )N ( z (ℓ) j |h(T (n) i , Sℓ), Σw ) ν(ℓ) ( z (ℓ) j |T (n) ) − ∫ T pD(Ti)N (z|h (Ti, Sℓ ) ,Σw) dz ] (84) and Qcl ( T(n) ) = s∑ ℓ=1

  1. Multi-target electrochemical biosensing enabled by integrated CMOS electronics

    NASA Astrophysics Data System (ADS)

    Rothe, J.; Lewandowska, M. K.; Heer, F.; Frey, O.; Hierlemann, A.

    2011-05-01

    An integrated electrochemical measurement system, based on CMOS technology, is presented, which allows the detection of several analytes in parallel (multi-analyte) and enables simultaneous monitoring at different locations (multi-site). The system comprises a 576-electrode CMOS sensor chip, an FPGA module for chip control and data processing, and the measurement laptop. The advantages of the highly versatile system are demonstrated by two applications. First, a label-free, hybridization-based DNA sensor is enabled by the possibility of large-scale integration in CMOS technology. Second, the detection of the neurotransmitter choline is presented by assembling the chip with biosensor microprobe arrays. The low noise level enables a limit of detection of, e.g., 0.3 µM choline. The fully integrated system is self-contained: it features cleaning, functionalization and measurement functions without the need for additional electrical equipment. With the power supplied by the laptop, the system is very suitable for on-site measurements.

  2. Designing Multi-target Compound Libraries with Gaussian Process Models.

    PubMed

    Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

    2016-05-01

    We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  3. 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

  4. Multi-Target Operation at the HERA-B Experiment

    SciTech Connect

    Vassiliev, Yu.; Aushev, V.; Ehret, K.; Funcke, M.; Sever, S.I.; Pavlenko, Yu.; Pugatch, V.; Spratte, S.; Symalla, M.; Tkatch, N.; Wegener, D.

    2000-12-31

    The HERA-B internal target consists of eight target ribbons arranged around the beam. Each target can be moved in the radial direction independently in sub-micron steps, allowing to compensate relative beam shifts and to steer for the desired interaction rate. The experimental constraints require a stable interaction rate equally distributed over all inserted targets. The actual equalization is based on a measurement of charge originated from the beam-target interaction. The system shows a good linearity with the interaction rate and allows a reasonable distribution of the interaction rate among several wires. To cross check the performance of the multi-wire steering, the reconstructed tracks and primary vertices in the silicon vertex detector were used.

  5. Xanthones from mangosteen (Garcinia mangostana): multi-targeting pharmacological properties.

    PubMed

    Jindarat, Sarawut

    2014-02-01

    This review focuses on mangosteen pericarp extracts, xanthones and derivatives for the future laboratory experiment and development in pharmacological aspects. All relevant literature databases were searched up to 2 March 2014. The search terms included mangosteen, xanthone, mangostin, and gatanin in all of the human, animal, in vitro and in vivo studies. Anti-intflammation, antioxidant, antibacterial, anticancer and antiulcer properties of each substance were the key parameters. Xanthones are a group of oxygen-containing heterocyclic compounds including alpha-mangostin, gamma-mangostin, mangosteen extract, xanthone derivatives and synthetic xanthones, which provide remarkable and diverse pharmacological effects such as anticancer, antioxidant, anti-inflammatory and antimicrobial activities. These xanthone compounds may play a major role in therapeutic treatment ofthe diseases but precise mechanisms ofaction are still unclear and needfurther investigation.

  6. [Multimorbidity and multi-target-therapy with herbal drugs].

    PubMed

    Saller, R; Rostock, M

    2012-12-12

    The active components of herbal drugs and substances are pleiotropic multi-ingredient compounds with multitarget properties including antiinflammatory effects. A pleiotropic inhibition of inflammation could play an important role in mutlimorbide patients as an attempt of prevention or retardation of metastasis. A large number of experimental data for European and non-European herbal drugs as well as various herbal drug combinations suggest such a possibility. Despite the so far small number of clinical studies, such an experimental herbal treatment could appear to be reasonable and acceptable, provided that there are data available on quality and safety of these herbal drugs by treatments of patients with various diseases. Besides, herbal drugs and substances play a growing role the treatment of patients with multimorbidity. Many of these herbal drugs have antiinflammatory effects beside their proved symptomatic efficacy in a lot of other diseases. The specific selection of herbal drugs that are efficacious in specific indications and additionally showed antiinflammatory effects offers the possibility of simultaneous antiinflammatory and specific efficacy. St. John's Wort and milk thistle belong to the oldest and to the best experimentally and clinically examined herbal remedies. The spectrum of internal and external uses of Hypercum perforatum as a multicompound herbal drug includes functional gastro-intestinal complaint and illness, skin disease, mucosal lesion, superficial injury, depressive upset and depression, somatoform disorders, restlessness, nervosity, convalescence, exhaustion and sleep disturbances respectively. The plurivalent character of the multicompound even enables a broad spectrum of activity. This might justify to prefer St. John's Wort to other drugs in a wide range of treatments: In multimorbide patients with depression or in depressive patients with coronary heart disease the anti-inflammatory effects could mean an additional advantage. However, at present there is still a great need and demand for therapy-oriented clinical research.

  7. 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.

  8. Multi-targeted prevention and therapy of cancer by proanthocyanidins.

    PubMed

    Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K

    2008-10-08

    In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual's everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anti-carcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-kappaB, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs.

  9. Multi-targeted prevention and therapy of cancer by proanthocyanidins

    PubMed Central

    Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K.

    2008-01-01

    In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual’s everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anticarcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-κB, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs. PMID:18457915

  10. Multi-Target Tracking for Swarm vs. Swarm UAV Systems

    DTIC Science & Technology

    2012-09-01

    coordinates. . . . . . 12 Figure 2.3 An illustration of geometric occlusion in generating detections. The red and blue agents (right) block portions of...according to the targets in the environments and uses Gaus- sian and uniform distributions. Both occlusions of the agents and possibilities for false...avoidance where they can cross over each other. Also agents have limited sensor coverage, and the effects of optical target occlusion is approximated in

  11. Review of Particle Properties

    NASA Astrophysics Data System (ADS)

    Hagiwara, K.; Hikasa, K.; Nakamura, K.; Tanabashi, M.; Aguilar-Benitez, M.; Amsler, C.; Barnett, R. M.; Burchat, P. R.; Carone, C. D.; Caso, C.; Conforto, G.; Dahl, O.; Doser, M.; Eidelman, S.; Feng, J. L.; Gibbons, L.; Goodman, M.; Grab, C.; Groom, D. E.; Gurtu, A.; Hayes, K. G.; Herna`Ndez-Rey, J. J.; Honscheid, K.; Kolda, C.; Mangano, M. L.; Manley, D. M.; Manohar, A. V.; March-Russell, J.; Masoni, A.; Miquel, R.; Mönig, K.; Murayama, H.; Navas, S.; Olive, K. A.; Pape, L.; Patrignani, C.; Piepke, A.; Roos, M.; Terning, J.; Törnqvist, N. A.; Trippe, T. G.; Vogel, P.; Wohl, C. G.; Workman, R. L.; Yao, W.-M.; Armstrong, B.; Gee, P. S.; Lugovsky, K. S.; Lugovsky, S. B.; Lugovsky, V. S.; Artuso, M.; Asner, D.; Babu, K. S.; Barberio, E.; Battaglia, M.; Bichsel, H.; Biebel, O.; Bloch, P.; Cahn, R. N.; Cattai, A.; Chivukula, R. S.; Cousins, R. D.; Cowan, G.; Damour, T.; Desler, K.; Donahue, R. J.; Edwards, D. A.; Elvira, V. D.; Erler, J.; Ezhela, V. V.; Fasso`, A.; Fetscher, W.; Fields, B. D.; Foster, B.; Froidevaux, D.; Fukugita, M.; Gaisser, T. K.; Garren, L.; Gerber, H.-J.; Gilman, F. J.; Haber, H. E.; Hagmann, C.; Hewett, J.; Hinchliffe, I.; Hogan, C. J.; Höhler, G.; Igo-Kemenes, P.; Jackson, J. D.; Johnson, K. F.; Karlen, D.; Kayser, B.; Klein, S. R.; Kleinknecht, K.; Knowles, I. G.; Kreitz, P.; Kuyanov, Yu. V.; Landua, R.; Langacker, P.; Littenberg, L.; Martin, A. D.; Nakada, T.; Narain, M.; Nason, P.; Peacock, J. A.; Quinn, H. R.; Raby, S.; Raffelt, G.; Razuvaev, E. A.; Renk, B.; Rolandi, L.; Ronan, M. T.; Rosenberg, L. J.; Sachrajda, C. T.; Sanda, A. I.; Sarkar, S.; Schmitt, M.; Schneider, O.; Scott, D.; Seligman, W. G.; Shaevitz, M. H.; Sjöstrand, T.; Smoot, G. F.; Spanier, S.; Spieler, H.; Spooner, N. J. C.; Srednicki, M.; Stahl, A.; Stanev, T.; Suzuki, M.; Tkachenko, N. P.; Valencia, G.; van Bibber, K.; Vincter, M. G.; Ward, D. R.; Webber, B. R.; Whalley, M.; Wolfenstein, L.; Womersley, J.; Woody, C. L.; Zenin, O. V.

    2002-07-01

    This biennial Review summarizes much of Particle Physics. Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations. For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review). Another new review is on Grand Unified Theories. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.

  12. Apparatus for measuring particle properties

    DOEpatents

    Rader, D.J.; Castaneda, J.N.; Grasser, T.W.; Brockmann, J.E.

    1998-08-11

    An apparatus is described for determining particle properties from detected light scattered by the particles. The apparatus uses a light beam with novel intensity characteristics to discriminate between particles that pass through the beam and those that pass through an edge of the beam. The apparatus can also discriminate between light scattered by one particle and light scattered by multiple particles. The particle`s size can be determined from the intensity of the light scattered. The particle`s velocity can be determined from the elapsed time between various intensities of the light scattered. 11 figs.

  13. Biomimetic particles as therapeutics.

    PubMed

    Meyer, Randall A; Sunshine, Joel C; Green, Jordan J

    2015-09-01

    In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

  14. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-01-01

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  15. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-09-02

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  16. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  17. Particle Physics Masterclass

    ScienceCinema

    Helio Takai

    2016-07-12

    Students from six local high schools -- Farmingdale, Sachem East, Shoreham, Smithtown East, Ward Melville, and William Floyd -- came to Brookhaven National Laboratory to experience research with particle physicist Helio Takai. They were among more than 6,

  18. Particle Pollution Designations

    EPA Pesticide Factsheets

    This area provides information on the process EPA, the states, and the tribes follow to designate areas as attainment (meeting) or nonattainment (not meeting) the particle pollution air quality standards.

  19. Elementary particle theory

    SciTech Connect

    Marciano, W.J.

    1984-12-01

    The present state of the art in elementary particle theory is reviewed. Topics include quantum electrodynamics, weak interactions, electroweak unification, quantum chromodynamics, and grand unified theories. 113 references. (WHK)

  20. Particle chemistry impactor experiment

    NASA Astrophysics Data System (ADS)

    Pueschel, R. F.; Snetsinger, K. G.; Ferry, G. V.; Goodman, J. K.; Verma, S.

    1990-01-01

    Polar stratospheric cloud (PSC) particles are collected on impactors and studied with regard to physical and chemical properties to help explain the importance of heterogeneous chemical reactions for stratospheric ozone depletion. The nitric, hydrochloric, and sulfuric acid content of stratospheric aerosol particles collected at 18 km altitude was determined. It is suggested that nitric acid is a component of polar stratospheric clouds. This is important for two reasons: (1) it proves that chlorine activation takes place at the surface of PSC particles by converting chemically inert chlorine nitrate to chlorine radicals that can react with ozone; and (2) if the PSC particles are large enough to settle out from the stratosphere, the possibility of nitric acid removal can result in the denitrification of the stratosphere.

  1. Research in particle theory

    SciTech Connect

    Mansouri, F.; Suranyi, P; Wijewardhana, L.C.R.

