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Sample records for multiple maneuvering targets

  1. Multiple Maneuvering Target Tracking by Improved Particle Filter Based on Multiscan JPDA

    Jing Liu

    2012-01-01

    Full Text Available The multiple maneuvering target tracking algorithm based on a particle filter is addressed. The equivalent-noise approach is adopted, which uses a simple dynamic model consisting of target state and equivalent noise which accounts for the combined effects of the process noise and maneuvers. The equivalent-noise approach converts the problem of maneuvering target tracking to that of state estimation in the presence of nonstationary process noise with unknown statistics. A novel method for identifying the nonstationary process noise is proposed in the particle filter framework. Furthermore, a particle filter based multiscan Joint Probability Data Association (JPDA filter is proposed to deal with the data association problem in a multiple maneuvering target tracking. In the proposed multiscan JPDA algorithm, the distributions of interest are the marginal filtering distributions for each of the targets, and these distributions are approximated with particles. The multiscan JPDA algorithm examines the joint association events in a multiscan sliding window and calculates the marginal posterior probability based on the multiscan joint association events. The proposed algorithm is illustrated via an example involving the tracking of two highly maneuvering, at times closely spaced and crossed, targets, based on resolved measurements.

  2. A low-complexity interacting multiple model filter for maneuvering target tracking

    Khalid, Syed Safwan

    2017-01-22

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  3. A low-complexity interacting multiple model filter for maneuvering target tracking

    Khalid, Syed Safwan; Abrar, Shafayat

    2017-01-01

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  4. Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking.

    Liu, Hua; Wu, Wen

    2017-06-13

    For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF).

  5. Interacting Multiple Model (IMM Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking

    Hua Liu

    2017-06-01

    Full Text Available For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF. The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF, the interacting multiple model cubature Kalman filter (IMMCKF and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF.

  6. Trajectory Control of Rendezvous with Maneuver Target Spacecraft

    Zhou, Zhinqiang

    2012-01-01

    In this paper, a nonlinear trajectory control algorithm of rendezvous with maneuvering target spacecraft is presented. The disturbance forces on the chaser and target spacecraft and the thrust forces on the chaser spacecraft are considered in the analysis. The control algorithm developed in this paper uses the relative distance and relative velocity between the target and chaser spacecraft as the inputs. A general formula of reference relative trajectory of the chaser spacecraft to the target spacecraft is developed and applied to four different proximity maneuvers, which are in-track circling, cross-track circling, in-track spiral rendezvous and cross-track spiral rendezvous. The closed-loop differential equations of the proximity relative motion with the control algorithm are derived. It is proven in the paper that the tracking errors between the commanded relative trajectory and the actual relative trajectory are bounded within a constant region determined by the control gains. The prediction of the tracking errors is obtained. Design examples are provided to show the implementation of the control algorithm. The simulation results show that the actual relative trajectory tracks the commanded relative trajectory tightly. The predicted tracking errors match those calculated in the simulation results. The control algorithm developed in this paper can also be applied to interception of maneuver target spacecraft and relative trajectory control of spacecraft formation flying.

  7. Novel Fractional Order Calculus Extended PN for Maneuvering Targets

    Jikun Ye

    2017-01-01

    Full Text Available Based on the theory of fractional order calculus (FOC, a novel extended proportional guidance (EPN law for intercepting the maneuvering target is proposed. In the first part, considering the memory function and filter characteristic of FOC, the novel extended PN guidance algorithm is developed based on the conventional PN after introducing the properties and operation rules of FOC. Further, with the help of FOC theory, the average load and ballistics characteristics of proposed guidance law are analyzed. Then, using the small offset kinematic model, the robustness of the new guidance law against autopilot parameters is studied theoretically by analyzing the sensitivity of the closed loop guidance system. At last, representative numerical results show that the designed guidance law obtains a better performance than the traditional PN for maneuvering target.

  8. Differential Evolution Optimization for Targeting Spacecraft Maneuver Plans

    Mattern, Daniel

    2016-01-01

    Previous analysis identified specific orbital parameters as being safer for conjunction avoidance for the TDRS fleet. With TDRS-9 being considered an at-risk spacecraft, a potential conjunction concern was raised should TDRS-9 fail while at a longitude of 12W. This document summarizes the analysis performed to identify if these specific orbital parameters could be targeted using the remaining drift-termination maneuvers for the relocation of TDRS-9 from 41W longitude to 12W longitude.