    1991-10-01

    In the test particle approximation, the scattering amplitude for two-particle scattering in (2+1)-dimensional Chern-Simons-Witten gravity and supergravity was computed and compared to the corresponding metric solutions. The formalism was then extended to the exact gauge theoretic treatment of the two-particle scattering problem and compared to 't Hooft's results from the metric approach. We have studied dynamical symmetry breaking in 2+1 dimensional field theories. We have analyzed strong Extended Technicolor (ETC) models where the ETC coupling is close to a critical value. There are effective scalar fields in each of the theories. We have worked our how such scalar particles can be produced and how they decay. The {phi}{sup 4} field theory was investigated in the Schrodinger representation. The critical behavior was extracted in an arbitrary number of dimensions in second order of a systematic truncation approximation. The correlation exponent agrees with known values within a few percent.

  2. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  3. Particle Physics Masterclass

    SciTech Connect

    Helio Takai

    2009-04-10

    Students from six local high schools -- Farmingdale, Sachem East, Shoreham, Smithtown East, Ward Melville, and William Floyd -- came to Brookhaven National Laboratory to experience research with particle physicist Helio Takai. They were among more than 6,

  4. Accelerating Particles with Plasma

    ScienceCinema

    Litos, Michael; Hogan, Mark

    2016-07-12

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  5. Elementary particle physics

    NASA Technical Reports Server (NTRS)

    Perkins, D. H.

    1986-01-01

    Elementary particle physics is discussed. Status of the Standard Model of electroweak and strong interactions; phenomena beyond the Standard Model; new accelerator projects; and possible contributions from non-accelerator experiments are examined.

  6. Particle Size Analysis.

    ERIC Educational Resources Information Center

    Barth, Howard G.; Sun, Shao-Tang

    1989-01-01

    Presents a review of research focusing on scattering, elution techniques, electrozone sensing, filtration, centrifugation, comparison of techniques, data analysis, and particle size standards. The review covers the period 1986-1988. (MVL)

  7. The packing of particles

    SciTech Connect

    Cumberland, D.J.; Crawford, R.J.

    1987-01-01

    The wide range of information currently available on the packing of particles is brought together in this monograph. The authors' interest in the subject was initially aroused by the question of whether there is an optimum particle size distribution which would maximise the packing density of particles - a question which has attracted the interest of scientists and engineers for centuries. The densification of a powder mass is of relevance in a great many industries, among them the pharmaceutical, ceramic, powder metallurgy and civil engineering industries. In addition, the packing of regular - or irregular - shaped particles is also of relevance to a surprisingly large number of other industries and subject areas, i.e. the foundry industry, nuclear engineering, chemical engineering, crystallography, geology, biology, telecommunications, and so on. Accordingly, this book is written for a wide audience.

  8. Electromagnetic particle simulation codes

    NASA Technical Reports Server (NTRS)

    Pritchett, P. L.

    1985-01-01

    Electromagnetic particle simulations solve the full set of Maxwell's equations. They thus include the effects of self-consistent electric and magnetic fields, magnetic induction, and electromagnetic radiation. The algorithms for an electromagnetic code which works directly with the electric and magnetic fields are described. The fields and current are separated into transverse and longitudinal components. The transverse E and B fields are integrated in time using a leapfrog scheme applied to the Fourier components. The particle pushing is performed via the relativistic Lorentz force equation for the particle momentum. As an example, simulation results are presented for the electron cyclotron maser instability which illustrate the importance of relativistic effects on the wave-particle resonance condition and on wave dispersion.

  9. Particle Size Analysis.

    ERIC Educational Resources Information Center

    Barth, Howard G.; Sun, Shao-Tang

    1989-01-01

    Presents a review of research focusing on scattering, elution techniques, electrozone sensing, filtration, centrifugation, comparison of techniques, data analysis, and particle size standards. The review covers the period 1986-1988. (MVL)

  10. Streams of Charged Particles

    NASA Image and Video Library

    2011-04-28

    This graphic shows the different streams of charged particles inside the bubble around our sun and outside, in the unexplored territory of interstellar space. The heliosheath, where NASA two Voyager spacecraft are now traveling, is shown in red.

  11. Particle chemistry impactor experiment

    NASA Technical Reports Server (NTRS)

    Pueschel, R. F.; Snetsinger, K. G.; Ferry, G. V.; Goodman, J. K.; Verma, S.

    1990-01-01

    Polar stratospheric cloud (PSC) particles are collected on impactors and studied with regard to physical and chemical properties to help explain the importance of heterogeneous chemical reactions for stratospheric ozone depletion. The nitric, hydrochloric, and sulfuric acid content of stratospheric aerosol particles collected at 18 km altitude was determined. It is suggested that nitric acid is a component of polar stratospheric clouds. This is important for two reasons: (1) it proves that chlorine activation takes place at the surface of PSC particles by converting chemically inert chlorine nitrate to chlorine radicals that can react with ozone; and (2) if the PSC particles are large enough to settle out from the stratosphere, the possibility of nitric acid removal can result in the denitrification of the stratosphere.

  12. Unstable particles near threshold

    NASA Astrophysics Data System (ADS)

    Chway, Dongjin; Jung, Tae Hyun; Kim, Hyung Do

    2016-07-01

    We explore the physics of unstable particles when the mother particle's mass is approximately the sum of the masses of its daughter particles. In this case, the conventional wave function renormalization factor used for the narrow width approximation is ill-defined. We propose a simple resolution of the problem that allows the use of the narrow width approximation by defining the wave function renormalization factor and the branching ratio in terms of the spectral density. We test new definitions by calculating the cross section in the Higgs portal model and a significant improvement is obtained. Meanwhile, no single decay width can be assigned to the unstable particles and non-exponential decay occurs at all time scales.

  13. Alpha-particle diagnostics

    SciTech Connect

    Young, K.M.

    1991-01-01

    This paper will focus on the state of development of diagnostics which are expected to provide the information needed for {alpha}- physics studies in the future. Conventional measurement of detailed temporal and spatial profiles of background plasma properties in DT will be essential for such aspects as determining heating effectiveness, shaping of the plasma profiles and effects of MHD, but will not be addressed here. This paper will address (1) the measurement of the neutron source, and hence {alpha}-particle birth profile, (2) measurement of the escaping {alpha}-particles and (3) measurement of the confined {alpha}-particles over their full energy range. There will also be a brief discussion of (4) the concerns about instabilities being generated by {alpha}-particles and the methods necessary for measuring these effects. 51 refs., 10 figs.

  14. Magnetic Particle Process Improvement

    SciTech Connect

    Hubert, R.R.

    2002-08-13

    The magnetic particle testing process is performed to find linear, surface and near surface discontinuities in ferromagnetic test materials. A wet fluorescent method is used at Honeywell Federal Manufacturing & Technologies (FM&T). This method employs a liquid carrier mixed with iron oxide particles in suspension, and the particles used in the method are coated with a fluorescent dye to make them visible under a black light. The process in its current state employs the use of a tank of liquid solution of a mineral oil carrier with iron oxide particles in suspension. The change to the use of an aerosol delivery system with the same material reduces the amount of waste involved in the process while preserving the sensitivity of the testing, shortens the flowtime for the test, and saves labor and material costs.

  15. Big Bang Day: 5 Particles - 5. The Next Particle

    ScienceCinema

    None

    2016-07-12

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 5. The Next Particle The "sparticle" - a super symmetric partner to all the known particles could be the answer to uniting all the known particles and their interactions under one grand theoretical pattern of activity. But how do researchers know where to look for such phenomena and how do they know if they find them? Simon Singh reviews the next particle that physicists would like to find if the current particle theories are to ring true.

  16. Big Bang Day: 5 Particles - 5. The Next Particle

    SciTech Connect

    2009-10-08

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 5. The Next Particle The "sparticle" - a super symmetric partner to all the known particles could be the answer to uniting all the known particles and their interactions under one grand theoretical pattern of activity. But how do researchers know where to look for such phenomena and how do they know if they find them? Simon Singh reviews the next particle that physicists would like to find if the current particle theories are to ring true.

  17. PARTICLES OF DIFFERENCE.

    SciTech Connect

    SCHWARTZ,S.E.

    2000-09-21

    It is no longer appropriate, if it ever was, to think of atmospheric aerosols as homogeneous spheres of uniform composition and size. Within the United States, and even more globally, not only the mass loading but also the composition, morphology, and size distribution of atmospheric aerosols are highly variable, as a function of location, and at a given location as a function of time. Particles of a given aerodynamic size may differ from one another, and even within individual particles material may be inhomogeneously distributed, as for example, carbon spherules imbedded in much larger sulfate particles. Some of the particulate matter is primary, that is, introduced into the atmosphere directly as particles, such as carbon particles in diesel exhaust. Some is secondary, that is, formed in the atmosphere by gas-to-particle conversion. Much of the material is inorganic, mainly sulfates and nitrates resulting mainly from energy-related emissions. Some of the material is carbonaceous, in part primary, in part secondary, and of this material some is anthropogenic and some biogenic. While the heterogeneity of atmospheric aerosols complicates the problem of understanding their loading and distribution, it may well be the key to its solution. By detailed examination of the materials comprising aerosols it is possible to infer the sources of these materials. It may be possible as well to identify specific health impairing agents. The heterogeneity of aerosol particles is thus the key to identifying their sources, to understanding the processes that govern their loading and properties, and to devising control strategies that are both effective and efficient. Future research must therefore take cognizance of differences among aerosol particles and use these differences to advantage.

  18. BRL Particle Sizing Interferometer

    DTIC Science & Technology

    1982-07-01

    and m" is the index of refraction. Thus, the same visibility function as for Class I particles still applies. However, the fringe period is scaled ...amplitudes of the probability density plot are relative. The largest amplitude is chosen to fit a convenient scale on the paper. The first column indicates...the numerical integration,it is difficult to discern or physically visualize the scaling laws which relate visibility to particle index-of-refraction

  19. PARTICLES OF DIFFERENCE.

    SciTech Connect

    SCHWARTZ,S.E.

    2000-09-21

    It is no longer appropriate, if it ever was, to think of atmospheric aerosols as homogeneous spheres of uniform composition and size. Within the United States, and even more globally, not only the mass loading but also the composition, morphology, and size distribution of atmospheric aerosols are highly variable, as a function of location, and at a given location as a function of time. Particles of a given aerodynamic size may differ from one another, and even within individual particles material may be inhomogeneously distributed, as for example, carbon spherules imbedded in much larger sulfate particles. Some of the particulate matter is primary, that is, introduced into the atmosphere directly as particles, such as carbon particles in diesel exhaust. Some is secondary, that is, formed in the atmosphere by gas-to-particle conversion. Much of the material is inorganic, mainly sulfates and nitrates resulting mainly from energy-related emissions. Some of the material is carbonaceous, in part primary, in part secondary, and of this material some is anthropogenic and some biogenic. While the heterogeneity of atmospheric aerosols complicates the problem of understanding their loading and distribution, it may well be the key to its solution. By detailed examination of the materials comprising aerosols it is possible to infer the sources of these materials. It may be possible as well to identify specific health impairing agents. The heterogeneity of aerosol particles is thus the key to identifying their sources, to understanding the processes that govern their loading and properties, and to devising control strategies that are both effective and efficient. Future research must therefore take cognizance of differences among aerosol particles and use these differences to advantage.

  20. The Least Particle Theory

    NASA Astrophysics Data System (ADS)

    Hartsock, Robert

    2011-10-01

    The Least Particle Theory states that the universe was cast as a great sea of energy. MaX Planck declared a quantum of energy to be the least value in the universe. We declare the quantum of energy to be the least particle in the universe. Stephen Hawking declared quantum mechanics to be of no value in todays gross mechanics. That's like saying the number 1 has no place in mathematics.

  1. Safe biodegradable fluorescent particles

    DOEpatents

    Martin, Sue I.; Fergenson, David P.; Srivastava, Abneesh; Bogan, Michael J.; Riot, Vincent J.; Frank, Matthias

    2010-08-24

    A human-safe fluorescence particle that can be used for fluorescence detection instruments or act as a safe simulant for mimicking the fluorescence properties of microorganisms. The particle comprises a non-biological carrier and natural fluorophores encapsulated in the non-biological carrier. By doping biodegradable-polymer drug delivery microspheres with natural or synthetic fluorophores, the desired fluorescence can be attained or biological organisms can be simulated without the associated risks and logistical difficulties of live microorganisms.