  9. Analysis of LFM-waveform Libraries for Cognitive Tracking Maneuvering Targets

    Wang Hongyan

    2016-01-01

    Full Text Available Based on the idea of the waveform agility in cognitive radars,the waveform libraries for maneuvering target tracking are discussed. LFM-waveform libraries are designed according to different combinations of chirp parameters and FrFT rotation angles. By applying the interact multiple model (IMM algorithm in tracking maneuvering targets, transmitted waveform is called real time from the LFM-waveform libraries. The waveforms are selected from the library according to the criterion of maximum mutual information between the current state of knowledge of the model and the measurement. Simulation results show that waveform library containing certain amount LFM-waveforms can improve the performance of cognitive tracking radar.

  10. Integrated detection, estimation, and guidance in pursuit of a maneuvering target

    Dionne, Dany

    The thesis focuses on efficient solutions of non-cooperative pursuit-evasion games with imperfect information on the state of the system. This problem is important in the context of interception of future maneuverable ballistic missiles. However, the theoretical developments are expected to find application to a broad class of hybrid control and estimation problems in industry. The validity of the results is nevertheless confirmed using a benchmark problem in the area of terminal guidance. A specific interception scenario between an incoming target with no information and a single interceptor missile with noisy measurements is analyzed in the form of a linear hybrid system subject to additive abrupt changes. The general research is aimed to achieve improved homing accuracy by integrating ideas from detection theory, state estimation theory and guidance. The results achieved can be summarized as follows. (i) Two novel maneuver detectors are developed to diagnose abrupt changes in a class of hybrid systems (detection and isolation of evasive maneuvers): a new implementation of the GLR detector and the novel adaptive- H0 GLR detector. (ii) Two novel state estimators for target tracking are derived using the novel maneuver detectors. The state estimators employ parameterized family of functions to described possible evasive maneuvers. (iii) A novel adaptive Bayesian multiple model predictor of the ballistic miss is developed which employs semi-Markov models and ideas from detection theory. (iv) A novel integrated estimation and guidance scheme that significantly improves the homing accuracy is also presented. The integrated scheme employs banks of estimators and guidance laws, a maneuver detector, and an on-line governor; the scheme is adaptive with respect to the uncertainty affecting the probability density function of the filtered state. (v) A novel discretization technique for the family of continuous-time, game theoretic, bang-bang guidance laws is introduced. The

  11. Adaptive ISAR Imaging of Maneuvering Targets Based on a Modified Fourier Transform.

    Wang, Binbin; Xu, Shiyou; Wu, Wenzhen; Hu, Pengjiang; Chen, Zengping

    2018-04-27

    Focusing on the inverse synthetic aperture radar (ISAR) imaging of maneuvering targets, this paper presents a new imaging method which works well when the target's maneuvering is not too severe. After translational motion compensation, we describe the equivalent rotation of maneuvering targets by two variables-the relative chirp rate of the linear frequency modulated (LFM) signal and the Doppler focus shift. The first variable indicates the target's motion status, and the second one represents the possible residual error of the translational motion compensation. With them, a modified Fourier transform matrix is constructed and then used for cross-range compression. Consequently, the imaging of maneuvering is converted into a two-dimensional parameter optimization problem in which a stable and clear ISAR image is guaranteed. A gradient descent optimization scheme is employed to obtain the accurate relative chirp rate and Doppler focus shift. Moreover, we designed an efficient and robust initialization process for the gradient descent method, thus, the well-focused ISAR images of maneuvering targets can be achieved adaptively. Human intervention is not needed, and it is quite convenient for practical ISAR imaging systems. Compared to precedent imaging methods, the new method achieves better imaging quality under reasonable computational cost. Simulation results are provided to validate the effectiveness and advantages of the proposed method.