  2. ELEMENTARY PARTICLE INTERACTIONS

    SciTech Connect

    EFREMENKO, YURI; HANDLER, THOMAS; KAMYSHKOV, YURI; SIOPSIS, GEORGE; SPANIER, STEFAN

    2013-07-30

    The High-Energy Elementary Particle Interactions group at UT during the last three years worked on the following directions and projects: Collider-based Particle Physics; Neutrino Physics, particularly participation in “NOνA”, “Double Chooz”, and “KamLAND” neutrino experiments; and Theory, including Scattering amplitudes, Quark-gluon plasma; Holographic cosmology; Holographic superconductors; Charge density waves; Striped superconductors; and Holographic FFLO states.

  3. On Characterizing Particle Shape

    NASA Technical Reports Server (NTRS)

    Ennis, Bryan J.; Rickman, Douglas; Rollins, A. Brent; Ennis, Brandon

    2014-01-01

    It is well known that particle shape affects flow characteristics of granular materials, as well as a variety of other solids processing issues such as compaction, rheology, filtration and other two-phase flow problems. The impact of shape crosses many diverse and commercially important applications, including pharmaceuticals, civil engineering, metallurgy, health, and food processing. Two applications studied here include the dry solids flow of lunar simulants (e.g. JSC-1, NU-LHT-2M, OB-1), and the flow properties of wet concrete, including final compressive strength. A multi-dimensional generalized, engineering method to quantitatively characterize particle shapes has been developed, applicable to both single particle orientation and multi-particle assemblies. The two-dimension, three dimension inversion problem is also treated, and the application of these methods to DEM model particles will be discussed. In the case of lunar simulants, flow properties of six lunar simulants have been measured, and the impact of particle shape on flowability - as characterized by the shape method developed here -- is discussed, especially in the context of three simulants of similar size range. In the context of concrete processing, concrete construction is a major contributor to greenhouse gas production, of which the major contributor is cement binding loading. Any optimization in concrete rheology and packing that can reduce cement loading and improve strength loading can also reduce currently required construction safety factors. The characterization approach here is also demonstrated for the impact of rock aggregate shape on concrete slump rheology and dry compressive strength.

  4. Statistics of indistinguishable particles.

    PubMed

    Wittig, Curt

    2009-07-02

    The wave function of a system containing identical particles takes into account the relationship between a particle's intrinsic spin and its statistical property. Specifically, the exchange of two identical particles having odd-half-integer spin results in the wave function changing sign, whereas the exchange of two identical particles having integer spin is accompanied by no such sign change. This is embodied in a term (-1)(2s), which has the value +1 for integer s (bosons), and -1 for odd-half-integer s (fermions), where s is the particle spin. All of this is well-known. In the nonrelativistic limit, a detailed consideration of the exchange of two identical particles shows that exchange is accompanied by a 2pi reorientation that yields the (-1)(2s) term. The same bookkeeping is applicable to the relativistic case described by the proper orthochronous Lorentz group, because any proper orthochronous Lorentz transformation can be expressed as the product of spatial rotations and a boost along the direction of motion.

  5. Particle Accelerators Test Cosmological Theory.

    ERIC Educational Resources Information Center

    Schramm, David N.; Steigman, Gary

    1988-01-01

    Discusses the symbiotic relationship of cosmology and elementary-particle physics. Presents a brief overview of particle physics. Explains how cosmological considerations set limits on the number of types of elementary particles. (RT)

  6. Particle Accelerators Test Cosmological Theory.

    ERIC Educational Resources Information Center

    Schramm, David N.; Steigman, Gary

    1988-01-01

    Discusses the symbiotic relationship of cosmology and elementary-particle physics. Presents a brief overview of particle physics. Explains how cosmological considerations set limits on the number of types of elementary particles. (RT)

  7. Particle segregation during explosive dispersal of binary particle mixtures

    NASA Astrophysics Data System (ADS)

    Frost, David L.; Loiseau, Jason; Marr, Bradley J.; Goroshin, Samuel

    2017-01-01

    The explosive dispersal of a layer of solid particles surrounding a spherical high explosive charge generates a turbulent, multiphase flow. The shock-compacted particle layer typically fractures into discrete fragments which move radially outwards on ballistic trajectories. The fragments shed particles in their wakes forming jet-like structures. The tendency to form jets depends on the mass-ratio of the particles to explosive and the type of particles. Brittle or soft, ductile particles are more susceptible to forming jets during compaction and dispersal, whereas particles that are comprised of material with moderate hardness, high compressive strength and high toughness are much less prone to forming jets. Experiments have been carried out to determine the degree of particle segregation that occurs during the explosive dispersal of a uniform, binary mixture containing both "jetting" (silicon carbide) and "non-jetting" (steel) particles with various mass fractions of each particle type. During the dispersal of mixtures that contain predominantly non-jetting (steel) particles, the steel particles form a stable layer whereas the jetting (silicon carbide) particles rapidly segregate and form jets which are confined within the shell of steel particles. As the fraction of silicon carbide particles increases, the jet structures dominate the particle motion and the steel particles are entrained into the jet structures.

  8. Tortuosity of porous particles.

    PubMed

    Barrande, M; Bouchet, R; Denoyel, R

    2007-12-01

    Tortuosity is often used as an adjustable parameter in models of transfer properties through porous media. This parameter, not reducible to classical measured microstructural parameters like specific surface area, porosity, or pore size distribution, reflects the efficiency of percolation paths, which is linked to the topology of the material. The measurement of the effective conductivity of a bed of particles saturated with an electrolyte is a simple way to evaluate tortuosity. Nevertheless, it received only little attention because of the real difficulties in both getting reliable results and interpreting data. Notably, the discrimination between the contribution of interparticle and intraparticle porosities to the tortuosity is not resolved. To our knowledge, there is no model able to fit the experimental data of the tortuosity of a suspension, and a fortiori of a particle bed, in the whole porosity range. Only empirical expressions have been proposed, but they do not allow deriving intratortuosity of a porous particle. For a dilute system, Maxwell's equation predicts the effective conductivity of suspensions of spherical particles as a function of the bulk electrolyte conductivity and of particle conductivity. The intraparticle tortuosity can be derived from the particle conductivity obtained from the Maxwell equation applied to data at infinite dilution of particles. Then, by assuming that the Maxwell equation is a first-order approximation of the conductivity as a function of porosity, we propose an explicit relation of the tortuosity tau of a suspension of porous particles, obtained by conductivity measurement, as tau = tau(epsilon, epsilon(p), tau(p)), where epsilon is the total porosity of the suspension, tau(p) is the intraparticle tortuosity, and epsilon(p) is the particle porosity. This relationship fits the experimental data in the whole porosity range and can be used to determine tau(p) from an experiment at only one porosity. Finally, the obtained

  9. System for forming janus particles

    DOEpatents

    Hong, Liang [Midland, MI; Jiang, Shan [Champaign, IL; Granick, Steve [Champaign, IL

    2011-01-25

    The invention is a method of forming Janus particles, that includes forming an emulsion that contains initial particles, a first liquid, and a second liquid; solidifying the first liquid to form a solid that contains at least a portion of the initial particles on a surface of the solid; and treating the exposed particle sides with a first surface modifying agent, to form the Janus particles. Each of the initial particles on the surface has an exposed particle side and a blocked particle side.

  10. Proton: the particle.

    PubMed

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

  11. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and

  12. Alpha-particle microdosimetry.

    PubMed

    Chouin, Nicolas; Bardies, Manuel

    2011-07-01

    With the increasing availability of alpha emitters, targeted α-particle therapy has emerged as a solution of choice to treat haematological cancers and micrometastatic and minimal residual diseases. Alpha-particles are highly cytotoxic because of their high linear energy transfer (LET) and have a short range of a few cell diameters in tissue, assuring good treatment specificity. These radiologic features make conventional dosimetry less relevant for that context. Stochastic variations in the energy deposited in cell nuclei are important because of the microscopic target size, low number of α- particle traversals, and variation in LET along the α-particle track. Microdosimetry provides a conceptual framework that aims at a systematic analysis of the stochastic distribution of energy deposits in irradiated matter. The different quantities of microdosimetry and the different methods of microdosimetric calculations were described in the early eighties. Since then, numerous models have been published through the years and applied to analyse experimental data or to model realistic therapeutic situations. Major results have been an accurate description of the high toxicity of α-particles, and the description of the predominant effect of activity distribution at the cellular scale on toxicity or efficacy of potential targeted α-particle therapies. This last factor represents a major limitation to the use of microdosimetry in vivo because determination of the source - target distribution is complicated. The future contributions of microdosimetry in targeted α-particle therapy research will certainly depend on the ability to develop high-resolution detectors and on the implementation of pharmaco-kinetic models at the tumour microenvironment scale.

  13. Proton: The Particle

    SciTech Connect

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10{sup 80}. Protons were created at 10{sup −6} –1 second after the Big Bang at ≈1.37 × 10{sup 10} years beforethe present. Proton life span has been experimentally determined to be ≥10{sup 34} years; that is, the age of the universe is 10{sup −24}th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W{sup +}, W{sup −}, Z{sup 0}, and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

  14. A relationship between maximum packing of particles and particle size

    NASA Technical Reports Server (NTRS)

    Fedors, R. F.

    1979-01-01

    Experimental data indicate that the volume fraction of particles in a packed bed (i.e. maximum packing) depends on particle size. One explanation for this is based on the idea that particle adhesion is the primary factor. In this paper, however, it is shown that entrainment and immobilization of liquid by the particles can also account for the facts.

  15. Review of Particle Physics

    NASA Astrophysics Data System (ADS)

    Olive, K. A.; Particle Data Group; et al.

    2016-10-01

    The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. Contents Abstract, Contributors, Highlights and Table of ContentsAcrobat PDF (150 KB) IntroductionAcrobat PDF (456 KB) Particle Physics Summary Tables Gauge and Higgs bosonsAcrobat PDF (155 KB) LeptonsAcrobat PDF (134 KB) QuarksAcrobat PDF (84 KB) MesonsAcrobat PDF (871 KB) BaryonsAcrobat PDF (300 KB) Searches (Supersymmetry, Compositeness, etc.)Acrobat PDF (91 KB) Tests of conservation lawsAcrobat PDF (330 KB) Reviews, Tables, and Plots Detailed contents for this sectionAcrobat PDF (37 KB) Constants, Units, Atomic and Nuclear PropertiesAcrobat PDF (278 KB) Standard Model and Related TopicsAcrobat PDF (7.3 MB) Astrophysics and CosmologyAcrobat PDF (2.7 MB) Experimental Methods and CollidersAcrobat PDF (3.8 MB) Mathematical Tools or Statistics, Monte Carlo, Group

  16. Review of Particle Physics

    NASA Astrophysics Data System (ADS)

    Patrignani, C.; Particle Data Group

    2016-10-01

    The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. Contents Abstract, Contributors, Highlights and Table of ContentsAcrobat PDF (150 KB) IntroductionAcrobat PDF (456 KB) Particle Physics Summary Tables Gauge and Higgs bosonsAcrobat PDF (155 KB) LeptonsAcrobat PDF (134 KB) QuarksAcrobat PDF (84 KB) MesonsAcrobat PDF (871 KB) BaryonsAcrobat PDF (300 KB) Searches (Supersymmetry, Compositeness, etc.)Acrobat PDF (91 KB) Tests of conservation lawsAcrobat PDF (330 KB) Reviews, Tables, and Plots Detailed contents for this sectionAcrobat PDF (37 KB) Constants, Units, Atomic and Nuclear PropertiesAcrobat PDF (278 KB) Standard Model and Related TopicsAcrobat PDF (7.3 MB) Astrophysics and CosmologyAcrobat PDF (2.7 MB) Experimental Methods and CollidersAcrobat PDF (3.8 MB) Mathematical Tools or Statistics, Monte Carlo, Group

  17. Particle physics and cosmology

    SciTech Connect

    Kolb, E.W.

    1986-10-01

    This series of lectures is about the role of particle physics in physical processes that occurred in the very early stages of the bug gang. Of particular interest is the role of particle physics in determining the evolution of the early Universe, and the effect of particle physics on the present structure of the Universe. The use of the big bang as a laboratory for placing limits on new particle physics theories will also be discussed. Section 1 reviews the standard cosmology, including primordial nucleosynthesis. Section 2 reviews the decoupling of weakly interacting particles in the early Universe, and discusses neutrino cosmology and the resulting limits that may be placed on the mass and lifetime of massive neutrinos. Section 3 discusses the evolution of the vacuum through phase transitions in the early Universe and the formation of topological defects in the transitions. Section 4 covers recent work on the generation of the baryon asymmetry by baryon-number violating reactions in Grand Unified Theories, and mentions some recent work on baryon number violation effects at the electroweak transition. Section 5 is devoted to theories of cosmic inflation. Finally, Section 6 is a discussion of the role of extra spatial dimensions in the evolution of the early Universe. 78 refs., 32 figs., 6 tabs.

  18. Cosmology and Particle Physics

    NASA Astrophysics Data System (ADS)

    Steigman, G.

    1982-01-01

    The cosmic connections between physics on the very largest and very smallest scales are reviewed with an emphasis on the symbiotic relation between elementary particle physics and cosmology. After a review of the early Universe as a cosmic accelerator, various cosmological and astrophysical constraints on models of particle physics are outlined. To illustrate this approach to particle physics via cosmology, reference is made to several areas of current research: baryon non-conservation and baryon asymmetry; free quarks, heavy hadrons and other exotic relics; primordial nucleosynthesis and neutrino masses. In the last few years we have witnessed the birth and growth to healthy adolescence of a new collaboration between astrophysicists and particle physicists. The most notable success of this cooperative effort has been to provide the framework for understanding, within the context of GUTs and the hot big-bang cosmology, the universal baryon asymmetry. The most exciting new predictions this effort has spawned are that exotic relics may exist in detectable abundances. In particular, we may live in a neutrino-dominated Universe. In the next few years, accummulating laboratory data (for example proton decay, neutrino masses and oscillations) coupled with theoritical work in particle physics and cosmology will ensure the growth to maturity of this joint effort.

  19. Energetic Particles Investigation (EPI)

    NASA Astrophysics Data System (ADS)

    Fischer, H. M.; Mihalov, J. D.; Lanzerotti, L. J.; Wibberenz, G.; Rinnert, K.; Gliem, F. O.; Bach, J.

    1992-05-01

    The EPI instrument operates during the pre-entry phase of the Galileo Probe. The main objective is the study of the energetic particle population in the inner Jovian magnetosphere and in the upper atmosphere. This will be achieved through omnidirectional measurements of electrons, protons, alpha-particles and heavy ions (Z greater than 2) and recording intensity profiles with a spatial resolution of about 0.02 Jupiter radii. Sectored data will also be obtained for electrons, protons, and alpha-particles to determine directional anisotropies and particle pitch angle distributions. The detector assembly is a two-element telescope using totally depleted circular silicon surface-barrier detectors surrounded by cylindrical tungsten shielding. The lower energy threshold of the particle species investigated during the Probe's pre-entry phase is determined by the material thickness of the Probe's rear heat shield which is required for heat protection of the scientific payload during entry into the Jovian atmosphere. The EPI instrument is combined with the Lightning and Radio Emission Detector and both instruments share one interface of the Probe's power, command, and data unit.

  20. RESONATOR PARTICLE SEPARATOR

    DOEpatents

    Blewett, J.P.

    1962-01-01

    A wave guide resonator structure is described for use in separating particles of equal momentum but differing in mass and having energies exceeding one billion electron volts. The particles are those of sub-atomic size and are generally produced as a result of the bombardment of a target by a beam such as protons produced in a high-energy accelerator. In this wave guide construction, the particles undergo preferential deflection as a result of the presence of an electric field. The boundary conditions established in the resonator are such as to eliminate an interfering magnetic component, and to otherwise phase the electric field to obtain a traveling wave such as one which moves at the same speed as the unwanted particle. The latter undergoes continuous deflection over the whole length of the device and is, therefore, eliminated while the wanted particle is deflected in opposite directions over the length of the resonator and is thus able to enter an exit aperture. (AEC)

  1. Large Particle Titanate Sorbents

    SciTech Connect

    Taylor-Pashow, K.

    2015-10-08

    This research project was aimed at developing a synthesis technique for producing large particle size monosodium titanate (MST) to benefit high level waste (HLW) processing at the Savannah River Site (SRS). Two applications were targeted, first increasing the size of the powdered MST used in batch contact processing to improve the filtration performance of the material, and second preparing a form of MST suitable for deployment in a column configuration. Increasing the particle size should lead to improvements in filtration flux, and decreased frequency of filter cleaning leading to improved throughput. Deployment of MST in a column configuration would allow for movement from a batch process to a more continuous process. Modifications to the typical MST synthesis led to an increase in the average particle size. Filtration testing on dead-end filters showed improved filtration rates with the larger particle material; however, no improvement in filtration rate was realized on a crossflow filter. In order to produce materials suitable for column deployment several approaches were examined. First, attempts were made to coat zirconium oxide microspheres (196 µm) with a layer of MST. This proved largely unsuccessful. An alternate approach was then taken synthesizing a porous monolith of MST which could be used as a column. Several parameters were tested, and conditions were found that were able to produce a continuous structure versus an agglomeration of particles. This monolith material showed Sr uptake comparable to that of previously evaluated samples of engineered MST in batch contact testing.

  2. DMSwarm: Particles in PETSc

    NASA Astrophysics Data System (ADS)

    May, Dave A.; Knepley, Matthew G.

    2017-04-01

    Whilst specific details of particle methods are as diverse as the applications in which they are utilized within, such methods have a number of common requirements. Specifically these entail: the need to attach data (or fields) to each point; support for the advection of points within some domain; dynamic insertion and deletion of points; collection type operations to gather nearby points; and methods to interpolate and restrict data back and forth between a set of points and a background mesh. Despite the commonality of these requirements, to date, few computational libraries provide high level support for particle methods in either a sequential, or parallel (MPI) computing environment. In this presentation, we describe the recently introduced implementation DMSwarm within the Portable, Extensible Toolkit for Scientific computing (PETSc) which provides a fully parallel solution for pure particle methods (e.g. DEM, SPH, EFG) and for particle-mesh methods (e.g. PIC, FLIP, MPM, GIMP). Particle-In-Cell (PIC) methods with geodynamic simulation tools are ubiquitous. To illustrate the functionality provided by DMSwarm, we present results from viscous flow calculations using a finite element PIC method applied to study Rayleigh-Taylor instabilities using both structured and unstructured meshes. Our results are derived from standard examples provided with the PETSc source distribution and serve as an entry-point for new users to learn how to incorporate DMSwarm into their geodynamic software.

  3. Lorentz force particle analyzer

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Thess, André; Moreau, René; Tan, Yanqing; Dai, Shangjun; Tao, Zhen; Yang, Wenzhi; Wang, Bo

    2016-07-01

    A new contactless technique is presented for the detection of micron-sized insulating particles in the flow of an electrically conducting fluid. A transverse magnetic field brakes this flow and tends to become entrained in the flow direction by a Lorentz force, whose reaction force on the magnetic-field-generating system can be measured. The presence of insulating particles suspended in the fluid produce changes in this Lorentz force, generating pulses in it; these pulses enable the particles to be counted and sized. A two-dimensional numerical model that employs a moving mesh method demonstrates the measurement principle when such a particle is present. Two prototypes and a three-dimensional numerical model are used to demonstrate the feasibility of a Lorentz force particle analyzer (LFPA). The findings of this study conclude that such an LFPA, which offers contactless and on-line quantitative measurements, can be applied to an extensive range of applications. These applications include measurements of the cleanliness of high-temperature and aggressive molten metal, such as aluminum and steel alloys, and the clean manufacturing of semiconductors.

  4. Big Bang Day: 5 Particles - 3. The Anti-particle

    ScienceCinema

    None

    2016-07-12

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 3. The Anti-particle. It appears to be the stuff of science fiction. Associated with every elementary particle is an antiparticle which has the same mass and opposite charge. Should the two meet and combine, the result is annihilation - and a flash of light. Thanks to mysterious processes that occurred after the Big Bang there are a vastly greater number of particles than anti-particles. So how could their elusive existence be proved? At CERN particle physicists are crashing together subatomic particles at incredibly high speeds to create antimatter, which they hope will finally reveal what happened at the precise moment of the Big Bang to create the repertoire of elementary particles and antiparticles in existence today.

  5. Big Bang Day: 5 Particles - 3. The Anti-particle

    SciTech Connect

    2009-10-07

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 3. The Anti-particle. It appears to be the stuff of science fiction. Associated with every elementary particle is an antiparticle which has the same mass and opposite charge. Should the two meet and combine, the result is annihilation - and a flash of light. Thanks to mysterious processes that occurred after the Big Bang there are a vastly greater number of particles than anti-particles. So how could their elusive existence be proved? At CERN particle physicists are crashing together subatomic particles at incredibly high speeds to create antimatter, which they hope will finally reveal what happened at the precise moment of the Big Bang to create the repertoire of elementary particles and antiparticles in existence today.

  6. Charged particle accelerator grating

    DOEpatents

    Palmer, R.B.

    1985-09-09

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator is described. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams onto the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  7. Carbon-particle generator

    DOEpatents

    Hunt, A.J.

    1982-09-29

    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.

  8. Precision wood particle feedstocks

    DOEpatents

    Dooley, James H; Lanning, David N

    2013-07-30

    Wood particles having fibers aligned in a grain, wherein: the wood particles are characterized by a length dimension (L) aligned substantially parallel to the grain, a width dimension (W) normal to L and aligned cross grain, and a height dimension (H) normal to W and L; the L.times.H dimensions define two side surfaces characterized by substantially intact longitudinally arrayed fibers; the W.times.H dimensions define two cross-grain end surfaces characterized individually as aligned either normal to the grain or oblique to the grain; the L.times.W dimensions define two substantially parallel top and bottom surfaces; and, a majority of the W.times.H surfaces in the mixture of wood particles have end checking.

  9. Particle fuel bed tests

    SciTech Connect

    Horn, F.L.; Powell, J.R.; Savino, J.M.

    1985-01-01

    Gas-cooled reactors, using packed beds of small diameter coated fuel particles have been proposed for compact, high-power systems. The particulate fuel used in the tests was 800 microns in diameter, consisting of a thoria kernel coated with 200 microns of pyrocarbon. Typically, the bed of fuel particles was contained in a ceramic cylinder with porous metallic frits at each end. A dc voltage was applied to the metallic frits and the resulting electric current heated the bed. Heat was removed by passing coolant (helium or hydrogen) through the bed. Candidate frit materials, rhenium, nickel, zirconium carbide, and zirconium oxide were unaffected, while tungsten and tungsten-rhenium lost weight and strength. Zirconium-carbide particles were tested at 2000 K in H/sub 2/ for 12 hours with no visible reaction or weight loss.

  10. On particle track detectors

    NASA Technical Reports Server (NTRS)

    Benton, E. V.; Gruhn, T. A.; Andrus, C. H.

    1973-01-01

    Aqueous sodium hydroxide is widely used to develop charged particle tracks in polycarbonate film, particularly Lexan. The chemical nature of the etching process for this system has been determined. A method employing ultra-violet absorbance was developed for monitoring the concentration of the etch products in solution. Using this method it was possible to study the formation of the etching solution saturated in etch products. It was found that the system super-saturates to a significant extent before precipitation occurs. It was also learned that the system approaches its equilibrium state rather slowly. It is felt that both these phenomena may be due to the presence of surfactant in the solution. In light of these findings, suggestions are given regarding the preparation and maintenance of the saturated etch solution. Two additional research projects, involving automated techniques for particle track analysis and particle identification using AgCl crystals, are briefly summarized.

  11. Interplanetary particle beams

    NASA Technical Reports Server (NTRS)

    Dulk, G. A.

    1990-01-01

    This paper reviews observations of interplanetary particle beams of the kind that frequently accompany a solar flare. It is shown that the most frequently observed beams are beams of electrons which are associated with radio bursts of type III, but occasionally with flares and X-ray bursts. Although the main features of these beams and their associated plasma waves and radio bursts are known, uncertainties remain in terms of the correlation between electron beams and filamentary structures, the relative importance of the quasi-linear and the nonlinear wave emissions as the dominant process, and the mechanism of conversion of some of the Langmuir wave energy into radio emissions. Other particle beams discussed are those composed of protons, neutrons, He ions, or heavy ions. While most of these beams originate from sun flares, the source of some of particle beams may be the earth, Jupiter, or other planets as well as comets.

  12. Moving particle composition analyzer

    NASA Technical Reports Server (NTRS)

    Auer, S. O. (Inventor)

    1976-01-01

    A mass spectrometry apparatus for analyzing the composition of moving microscopic particles is introduced. The apparatus includes a capacitor with a front electrode upon which the particles impinge, a back electrode, and a solid dielectric sandwiched between the front and back electrodes. In one embodiment, the electrodes and dielectric are arcuately shaped as concentric peripheral segments of different spheres having a common center and different radii. The front electrode and dielectric together have a thickness such that an impinging particle can penetrate them. In a second embodiment, the capacitor has planar, parallel electrodes, in which case the ejected positive ions are deflected downstream of a planar grid by a pair of spaced, arcuate capacitor plates having a region between them through which the ejected ions travel.