  12. A Cubature-Principle-Assisted IMM-Adaptive UKF Algorithm for Maneuvering Target Tracking Caused by Sensor Faults

    Huan Zhou

    2017-09-01

    Full Text Available Aimed at solving the problem of decreased filtering precision while maneuvering target tracking caused by non-Gaussian distribution and sensor faults, we developed an efficient interacting multiple model-unscented Kalman filter (IMM-UKF algorithm. By dividing the IMM-UKF into two links, the algorithm introduces the cubature principle to approximate the probability density of the random variable, after the interaction, by considering the external link of IMM-UKF, which constitutes the cubature-principle-assisted IMM method (CPIMM for solving the non-Gaussian problem, and leads to an adaptive matrix to balance the contribution of the state. The algorithm provides filtering solutions by considering the internal link of IMM-UKF, which is called a new adaptive UKF algorithm (NAUKF to address sensor faults. The proposed CPIMM-NAUKF is evaluated in a numerical simulation and two practical experiments including one navigation experiment and one maneuvering target tracking experiment. The simulation and experiment results show that the proposed CPIMM-NAUKF has greater filtering precision and faster convergence than the existing IMM-UKF. The proposed algorithm achieves a very good tracking performance, and will be effective and applicable in the field of maneuvering target tracking.

  13. Maneuver Analysis and Targeting Strategy for the Stardust Re-Entry Capsule

    Helfrich, Cliff; Bhat, Ramachand S.; Kangas, Julie A.; Wilson, Roby S.; Wong, Mau C.; Potts, Christopher L.; Williams, Kenneth E.

    2006-01-01

    The Stardust Sample Return Capsule (SRC) returned to Earth on January 15, 2006 after seven years of collecting interstellar and comet particles over three heliocentric revolutions, as shown in Figure 1. The SRC was carried on board the Stardust spacecraft, as shown in Figure 2. Because the spacecraft was built with unbalanced thrusters, turns and attitude control maintenance resulted in undesirable delta-v being imparted to the trajectory. As a result, a carefully planned maneuver strategy was devised to accurately target the Stardust capsule to the Utah Test and Training Range (UTTR). This paper provides an overview of the Stardust spacecraft and mission and describes the maneuver strategy that was employed to achieve the stringent targeting requirements for landing in Utah. In addition, an overview of Stardust maneuver analysis tools and techniques will also be presented.

  14. Tracking Maneuvering Group Target with Extension Predicted and Best Model Augmentation Method Adapted

    Linhai Gan

    2017-01-01

    Full Text Available The random matrix (RM method is widely applied for group target tracking. The assumption that the group extension keeps invariant in conventional RM method is not yet valid, as the orientation of the group varies rapidly while it is maneuvering; thus, a new approach with group extension predicted is derived here. To match the group maneuvering, a best model augmentation (BMA method is introduced. The existing BMA method uses a fixed basic model set, which may lead to a poor performance when it could not ensure basic coverage of true motion modes. Here, a maneuvering group target tracking algorithm is proposed, where the group extension prediction and the BMA adaption are exploited. The performance of the proposed algorithm will be illustrated by simulation.

  15. A Novel Guidance Law with Line-of-Sight Acceleration Feedback for Missiles against Maneuvering Targets

    Kemao Ma

    2014-01-01

    Full Text Available Terminal guidance law design and its implementation are considered for homing missiles against maneuvering targets. The lateral acceleration dynamics are taken into account in the design. In the guidance law design, the line-of-sight acceleration signals are incorporated into the acceleration reference signals to compensate for the targets’ maneuvers. Then the commanded accelerations are designed and the convergent tracking of the lateral accelerations to these signals is proven theoretically. In the guidance implementation, a linear high-gain differentiator is used to estimate the line-of-sight rates and the line-of-sight acceleration signals. To avoid the magnifying effects of higher order differentiation, a practical design of commanded accelerations is given to realize approximate tracking of the lateral accelerations to the given reference signals. Simulation is conducted for both cases with and without measurement noises. The simulation results justify the feasibility of the design and the implementation.