  13. Biological particle identification apparatus

    DOEpatents

    Salzman, Gary C.; Gregg, Charles T.; Grace, W. Kevin; Hiebert, Richard D.

    1989-01-01

    An apparatus and method for making multiparameter light scattering measurements from suspensions of biological particles is described. Fourteen of the sixteen Mueller matrix elements describing the particles under investigation can be substantially individually determined as a function of scattering angle and probing radiations wavelength, eight elements simultaneously for each of two apparatus configurations using an apparatus which incluees, in its simplest form, two polarization modulators each operating at a chosen frequency, one polarizer, a source of monochromatic electromagnetic radiation, a detector sensitive to the wavelength of radiation employed, eight phase-sensitive detectors, and appropriate electronics. A database of known biological particle suspensions can be assembled, and unknown samples can be quickly identified once measurements are performed on it according to the teachings of the subject invention, and a comparison is made with the database.

  14. Perspective: Dissipative particle dynamics

    NASA Astrophysics Data System (ADS)

    Español, Pep; Warren, Patrick B.

    2017-04-01

    Dissipative particle dynamics (DPD) belongs to a class of models and computational algorithms developed to address mesoscale problems in complex fluids and soft matter in general. It is based on the notion of particles that represent coarse-grained portions of the system under study and allow, therefore, reaching time and length scales that would be otherwise unreachable from microscopic simulations. The method has been conceptually refined since its introduction almost twenty five years ago. This perspective surveys the major conceptual improvements in the original DPD model, along with its microscopic foundation, and discusses outstanding challenges in the field. We summarize some recent advances and suggest avenues for future developments.

  15. Incompressible smoothed particle hydrodynamics

    SciTech Connect

    Ellero, Marco Serrano, Mar; Espanol, Pep

    2007-10-01

    We present a smoothed particle hydrodynamic model for incompressible fluids. As opposed to solving a pressure Poisson equation in order to get a divergence-free velocity field, here incompressibility is achieved by requiring as a kinematic constraint that the volume of the fluid particles is constant. We use Lagrangian multipliers to enforce this restriction. These Lagrange multipliers play the role of non-thermodynamic pressures whose actual values are fixed through the kinematic restriction. We use the SHAKE methodology familiar in constrained molecular dynamics as an efficient method for finding the non-thermodynamic pressure satisfying the constraints. The model is tested for several flow configurations.

  16. Piezoelectric particle accelerator

    DOEpatents

    Kemp, Mark A.; Jongewaard, Erik N.; Haase, Andrew A.; Franzi, Matthew

    2017-08-29

    A particle accelerator is provided that includes a piezoelectric accelerator element, where the piezoelectric accelerator element includes a hollow cylindrical shape, and an input transducer, where the input transducer is disposed to provide an input signal to the piezoelectric accelerator element, where the input signal induces a mechanical excitation of the piezoelectric accelerator element, where the mechanical excitation is capable of generating a piezoelectric electric field proximal to an axis of the cylindrical shape, where the piezoelectric accelerator is configured to accelerate a charged particle longitudinally along the axis of the cylindrical shape according to the piezoelectric electric field.

  17. Perspective: Dissipative particle dynamics.

    PubMed

    Español, Pep; Warren, Patrick B

    2017-04-21

    Dissipative particle dynamics (DPD) belongs to a class of models and computational algorithms developed to address mesoscale problems in complex fluids and soft matter in general. It is based on the notion of particles that represent coarse-grained portions of the system under study and allow, therefore, reaching time and length scales that would be otherwise unreachable from microscopic simulations. The method has been conceptually refined since its introduction almost twenty five years ago. This perspective surveys the major conceptual improvements in the original DPD model, along with its microscopic foundation, and discusses outstanding challenges in the field. We summarize some recent advances and suggest avenues for future developments.

  18. Wear Particle Atlas. Revised

    DTIC Science & Technology

    1982-06-28

    Nonferrous Metals 27 1.6.2 Copper Alloys 28 1.6.3 Lead /Tin Alloys 32 1,"( Ferrous Oxides 33 1.7.1 Red Oxides of Iron 33 1.7.2 Black...exit end of the ferrogram. Ferrous (magnetic) particles are deposited in strings which follow the field lines of the magnet assembly positioned ueiow...particularly useful in research where it is desired to photograph assemblies of particles requiring a large depth of focus. However, the SEM shows only

  19. Amorphous silicon ionizing particle detectors

    DOEpatents

    Street, Robert A.; Mendez, Victor P.; Kaplan, Selig N.

    1988-01-01

    Amorphous silicon ionizing particle detectors having a hydrogenated amorphous silicon (a--Si:H) thin film deposited via plasma assisted chemical vapor deposition techniques are utilized to detect the presence, position and counting of high energy ionizing particles, such as electrons, x-rays, alpha particles, beta particles and gamma radiation.

  20. Amorphous silicon ionizing particle detectors

    DOEpatents

    Street, R.A.; Mendez, V.P.; Kaplan, S.N.

    1988-11-15

    Amorphous silicon ionizing particle detectors having a hydrogenated amorphous silicon (a--Si:H) thin film deposited via plasma assisted chemical vapor deposition techniques are utilized to detect the presence, position and counting of high energy ionizing particles, such as electrons, x-rays, alpha particles, beta particles and gamma radiation. 15 figs.

  1. Apparatus for measuring particle properties

    DOEpatents

    Rader, Daniel J.; Castaneda, Jaime N.; Grasser, Thomas W.; Brockmann, John E.

    1998-01-01

    An apparatus for determining particle properties from detected light scattered by the particles. The apparatus uses a light beam with novel intensity characteristics to discriminate between particles that pass through the beam and those that pass through an edge of the beam. The apparatus can also discriminate between light scattered by one particle and light scattered by multiple particles. The particle's size can be determined from the intensity of the light scattered. The particle's velocity can be determined from the elapsed time between various intensities of the light scattered.

  2. Insights into Particle Cycling from Thorium and Particle Data

    NASA Astrophysics Data System (ADS)

    Lam, Phoebe J.; Marchal, Olivier

    2015-01-01

    Marine particles are a main vector by which the biological carbon pump in the ocean transfers carbon from the atmosphere to the deep ocean. Marine particles exist in a continuous spectrum of sizes, but they can be functionally grouped into a small, suspended class (which constitutes most of the total particle mass) and a large, sinking class (which contributes most of the particle flux). These two classes are connected by aggregation and disaggregation processes. The interplay of processes that create, aggregate, and destroy marine particles determines the strength and transfer efficiency of the biological pump. Measurements of radiocarbon, barium, and organic biomarkers on suspended and sinking particles have provided qualitative insights into particle dynamics, and measurements of thorium isotopes have provided quantitative estimates of rates. Here, we review what has been learned so far about particle dynamics in the ocean from chemical measurements on suspended and sinking particles. We then discuss future directions for this approach.

  3. Insights into particle cycling from thorium and particle data.

    PubMed

    Lam, Phoebe J; Marchal, Olivier

    2015-01-01

    Marine particles are a main vector by which the biological carbon pump in the ocean transfers carbon from the atmosphere to the deep ocean. Marine particles exist in a continuous spectrum of sizes, but they can be functionally grouped into a small, suspended class (which constitutes most of the total particle mass) and a large, sinking class (which contributes most of the particle flux). These two classes are connected by aggregation and disaggregation processes. The interplay of processes that create, aggregate, and destroy marine particles determines the strength and transfer efficiency of the biological pump. Measurements of radiocarbon, barium, and organic biomarkers on suspended and sinking particles have provided qualitative insights into particle dynamics, and measurements of thorium isotopes have provided quantitative estimates of rates. Here, we review what has been learned so far about particle dynamics in the ocean from chemical measurements on suspended and sinking particles. We then discuss future directions for this approach.

  4. Elementary Particles and Forces.

    ERIC Educational Resources Information Center

    Quigg, Chris

    1985-01-01

    Discusses subatomic particles (quarks, leptons, and others) revealed by higher accelerator energies. A connection between forces at this subatomic level has been established, and prospects are good for a description of forces that encompass binding atomic nuclei. Colors, fundamental interactions, screening, camouflage, electroweak symmetry, and…

  5. Lunar Soil Particle Separator

    NASA Technical Reports Server (NTRS)

    Berggren, Mark

    2010-01-01

    The Lunar Soil Particle Separator (LSPS) beneficiates soil prior to in situ resource utilization (ISRU). It can improve ISRU oxygen yield by boosting the concentration of ilmenite, or other iron-oxide-bearing materials found in lunar soils, which can substantially reduce hydrogen reduction reactor size, as well as drastically decreasing the power input required for soil heating

  6. Supertwistors and massive particles

    SciTech Connect

    Mezincescu, Luca; Routh, Alasdair J.; Townsend, Paul K.

    2014-07-15

    In the (super)twistor formulation of massless (super)particle mechanics, the mass-shell constraint is replaced by a “spin-shell” constraint from which the spin content can be read off. We extend this formalism to massive (super)particles (with N-extended space–time supersymmetry) in three and four space–time dimensions, explaining how the spin-shell constraints are related to spin, and we use it to prove equivalence of the massive N=1 and BPS-saturated N=2 superparticle actions. We also find the supertwistor form of the action for “spinning particles” with N-extended worldline supersymmetry, massless in four dimensions and massive in three dimensions, and we show how this simplifies special features of the N=2 case. -- Highlights: •Spin-shell constraints are related to Poincaré Casimirs. •Twistor form of 4D spinning particle for spin N/2. •Twistor proof of scalar/antisymmetric tensor equivalence for 4D spin 0. •Twistor form of 3D particle with arbitrary spin. •Proof of equivalence of N=1 and N=2 BPS massive 4D superparticles.

  7. Smoothed Particle Hydrodynamic Simulator

    SciTech Connect

    2016-10-05

    This code is a highly modular framework for developing smoothed particle hydrodynamic (SPH) simulations running on parallel platforms. The compartmentalization of the code allows for rapid development of new SPH applications and modifications of existing algorithms. The compartmentalization also allows changes in one part of the code used by many applications to instantly be made available to all applications.

  8. Nucleosome Core Particle

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Nucleosome Core Particle grown on STS-81. The fundamental structural unit of chromatin and is the basis for organization within the genome by compaction of DNA within the nucleus of the cell and by making selected regions of chromosomes available for transcription and replication. Principal Investigator's are Dr. Dan Carter and Dr. Gerard Bunick of New Century Pharmaceuticals.

  9. Particle-Size Analysis

    SciTech Connect

    Gee, Glendon W. ); Or, Dani; J.H. Dane and G.C. Topp

    2002-11-01

    Book Chapter describing methods of particle-size analysis for soils. Includes a variety of classification schemes. Standard methods for size distributions using pipet and hydrometer techniques are described. New laser-light scattering and related techniques are discussed. Complete with updated references.

  10. Indoor particle dynamics.

    PubMed

    Nazaroff, W W

    2004-01-01

    Airborne particulate matter is a diverse pollutant class whose excessive presence in indoor air contributes to an array of adverse health and material-damage effects. Particles are classified according to their diameter into three size modes: ultrafine (0.1 microm), accumulation (0.1-2 microm), and coarse (= 2 microm). These modes have largely distinct sources and composition, and they exhibit different dynamic behaviors. The concept of mass conservation or material balance provides a foundation for quantitatively and mechanistically linking important outcome variables, such as concentrations and exposures, to the influencing input parameters. The factors governing indoor particle concentrations include direct emissions from indoor sources, ventilation supply from outdoor air, filtration, deposition onto indoor surfaces, and removal from indoor air by means of ventilation. In some circumstances, transport and transformation processes within indoor environments may also play an important role in influencing particle concentrations and consequences. Such processes include mixing, interzonal transport, resuspension, coagulation, and phase change. The paper gives a practical overview of issues related to particulate matter indoors, as well as valuable information for understanding filtration and how particles contribute to adverse health effects.

  11. Particles and Fields

    NASA Astrophysics Data System (ADS)

    Georgi, Howard; Wilczek, Frank; Tinyakov, Peter; Tytgat, Michel

    2013-03-01

    2011 marked the hundredth anniversary both of the famous Solvay conferences, and of the Geiger-Marsden experiment that launched the modern understanding of subatomic structure. I was asked to survey the status and prospects of particle physics for the anniversary Solvay conference, with appropriate perspective. This is my attempt.

  12. RESONATOR PARTICLE SEPARATOR

    DOEpatents

    Blewett, J.P.; Kiesling, J.D.

    1963-06-11

    A wave-guide resonator structure is designed for use in separating particles of equal momentum but differing in mass, having energies exceeding one billion eiectron volts. The particles referred to are those of sub-atomic size and are generally produced as a result of the bombardment of a target by a beam such as protons produced in a high energy accelerator. In the resonator a travelling electric wave is produced which travels at the same rate of speed as the unwanted particle which is thus deflected continuously over the length of the resonator. The wanted particle is slightly out of phase with the travelling wave so that over the whole length of the resonator it has a net deflection of substantially zero. The travelling wave is established in a wave guide of rectangular cross section in which stubs are provided to store magnetic wave energy leaving the electric wave energy in the main structure to obtain the desired travelling wave and deflection. The stubs are of such shape and spacing to establish a critical mathemitical relationship. (AEC)

  13. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  14. Universality of particle multiplicities

    NASA Astrophysics Data System (ADS)

    Goulianos, K.

    1994-09-01

    We discuss the scaling properties and universality aspects of the rapidity and multiplicity distributions of particles produced in high energy hadronic and e(+)e(-) interactions. This paper is based on material presented in three lectures on pomeron phenomenology, which included a review of traditional soft pomeron physics and selected topics on hard diffraction processes probing the structure function of the pomeron.

  15. Nucleosome Core Particle

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Nucleosome Core Particle grown on STS-81. The fundamental structural unit of chromatin and is the basis for organization within the genome by compaction of DNA within the nucleus of the cell and by making selected regions of chromosomes available for transcription and replication. Principal Investigator's are Dr. Dan Carter and Dr. Gerard Bunick of New Century Pharmaceuticals.

  16. Particle Acceleration in Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi

    2005-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., active galactic nuclei (AGNs), gamma ray burst (GRBs), and Galactic microquasar systems usually have power-law emission spectra. Fermi acceleration is the mechanism usually assumed for the acceleration of particles in astrophysical environments.

  17. Elementary Particles and Forces.

    ERIC Educational Resources Information Center

    Quigg, Chris

    1985-01-01

    Discusses subatomic particles (quarks, leptons, and others) revealed by higher accelerator energies. A connection between forces at this subatomic level has been established, and prospects are good for a description of forces that encompass binding atomic nuclei. Colors, fundamental interactions, screening, camouflage, electroweak symmetry, and…

  18. Elementary particle interactions

    SciTech Connect

    Bugg, W.M.; Condo, G.T.; Handler, T.; Hart, E.L.; Ward, B.F.L.; Close, F.E.; Christophorou, L.G.

    1990-10-01

    This report discusses freon bubble chamber experiments exposed to {mu}{sup +} and neutrinos, photon-proton interactions; shower counter simulations; SLD detectors at the Stanford Linear Collider, and the detectors at the Superconducting Super Collider; elementary particle interactions; physical properties of dielectric materials used in High Energy Physics detectors; and Nuclear Physics. (LSP)

  19. Contextuality of identical particles

    NASA Astrophysics Data System (ADS)

    Kurzyński, Paweł

    2017-01-01

    There exist quantum phenomena that cannot be explained by noncontextual hidden-variable theories, yet the majority of them requires measurements that are performed on a single quantum system at a time. This fact constrains the phenomenon of contextuality to the microscopic domain. It is therefore natural to ask if quantum contextuality can be observed in measurements on collections of particles. Since particles in nature are identical, one can expect that such contextuality would be linked to bosonic and fermionic properties. Analysis of quantum contextuality in such scenarios would broaden our understanding of nonclassical effects in composite systems and perhaps would give us a hint on how to observe quantum phenomena in the macroscopic world. In this work I propose a generalization of quantum contextuality to the case of many identical particles. I show that a type of contextuality exhibited by a collection of particles (state dependent, state independent, or noncontextual) depends on their type and their number. I also discuss further properties of this generalization and identify major open questions.

  20. Particle Astrophysics Using Balloons

    NASA Astrophysics Data System (ADS)

    Seo, E. S.

    Cosmic rays, energetic particles coming from outer space, bring us information about the physical processes that accelerate particles to relativistic energies, about the effects of those particles in driving dynamical processes in our Galaxy, and about the distribution of matter and fields in interstellar space. Cosmic rays were discovered in the early twentieth century using a balloon-borne electroscope. Balloons are currently being used for answering fundamental questions about the cosmos: (1) Is the Universe symmetric, and if so where is the antimatter? (2) What is the dark matter? (3) How do cosmic rays get their enormous energies? (4) Can the entire energy spectrum of cosmic rays result from a single acceleration mechanism? (5) Are supernovae really the sources of cosmic rays? (6) What is the history of cosmic rays in the Galaxy? (7) What is the origin of the "knee" in the cosmic ray energy spectrum? etc. The status of results from past balloon-borne measurements and expected results from ongoing and planned future balloon-borne particle astrophysics experiments will be reviewed.

  1. Battery Particle Simulation

    SciTech Connect

    2014-09-15

    Two simulations show the differences between a battery being drained at a slower rate, over a full hour, versus a faster rate, only six minutes (a tenth of an hour). In both cases battery particles go from being fully charged (green) to fully drained (red), but there are significant differences in the patterns of discharge based on the rate.

  2. Particle Swarm Optimization Toolbox

    NASA Technical Reports Server (NTRS)

    Grant, Michael J.

    2010-01-01

    The Particle Swarm Optimization Toolbox is a library of evolutionary optimization tools developed in the MATLAB environment. The algorithms contained in the library include a genetic algorithm (GA), a single-objective particle swarm optimizer (SOPSO), and a multi-objective particle swarm optimizer (MOPSO). Development focused on both the SOPSO and MOPSO. A GA was included mainly for comparison purposes, and the particle swarm optimizers appeared to perform better for a wide variety of optimization problems. All algorithms are capable of performing unconstrained and constrained optimization. The particle swarm optimizers are capable of performing single and multi-objective optimization. The SOPSO and MOPSO algorithms are based on swarming theory and bird-flocking patterns to search the trade space for the optimal solution or optimal trade in competing objectives. The MOPSO generates Pareto fronts for objectives that are in competition. A GA, based on Darwin evolutionary theory, is also included in the library. The GA consists of individuals that form a population in the design space. The population mates to form offspring at new locations in the design space. These offspring contain traits from both of the parents. The algorithm is based on this combination of traits from parents to hopefully provide an improved solution than either of the original parents. As the algorithm progresses, individuals that hold these optimal traits will emerge as the optimal solutions. Due to the generic design of all optimization algorithms, each algorithm interfaces with a user-supplied objective function. This function serves as a "black-box" to the optimizers in which the only purpose of this function is to evaluate solutions provided by the optimizers. Hence, the user-supplied function can be numerical simulations, analytical functions, etc., since the specific detail of this function is of no concern to the optimizer. These algorithms were originally developed to support entry

  3. Neutral particle lithography

    NASA Astrophysics Data System (ADS)

    Craver, Barry Paul

    Neutral particle lithography (NPL) is a high resolution, proximity exposure technique where a broad beam of energetic neutral particles floods a stencil mask and transmitted beamlets transfer the mask pattern to resist on a substrate, such that each feature is printed in parallel, rather than in the serial manner of electron beam lithography. It preserves the advantages of ion beam lithography (IBL), including extremely large depth-of-field, sub-5 nm resist scattering, and the near absence of diffraction, yet is intrinsically immune to charge-related artifacts including line-edge roughness and pattern placement errors due to charge accumulation on the mask and substrate. In our experiments, a neutral particle beam is formed by passing an ion beam (e.g., 30 keV He+) through a high pressure helium gas cell (e.g., 100 mTorr) to convert the ions to energetic neutrals through charge transfer scattering. The resolution of NPL is generally superior to that of IBL for applications involving insulating substrates, large proximity gaps, and ultra-small features. High accuracy stepped exposures with energetic neutral particles, where magnetic or electrostatic deflection is impossible, have been obtained by clamping the mask to the wafer, setting the proximity gap with a suitable spacer, and mechanically inclining the mask/wafer stack relative to the beam. This approach is remarkably insensitive to vibration and thermal drift; nanometer scale image offsets have been obtained with +/-2 nm placement accuracy for experiments lasting over one hour. Using this nanostepping technique, linewidth versus dose curves were obtained, from which the NPL lithographic blur was determined as 4.4+/-1.4 nm (1sigma), which is 2-3 times smaller than the blur of electron beam lithography. Neutral particle lithography has the potential to form high density, periodic patterns with sub-10 nm resolution.

  4. Movement of particles using sequentially activated dielectrophoretic particle trapping

    DOEpatents

    Miles, Robin R.

    2004-02-03

    Manipulation of DNA and cells/spores using dielectrophoretic (DEP) forces to perform sample preparation protocols for polymerized chain reaction (PCR) based assays for various applications. This is accomplished by movement of particles using sequentially activated dielectrophoretic particle trapping. DEP forces induce a dipole in particles, and these particles can be trapped in non-uniform fields. The particles can be trapped in the high field strength region of one set of electrodes. By switching off this field and switching on an adjacent electrodes, particles can be moved down a channel with little or no flow.

  5. Magnetic flocculation of paramagnetic particles

    SciTech Connect

    Tsouris, C.; Scott, T.C.

    1994-09-01

    An experimental apparatus has been assembled for the flocculation study of paramagnetic particles under the influence of a strong magnetic field. A magnetic field of strength up to 6 T is generated by a cryogenic magnet operating near liquid helium temperatures. Experimental information is obtained from fluctuation and intensity measurements of light passing through a particle suspension located in a uniform magnetic field. Particle flocculation is described by a Brownian flocculation model in which hydrodynamic, van der Waals, double-layer, and magnetic forces are incorporated for the estimation of the particle flocculation rate. A population-balance model is employed in conjunction with the flocculation model to predict the evolution of the particle size and composition or magnetic susceptibility with time. The effects of magnetic-field strength, magnetic susceptibility of the particles, particle size, and zeta potential are investigated. Results show that particle size and magnetic susceptibility each play an important role in the selective flocculation of particles of different properties.

  6. Particle analyzing method and apparatus

    NASA Technical Reports Server (NTRS)

    Sinha, M. P.; Griffin, C. E.; Norris, D. D.; Friedlander, S. K. (Inventor)

    1980-01-01

    The rapid chemical analysis of particles in aerosols can be accomplished using an apparatus which produces a controlled stream of individual particles from an environment, and another apparatus which vaporizes and ionizes the particles moving in free flight, for analysis by a mass spectrometer. The device for producing the stream of particles includes a capillary tube through which the air with suspended particles moves, a skimmer with a small opening spaced from an end of the capillary tube to receive particles passing through the tube, and a vacuum pump which removes air from between the tube and skimmer and creates an inflow of air and particles through the tube. The particles passing through the skimmer opening can be simultaneously vaporized and ionized while in free flight, by a laser beam of sufficient intensity that is directed across the path of the free flying particles.

  7. Experimental Particle Physics

    SciTech Connect

    Rosenfeld, Carl; Mishra, Sanjib R.; Petti, Roberto; Purohit, Milind V.