  16. A Novel Loss Recovery and Tracking Scheme for Maneuvering Target in Hybrid WSNs.

    Qian, Hanwang; Fu, Pengcheng; Li, Baoqing; Liu, Jianpo; Yuan, Xiaobing

    2018-01-25

    Tracking a mobile target, which aims to timely monitor the invasion of specific target, is one of the most prominent applications in wireless sensor networks (WSNs). Traditional tracking methods in WSNs only based on static sensor nodes (SNs) have several critical problems. For example, to void the loss of mobile target, many SNs must be active to track the target in all possible directions, resulting in excessive energy consumption. Additionally, when entering coverage holes in the monitoring area, the mobile target may be missing and then its state is unknown during this period. To tackle these problems, in this paper, a few mobile sensor nodes (MNs) are introduced to cooperate with SNs to form a hybrid WSN due to their stronger abilities and less constrained energy. Then, we propose a valid target tracking scheme for hybrid WSNs to dynamically schedule the MNs and SNs. Moreover, a novel loss recovery mechanism is proposed to find the lost target and recover the tracking with fewer SNs awakened. Furthermore, to improve the robustness and accuracy of the recovery mechanism, an adaptive unscented Kalman filter (AUKF) algorithm is raised to dynamically adjust the process noise covariance. Simulation results demonstrate that our tracking scheme for maneuvering target in hybrid WSNs can not only track the target effectively even if the target is lost but also maintain an excellent accuracy and robustness with fewer activated nodes.

  17. ISAR Imaging of Maneuvering Targets Based on the Modified Discrete Polynomial-Phase Transform

    Yong Wang

    2015-09-01

    Full Text Available Inverse synthetic aperture radar (ISAR imaging of a maneuvering target is a challenging task in the field of radar signal processing. The azimuth echo can be characterized as a multi-component polynomial phase signal (PPS after the translational compensation, and the high quality ISAR images can be obtained by the parameters estimation of it combined with the Range-Instantaneous-Doppler (RID technique. In this paper, a novel parameters estimation algorithm of the multi-component PPS with order three (cubic phase signal-CPS based on the modified discrete polynomial-phase transform (MDPT is proposed, and the corresponding new ISAR imaging algorithm is presented consequently. This algorithm is efficient and accurate to generate a focused ISAR image, and the results of real data demonstrate the effectiveness of it.

  18. Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver.

    Lima, Tainah P; Farinatti, Paulo T V; Rubini, Ercole C; Silva, Elirez B; Monteiro, Walace D

    2015-05-01

    This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises.

  19. Intercept Algorithm for Maneuvering Targets Based on Differential Geometry and Lyapunov Theory

    Yunes Sh. ALQUDSI

    2018-03-01

    Full Text Available Nowadays, the homing guidance is utilized in the existed and under development air defense systems (ADS to effectively intercept the targets. The targets became smarter and capable to fly and maneuver professionally and the tendency to design missile with a small warhead became greater, then there is a pressure to produce a more precise and accurate missile guidance system based on intelligent algorithms to ensure effective interception of highly maneuverable targets. The aim of this paper is to present an intelligent guidance algorithm that effectively and precisely intercept the maneuverable and smart targets by virtue of the differential geometry (DG concepts. The intercept geometry and engagement kinematics, in addition to the direct intercept condition are developed and expressed in DG terms. The guidance algorithm is then developed by virtue of DG and Lyapunov theory. The study terminates with 2D engagement simulation with illustrative examples, to demonstrate that, the derived DG guidance algorithm is a generalized guidance approach and the well-known proportional navigation (PN guidance law is a subset of this approach.

  20. A Fast Algorithm of Generalized Radon-Fourier Transform for Weak Maneuvering Target Detection

    Weijie Xia

    2016-01-01

    Full Text Available The generalized Radon-Fourier transform (GRFT has been proposed to detect radar weak maneuvering targets by realizing coherent integration via jointly searching in motion parameter space. Two main drawbacks of GRFT are the heavy computational burden and the blind speed side lobes (BSSL which will cause serious false alarms. The BSSL learning-based particle swarm optimization (BPSO has been proposed before to reduce the computational burden of GRFT and solve the BSSL problem simultaneously. However, the BPSO suffers from an apparent loss in detection performance compared with GRFT. In this paper, a fast implementation algorithm of GRFT using the BSSL learning-based modified wind-driven optimization (BMWDO is proposed. In the BMWDO, the BSSL learning procedure is also used to deal with the BSSL phenomenon. Besides, the MWDO adjusts the coefficients in WDO with Levy distribution and uniform distribution, and it outperforms PSO in a noisy environment. Compared with BPSO, the proposed method can achieve better detection performance with a similar computational cost. Several numerical experiments are also provided to demonstrate the effectiveness of the proposed method.