    2014-08-31

    The high energy physics group at the University of South Carolina, under the leadership of Profs. S.R. Mishra, R. Petti, M.V. Purohit, J.R. Wilson (co-PI's), and C. Rosenfeld (PI), engaged in studies in "Experimental Particle Physics." The group collaborated with similar groups at other universities and at national laboratories to conduct experimental studies of elementary particle properties. We utilized the particle accelerators at the Fermi National Accelerator Laboratory (Fermilab) in Illinois, the Stanford Linear Accelerator Center (SLAC) in California, and the European Center for Nuclear Research (CERN) in Switzerland. Mishra, Rosenfeld, and Petti worked predominantly on neutrino experiments. Experiments conducted in the last fifteen years that used cosmic rays and the core of the sun as a source of neutrinos showed conclusively that, contrary to the former conventional wisdom, the "flavor" of a neutrino is not immutable. A neutrino of flavor "e," "mu," or "tau," as determined from its provenance, may swap its identity with one of the other flavors -- in our jargon, they "oscillate." The oscillation phenomenon is extraordinarily difficult to study because neutrino interactions with our instruments are exceedingly rare -- they travel through the earth mostly unimpeded -- and because they must travel great distances before a substantial proportion have made the identity swap. Three of the experiments that we worked on, MINOS, NOvA, and LBNE utilize a beam of neutrinos from an accelerator at Fermilab to determine the parameters governing the oscillation. Two other experiments that we worked on, NOMAD and MIPP, provide measurements supportive of the oscillation experiments. Good measurements of the neutrino oscillation parameters may constitute a "low energy window" on related phenomena that are otherwise unobservable because they would occur only at energies way above the reach of conceivable accelerators. Purohit and Wilson participated in the BaBar experiment

  8. Particle measurement systems and methods

    DOEpatents

    Steele, Paul T [Livermore, CA

    2011-10-04

    A system according to one embodiment includes a light source for generating light fringes; a sampling mechanism for directing a particle through the light fringes; and at least one light detector for detecting light scattered by the particle as the particle passes through the light fringes. A method according to one embodiment includes generating light fringes using a light source; directing a particle through the light fringes; and detecting light scattered by the particle as the particle passes through the light fringes using at least one light detector.

  9. Effective particle magnetic moment of multi-core particles

    NASA Astrophysics Data System (ADS)

    Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian; Wetterskog, Erik; Svedlindh, Peter; Lak, Aidin; Ludwig, Frank; van IJzendoorn, Leo J.; Westphal, Fritz; Grüttner, Cordula; Gehrke, Nicole; Gustafsson, Stefan; Olsson, Eva; Johansson, Christer

    2015-04-01

    In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems - BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm - and one single-core particle system - SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm.

  10. Particle detector spatial resolution

    DOEpatents

    Perez-Mendez, Victor

    1992-01-01

    Method and apparatus for producing separated columns of scintillation layer material, for use in detection of X-rays and high energy charged particles with improved spatial resolution. A pattern of ridges or projections is formed on one surface of a substrate layer or in a thin polyimide layer, and the scintillation layer is grown at controlled temperature and growth rate on the ridge-containing material. The scintillation material preferentially forms cylinders or columns, separated by gaps conforming to the pattern of ridges, and these columns direct most of the light produced in the scintillation layer along individual columns for subsequent detection in a photodiode layer. The gaps may be filled with a light-absorbing material to further enhance the spatial resolution of the particle detector.

  11. Particle detector spatial resolution

    DOEpatents

    Perez-Mendez, V.

    1992-12-15

    Method and apparatus for producing separated columns of scintillation layer material, for use in detection of X-rays and high energy charged particles with improved spatial resolution is disclosed. A pattern of ridges or projections is formed on one surface of a substrate layer or in a thin polyimide layer, and the scintillation layer is grown at controlled temperature and growth rate on the ridge-containing material. The scintillation material preferentially forms cylinders or columns, separated by gaps conforming to the pattern of ridges, and these columns direct most of the light produced in the scintillation layer along individual columns for subsequent detection in a photodiode layer. The gaps may be filled with a light-absorbing material to further enhance the spatial resolution of the particle detector. 12 figs.

  12. Narrowband magnetic particle imaging.

    PubMed

    Goodwill, Patrick W; Scott, Greig C; Stang, Pascal P; Conolly, Steven M

    2009-08-01

    The magnetic particle imaging (MPI) method directly images the magnetization of super-paramagnetic iron oxide (SPIO) nanoparticles, which are contrast agents commonly used in magnetic resonance imaging (MRI). MPI, as originally envisioned, requires a high-bandwidth receiver coil and preamplifier, which are difficult to optimally noise match. This paper introduces Narrowband MPI, which dramatically reduces bandwidth requirements and increases the signal-to-noise ratio for a fixed specific absorption rate. We employ a two-tone excitation (called intermodulation) that can be tailored for a high-Q, narrowband receiver coil. We then demonstrate a new MPI instrument capable of full 3-D tomographic imaging of SPIO particles by imaging acrylic and tissue phantoms.

  13. Aviation Particle Emissions Workshop

    NASA Technical Reports Server (NTRS)

    Wey, Chowen C. (Editor)

    2004-01-01

    The Aviation Particle Emissions Workshop was held on November 18 19, 2003, in Cleveland, Ohio. It was sponsored by the National Aeronautic and Space Administration (NASA) under the Vehicle Systems Program (VSP) and the Ultra- Efficient Engine Technology (UEET) Project. The objectives were to build a sound foundation for a comprehensive particulate research roadmap and to provide a forum for discussion among U.S. stakeholders and researchers. Presentations included perspectives from the Federal Aviation Administration, the U.S. Environmental Protection Agency, NASA, and United States airports. There were five interactive technical sessions: sampling methodology, measurement methodology, particle modeling, database, inventory and test venue, and air quality. Each group presented technical issues which generated excellent discussion. The five session leads collaborated with their members to present summaries and conclusions to each content area.

  14. Cosmology and particle physics

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.

    1988-01-01

    The interplay between cosmology and elementary particle physics is discussed. The standard cosmology is reviewed, concentrating on primordial nucleosynthesis and discussing how the standard cosmology has been used to place constraints on the properties of various particles. Baryogenesis is discussed, showing how a scenario in which the B-, C-, and CP-violating interactions in GUTs provide a dynamical explanation for the predominance of matter over antimatter and for the present baryon-to-photon ratio. It is shown how the very early dynamical evolution of a very weakly coupled scalar field which is initially displaced from the minimum of its potential may explain a handful of very fundamental cosmological facts which are not explained by the standard cosmology.

  15. Cosmology and particle physics

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.

    1988-01-01

    The interplay between cosmology and elementary particle physics is discussed. The standard cosmology is reviewed, concentrating on primordial nucleosynthesis and discussing how the standard cosmology has been used to place constraints on the properties of various particles. Baryogenesis is discussed, showing how a scenario in which the B-, C-, and CP-violating interactions in GUTs provide a dynamical explanation for the predominance of matter over antimatter and for the present baryon-to-photon ratio. It is shown how the very early dynamical evolution of a very weakly coupled scalar field which is initially displaced from the minimum of its potential may explain a handful of very fundamental cosmological facts which are not explained by the standard cosmology.

  16. Multicolor particle shadow accelerometry

    NASA Astrophysics Data System (ADS)

    McPhail, M. J.; Krane, M. H.; Fontaine, A. A.; Goss, L.; Crafton, J.

    2015-04-01

    This paper describes the extension of multicolor particle shadow velocimetry (CPSV) to the measurement of local acceleration in an Eulerian frame of reference. A validation experiment was conducted on a pendulous disk undergoing unsteady rigid body rotation. Angular velocity and acceleration profiles by CPSA are presented along with a comparison to recordings by an accelerometer mounted on the pendulum. CPSA is also demonstrated in a fully-developed turbulent pipe flow. Profiles of standard deviation of the local acceleration in the near wall region ≤ft(0<~{{y}+}<75\\right) are compared to similar measurements by Christensen and Adrian. A favorable comparison is found between CPSA and particle image accelerometry (PIA). The effect of acceleration time delay, or the time between two velocity estimates, on local acceleration estimates is discussed.

  17. Research in particle physics

    SciTech Connect

    Not Available

    1993-08-01

    This proposal presents the research accomplishments and ongoing activities of Boston University researchers in high energy physics. Some changes have been made in the structure of the program from the previous arrangement of tasks. Task B, Accelerator Design Physics, is being submitted as a separate proposal for an independent grant; this will be consistent with the nature of the research and the source of funding. We are active in seven principal areas which will be discussed in this report: Colliding Beams - physics of e{sup +}e{sup {minus}} and {bar p}p collisions; MACRO Experiment - search for magnetic monopoles and study of cosmic rays; Proton Decay - search for nucleon instability and study of neutrino interactions; Particle Theory - theoretical high energy particle physics, including two Outstanding Junior Investigator awards; Muon G-2 - measurement of the anomalous magnetic moment of the muon; SSCintcal - calorimetry for the GEM Experiment; and Muon detectors for the GEM Experiment.

  18. Particle processing technology

    NASA Astrophysics Data System (ADS)

    Yoshio, Sakka

    2014-02-01

    In recent years, there has been strong demand for the development of novel devices and equipment that support advanced industries including IT/semiconductors, the environment, energy and aerospace along with the achievement of higher efficiency and reduced environmental impact. Many studies have been conducted on the fabrication of innovative inorganic materials with novel individual properties and/or multifunctional properties including electrical, dielectric, thermal, optical, chemical and mechanical properties through the development of particle processing. The fundamental technologies that are key to realizing such materials are (i) the synthesis of nanoparticles with uniform composition and controlled crystallite size, (ii) the arrangement/assembly and controlled dispersion of nanoparticles with controlled particle size, (iii) the precise structural control at all levels from micrometer to nanometer order and (iv) the nanostructural design based on theoretical/experimental studies of the correlation between the local structure and the functions of interest. In particular, it is now understood that the application of an external stimulus, such as magnetic energy, electrical energy and/or stress, to a reaction field is effective in realizing advanced particle processing [1-3]. This special issue comprises 12 papers including three review papers. Among them, seven papers are concerned with phosphor particles, such as silicon, metals, Si3N4-related nitrides, rare-earth oxides, garnet oxides, rare-earth sulfur oxides and rare-earth hydroxides. In these papers, the effects of particle size, morphology, dispersion, surface states, dopant concentration and other factors on the optical properties of phosphor particles and their applications are discussed. These nanoparticles are classified as zero-dimensional materials. Carbon nanotubes (CNT) and graphene are well-known one-dimensional (1D) and two-dimensional (2D) materials, respectively. This special issue also

  19. Particle-mesh techniques

    NASA Technical Reports Server (NTRS)

    Macneice, Peter

    1995-01-01

    This is an introduction to numerical Particle-Mesh techniques, which are commonly used to model plasmas, gravitational N-body systems, and both compressible and incompressible fluids. The theory behind this approach is presented, and its practical implementation, both for serial and parallel machines, is discussed. This document is based on a four-hour lecture course presented by the author at the NASA Summer School for High Performance Computational Physics, held at Goddard Space Flight Center.

  20. Universality of particle multiplicities

    SciTech Connect

    Goulianos, K. |

    1994-09-01

    We discuss the scaling properties and universality aspects of the rapidity and multiplicity distributions of particles produced in high energy hadronic and e{sup +}e{sup {minus}} interactions. This paper is based on material presented in three lectures on pomeron phenomenology, which included a review of traditional soft pomeron physics and selected topics on hard diffraction processes probing the structure function of the pomeron.

  1. Dynamic radioactive particle source

    DOEpatents

    Moore, Murray E; Gauss, Adam Benjamin; Justus, Alan Lawrence

    2012-06-26

    A method and apparatus for providing a timed, synchronized dynamic alpha or beta particle source for testing the response of continuous air monitors (CAMs) for airborne alpha or beta emitters is provided. The method includes providing a radioactive source; placing the radioactive source inside the detection volume of a CAM; and introducing an alpha or beta-emitting isotope while the CAM is in a normal functioning mode.

  2. Incremental Particle Swarm Optimization

    NASA Astrophysics Data System (ADS)

    Xu, Xiaohua; Pan, Zhoujin; Xi, Yanqiu; Chen, Ling

    By simulating the population size of the human evolution, a PSO algorithm with increment of particle size (IPPSO) was proposed. Without changing the PSO operations, IPPSO can obtain better solutions with less time cost by modifying the structure of traditional PSO. Experimental results show that IPPSO using logistic model is more efficient and requires less computation time than using linear function in solving more complex program problems.

  3. Radiation in Particle Simulations

    SciTech Connect

    More, R; Graziani, F; Glosli, J; Surh, M

    2010-11-19

    Hot dense radiative (HDR) plasmas common to Inertial Confinement Fusion (ICF) and stellar interiors have high temperature (a few hundred eV to tens of keV), high density (tens to hundreds of g/cc) and high pressure (hundreds of megabars to thousands of gigabars). Typically, such plasmas undergo collisional, radiative, atomic and possibly thermonuclear processes. In order to describe HDR plasmas, computational physicists in ICF and astrophysics use atomic-scale microphysical models implemented in various simulation codes. Experimental validation of the models used to describe HDR plasmas are difficult to perform. Direct Numerical Simulation (DNS) of the many-body interactions of plasmas is a promising approach to model validation but, previous work either relies on the collisionless approximation or ignores radiation. We present four methods that attempt a new numerical simulation technique to address a currently unsolved problem: the extension of molecular dynamics to collisional plasmas including emission and absorption of radiation. The first method applies the Lienard-Weichert solution of Maxwell's equations for a classical particle whose motion is assumed to be known. The second method expands the electromagnetic field in normal modes (planewaves in a box with periodic boundary-conditions) and solves the equation for wave amplitudes coupled to the particle motion. The third method is a hybrid molecular dynamics/Monte Carlo (MD/MC) method which calculates radiation emitted or absorbed by electron-ion pairs during close collisions. The fourth method is a generalization of the third method to include small clusters of particles emitting radiation during close encounters: one electron simultaneously hitting two ions, two electrons simultaneously hitting one ion, etc. This approach is inspired by the virial expansion method of equilibrium statistical mechanics. Using a combination of these methods we believe it is possible to do atomic-scale particle simulations of

  4. Interplanetary charged particle environments

    NASA Technical Reports Server (NTRS)

    Divine, T. N.

    1973-01-01

    Current state-of-the-art knowledge of the solar wind, solar particle events, and galactic cosmic rays is reviewed for the development of space vehicle design criteria based on these interplanetary environments. These criteria are described quantitatively in terms of intensity, flux and fluence, and their dependences on time, position and energy, and the associated probabilities and related parameters, for electrons, protons and other ions.

  5. Introduction: Particles and fields

    NASA Astrophysics Data System (ADS)

    Moore, Thomas; Spann, James

    2017-02-01

    A Conference on Measurement Techniques for Solar and Space Physics was held on 20-24 April 2015 in Boulder, Colorado, at the National Center for Atmospheric Research Center Green Campus. The present volume collects together the papers from this conference in the categories of particles and fields. This also includes neutral gas techniques as well as low-energy ionospheric plasmas and their interactions with spacecrafts.

  6. Relaxation from particle production

    NASA Astrophysics Data System (ADS)

    Hook, Anson; Marques-Tavares, Gustavo

    2016-12-01

    We consider using particle production as a friction force by which to implement a "Relaxion" solution to the electroweak hierarchy problem. Using this approach, we are able to avoid superplanckian field excursions and avoid any conflict with the strong CP problem. The relaxation mechanism can work before, during or after inflation allowing for inflationary dynamics to play an important role or to be completely decoupled.

  7. Relaxation from particle production

    SciTech Connect

    Hook, Anson; Marques-Tavares, Gustavo

    2016-12-20

    Here, we consider using particle production as a friction force by which to implement a “Relaxion” solution to the electroweak hierarchy problem. Using this approach, we are able to avoid superplanckian field excursions and avoid any conflict with the strong CP problem. The relaxation mechanism can work before, during or after inflation allowing for inflationary dynamics to play an important role or to be completely decoupled.

  8. PARTICLE BEAM TRACKING CIRCUIT

    DOEpatents

    Anderson, O.A.

    1959-05-01

    >A particle-beam tracking and correcting circuit is described. Beam induction electrodes are placed on either side of the beam, and potentials induced by the beam are compared in a voltage comparator or discriminator. This comparison produces an error signal which modifies the fm curve at the voltage applied to the drift tube, thereby returning the orbit to the preferred position. The arrangement serves also to synchronize accelerating frequency and magnetic field growth. (T.R.H.)

  9. Robust mobile robot localization: From single-robot uncertainties to multi-robot interdependencies

    NASA Astrophysics Data System (ADS)

    Roumeliotis, Stergios I.

    2000-10-01

    Robust localization is the problem of determining the position of a mobile robot with respect to a global or local frame of reference in the presence of sensor noise, uncertainties and potential failures. Previous work in this field has used Kalman filters to reduce the effects of sensor noise on updates of the vehicle position estimate or Bayesian multiple hypothesis to resolve the ambiguity associated with the identification of detected landmarks. This dissertation introduces a general framework for localization that subsumes both approaches in a single architecture and applies it to the general problem of localizing a mobile robot within a known environment. Odometric and/or inertial sensors are fused with data obtained from exteroceptive sensors. The approach is validated by solution of the "kidnapped robot" problem. The second problem treated in this dissertation concerns the common assumption that all sensors provide information at the same rate. This assumption is relaxed by allowing high rate noisy odometric or inertial data from kinetic sensors while absolute attitude and/or position data (e.g., from sun sensors) are obtained infrequently. We address the resulting observability limitation by incorporating a Smoother in the attitude estimation algorithm. Smoothing of the attitude estimates reduces the overall uncertainty and allows for longer traverses before a new absolute orientation measurement is required. Simulation examples also show the ability of this method to increase the accuracy of robot mapping. The third problem concerns multiple robots collaborating on a single task. In prior research with a group of, say M, robots the group localization problem is usually approached by independently solving M pose estimation problems. When collaboration among robots exists, current methods usually require that at least one member of the group holds a fixed position while visual contact with all the other members of the team is maintained. If these two conditions are not met, uncorrelated pose estimates can lead to overly optimistic estimates. We introduce a new distributed Kalman filtering approach for collective localization that overcomes the previous limitations and combines optimally all available positioning information amongst the group members.

  10. Robust Behavior-Based Control for Distributed Multi-Robot Collection Tasks

    DTIC Science & Technology

    2000-01-01

    Press: New York. [18] Henrik Hautop Lund and Luigi Pagliarini, \\Robocup jr. with lego mindstorms," in Proceedings of the 2000 IEEE Interna- tional...Conference on Robotics and Automation, San Francisco, CA, April 2000, IEEE. [19] Mattias Lindstrom, Anders Oreback, and Henrik I. Christensen, \\Berra: A...ior Fusion using Voting, Ph.D. thesis, Institute of Electronic Systems, Alborg University, Denmark, 1998. [23] Paolo Pirjanian, Henrik I. Christensen

  11. Distributed control of multi-robot teams: Cooperative baton passing task

    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. 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, they describe the implementation of this architecture on a team of physical mobile robots performing a cooperative baton passing task. These experiments illustrate the ability of ALLIANCE to achieve adaptive, fault-tolerant cooperative control amidst dynamic changes during the task.

  12. Formation control of multi-robots for on-orbit assembly of large solar sails

    NASA Astrophysics Data System (ADS)

    Hu, Quan; Zhang, Yao; Zhang, Jingrui; Hu, Haiyan

    2016-06-01

    This study focuses on the formation control of four robots used for the on-orbit construction of a large solar sail. The solar sail under consideration is non-spinning and has a 1 km2 area. It includes a hub as the central body and four large booms supporting the lightweight films. Four formation operating space robots capable of walking on the boom structure are utilized to deploy the sail films. Because of the large size and mass of the sail, the robots should remain in formation during the sail deployment to avoid dramatic changes in the system properties. In this paper, the formation control issue of the four robots is solved by an adaptive sliding mode controller. A disturbance observer with finite-time convergence is embedded to improve the control performance. The proposed controller is capable of resisting the strong uncertainties in the operation and do not require the accurate parameters of the system. The stability is proven, and numerical simulations are provided to validate the effectiveness of the control strategy.

  13. Human-Agent Teaming for Multi-Robot Control: A Literature Review

    DTIC Science & Technology

    2013-02-01

    enhance their SA of their tasking environments (for a review on human factors issues related to information visualization, see Robertson et al., 2009...Journal of Personality and Social Psychology 1985, 49, 95–112. Robertson , G.; Czerwinski, M.; Fisher, D.; Lee, B. Selected Human Factors Issues in...Portugal, 12–16 May 2008. 44 Schumacher, E.; Seymour , T.; Glass, J.; Fencsik, D.; Lauber, E.; Kieras, D. et al. Virtually Perfect Time Sharing in

  14. A Behavior-Based Strategy for Single and Multi-Robot Autonomous Exploration

    PubMed Central

    Cepeda, Jesus S.; Chaimowicz, Luiz; Soto, Rogelio; Gordillo, José L.; Alanís-Reyes, Edén A.; Carrillo-Arce, Luis C.

    2012-01-01

    In this paper, we consider the problem of autonomous exploration of unknown environments with single and multiple robots. This is a challenging task, with several potential applications. We propose a simple yet effective approach that combines a behavior-based navigation with an efficient data structure to store previously visited regions. This allows robots to safely navigate, disperse and efficiently explore the environment. A series of experiments performed using a realistic robotic simulator and a real testbed scenario demonstrate that our technique effectively distributes the robots over the environment and allows them to quickly accomplish their mission in large open spaces, narrow cluttered environments, dead-end corridors, as well as rooms with minimum exits.

  15. Heterogeneous Multi-Robot Multi-Sensor Platform for Intruder Detection

    DTIC Science & Technology

    2009-09-15

    ECE Dept. at Stevens for both 802.11 ( WiFi ) networks as well as 802.15.4 (ZigBee) networks to localize the mobile sensor nodes; (2) we investigated...developed and deployed a prototype of the localization system in the ECE Dept. at Stevens for both 802.11 ( WiFi ) networks as well as 802.15.4 (ZigBee...developed and deployed a prototype of the localization system in the ECE Dept. at Stevens for both 802.11 ( WiFi ) networks as well as 802.15.4 (ZigBee

  16. Market-Based Coordination and Auditing Mechanisms for Self-Interested Multi-Robot Systems

    ERIC Educational Resources Information Center

    Ham, MyungJoo

    2009-01-01

    We propose market-based coordinated task allocation mechanisms, which allocate complex tasks that require synchronized and collaborated services of multiple robot agents to robot agents, and an auditing mechanism, which ensures proper behaviors of robot agents by verifying inter-agent activities, for self-interested, fully-distributed, and…

  17. Autonomous Multi-Robot Search for a Hazardous Source in a Turbulent Environment

    PubMed Central

    Ristic, Branko; Angley, Daniel; Moran, Bill; Palmer, Jennifer L.

    2017-01-01

    Finding the source of an accidental or deliberate release of a toxic substance into the atmosphere is of great importance for national security. The paper presents a search algorithm for turbulent environments which falls into the class of cognitive (infotaxi) algorithms. Bayesian estimation of the source parameter vector is carried out using the Rao–Blackwell dimension-reduction method, while the robots are controlled autonomously to move in a scalable formation. Estimation and control are carried out in a centralised replicated fusion architecture assuming all-to-all communication. The paper presents a comprehensive numerical analysis of the proposed algorithm, including the search-time and displacement statistics. PMID:28430120

  18. Distributed multi-robot sensing and tracking: a behavior-based approach

    SciTech Connect

    Parker, L.E.

    1995-12-31

    An important issue that arises in the automation of many large-scale surveillance and reconnaissance tasks is that of tracking the movements of (or maintaining passive contact with) objects navigating in a bounded area of interest. Oftentimes in these problems, the area to be monitored will move over time or will not permit fixed sensors, thus requiring a team of mobile sensors -- or robots -- to monitor the area collectively. In these situations, the robots must not only have mechanisms for determining how to track objects and how to fuse information from neighboring robots, but they must also have distributed control strategies for ensuring that the entire area of interest is continually covered to the greatest extent possible. This paper focuses on the distributed control issue by describing a proposed decentralized control mechanism that allows a team of robots to collectively track and monitor objects in an uncluttered area of interest. The approach is based upon an extension to the ALLIANCE behavior-based architecture that generalizes from the domain of loosely-coupled, independent applications to the domain of strongly cooperative applications, in which the action selection of a robot is dependent upon the actions selected by its teammates. We conclude the paper by describing our ongoing implementation of the proposed approach on a team of four mobile robots.

  19. Real-Time Motion Planning and Safe Navigation in Dynamic Multi-Robot Environments

    DTIC Science & Technology

    2006-12-15

    ground truth from which to measure true error, the error can be estimated by smoothing the data with a large Gaussian kernel (σ = 10) and then comparing...Uncorrelated readings would show up as a circular 2D Gaussian cloud. Note the structure in the plot for a single patch, and the unstructured but...kinematic and dynamic limitations on the agent which may have to be considered for solving navigation problems. Other remaining differential processes on the

  20. Experiments Toward the Application of Multi-Robot Systems to Disaster-Relief Scenarios

    DTIC Science & Technology

    2015-09-01

    responsibility is assessment, such as dislocated populations, degree of property damage, and remaining communications infrastructure. These are all...PointCioud Sensor Data - ~ Channel I Grid Produ<t I ~ Point Cloud 1- Renderer l ’I Grid Renderer ~ OmniCache Fig . 3 The OmniMapper