  1. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv's Distribution for Quadratic Frequency Modulation Signals.

    Jing, Fulong; Jiao, Shuhong; Hou, Changbo; Si, Weijian; Wang, Yu

    2017-06-21

    For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM) signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR) and the quadratic chirp rate (QCR) are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF) and modified scaled Fourier transform (mSFT), an effective parameter estimation algorithm is proposed-referred to as the Two-Dimensional product modified Lv's distribution (2D-PMLVD)-for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT) and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  2. Modified unscented Kalman filter using modified filter gain and variance scale factor for highly maneuvering target tracking

    Changyun Liu; Penglang Shui; Gang Wei; Song Li

    2014-01-01

    To improve the low tracking precision caused by lagged filter gain or imprecise state noise when the target highly maneu-vers, a modified unscented Kalman filter algorithm based on the improved filter gain and adaptive scale factor of state noise is pre-sented. In every filter process, the estimated scale factor is used to update the state noise covariance Qk, and the improved filter gain is obtained in the filter process of unscented Kalman filter (UKF) via predicted variance Pk|k-1, which is similar to the standard Kalman filter. Simulation results show that the proposed algorithm provides better accuracy and ability to adapt to the highly maneu-vering target compared with the standard UKF.

  3. Targeted therapy of multiple myeloma.

    Dolloff, Nathan G; Talamo, Giampaolo

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

  4. Development and experimentation of LQR/APF guidance and control for autonomous proximity maneuvers of multiple spacecraft

    Bevilacqua, R.; Lehmann, T.; Romano, M.

    2011-04-01

    This work introduces a novel control algorithm for close proximity multiple spacecraft autonomous maneuvers, based on hybrid linear quadratic regulator/artificial potential function (LQR/APF), for applications including autonomous docking, on-orbit assembly and spacecraft servicing. Both theoretical developments and experimental validation of the proposed approach are presented. Fuel consumption is sub-optimized in real-time through re-computation of the LQR at each sample time, while performing collision avoidance through the APF and a high level decisional logic. The underlying LQR/APF controller is integrated with a customized wall-following technique and a decisional logic, overcoming problems such as local minima. The algorithm is experimentally tested on a four spacecraft simulators test bed at the Spacecraft Robotics Laboratory of the Naval Postgraduate School. The metrics to evaluate the control algorithm are: autonomy of the system in making decisions, successful completion of the maneuver, required time, and propellant consumption.

  5. Multiple Target Laser Designator (MTLD)

    2007-03-01

    Optimized Liquid Crystal Scanning Element Optimize the Nonimaging Predictive Algorithm for Target Ranging, Tracking, and Position Estimation...commercial potential. 3.0 PROGRESS THIS QUARTER 3.1 Optimization of Nonimaging Holographic Antenna for Target Tracking and Position Estimation (Task 6) In

  6. Group Targets Tracking Using Multiple Models GGIW-CPHD Based on Best-Fitting Gaussian Approximation and Strong Tracking Filter

    Yun Wang

    2016-01-01

    Full Text Available Gamma Gaussian inverse Wishart cardinalized probability hypothesis density (GGIW-CPHD algorithm was always used to track group targets in the presence of cluttered measurements and missing detections. A multiple models GGIW-CPHD algorithm based on best-fitting Gaussian approximation method (BFG and strong tracking filter (STF is proposed aiming at the defect that the tracking error of GGIW-CPHD algorithm will increase when the group targets are maneuvering. The best-fitting Gaussian approximation method is proposed to implement the fusion of multiple models using the strong tracking filter to correct the predicted covariance matrix of the GGIW component. The corresponding likelihood functions are deduced to update the probability of multiple tracking models. From the simulation results we can see that the proposed tracking algorithm MM-GGIW-CPHD can effectively deal with the combination/spawning of groups and the tracking error of group targets in the maneuvering stage is decreased.

  7. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv’s Distribution for Quadratic Frequency Modulation Signals

    Fulong Jing

    2017-06-01

    Full Text Available For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR and the quadratic chirp rate (QCR are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF and modified scaled Fourier transform (mSFT, an effective parameter estimation algorithm is proposed—referred to as the Two-Dimensional product modified Lv’s distribution (2D-PMLVD—for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  8. Protein search for multiple targets on DNA

    Lange, Martin [Johannes Gutenberg University, Mainz 55122 (Germany); Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Kochugaeva, Maria [Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Kolomeisky, Anatoly B., E-mail: tolya@rice.edu [Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005 (United States)

    2015-09-14

    Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations.

  9. Cooperative target convergence using multiple agents

    Kwok, K.S.; Driessen, B.J.

    1997-01-01

    This work considers the problem of causing multiple (100''s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots

  10. Cooperative target convergence using multiple agents

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

  11. Targeting the Pim kinases in multiple myeloma.

    Keane, N A

    2015-07-17

    Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine\\/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and\\/or with novel drugs targeting other survival pathways in MM.

  12. A triple axes multiple target holder assembly

    Tribedi, L.C.; Narvekar, S.D.; Pillay, R.G.; Tandon, P.N.

    1993-01-01

    We have designed and fabricated a rotatable target holder assembly capable of accommodating 27 targets. The target foils are mounted along two concentric circles on a ss wheel. On the outer circle 18 targets can be mounted each 20deg apart, and on the inner circle the remaining targets are positioned each 40deg apart. The self supporting or carbon backed targets are mounted on thin frames and are placed concentrically at the targets are mounted on thin frames and are placed concentrically at the target position on the wheel. Three degrees of freedom are provided to the target holder assembly. (author). 1 fig

  13. Quantum partial search for uneven distribution of multiple target items

    Zhang, Kun; Korepin, Vladimir

    2018-06-01

    Quantum partial search algorithm is an approximate search. It aims to find a target block (which has the target items). It runs a little faster than full Grover search. In this paper, we consider quantum partial search algorithm for multiple target items unevenly distributed in a database (target blocks have different number of target items). The algorithm we describe can locate one of the target blocks. Efficiency of the algorithm is measured by number of queries to the oracle. We optimize the algorithm in order to improve efficiency. By perturbation method, we find that the algorithm runs the fastest when target items are evenly distributed in database.

  14. Effects of multiple scattering and target structure on photon emission

    Blankenbecler, R.

    1996-05-01

    The Landau-Pomeranchuk-Migdal effect is the suppression of Bethe-Heitler radiation caused by multiple scattering in the target medium. The quantum treatment given by S.D. Drell and the author for homogeneous targets of finite thickness will be reviewed. It will then be extended to structured targets. In brief, it is shown that radiators composed of separated plates or of a medium with a spatially varying radiation length can exhibit unexpected structure, even coherence maxima and minima, in their photon spectra. Finally, a functional integral method for performing the averaging implicit in multiple scattering will be briefly discussed and the leading corrections to previous results evaluated

  15. Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

    Xiaowen Zhang

    2018-02-01

    Full Text Available In this paper, the problem of cognitive radar (CR waveform optimization design for target detection and estimation in multiple extended targets situations is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended targets with unknown target impulse response (TIR. To address this problem, an improved algorithm is employed for target detection by maximizing the detection probability of the received echo on the promise of ensuring the TIR estimation precision. In this algorithm, an additional weight vector is introduced to achieve a trade-off among different targets. Both the estimate of TIR and transmit waveform can be updated at each step based on the previous step. Under the same constraint on waveform energy and bandwidth, the information theoretical approach is also considered. In addition, the relationship between the waveforms that are designed based on the two criteria is discussed. Unlike most existing works that only consider single target with temporally correlated characteristics, waveform design for multiple extended targets is considered in this method. Simulation results demonstrate that compared with linear frequency modulated (LFM signal, waveforms designed based on maximum detection probability and maximum mutual information (MI criteria can make radar echoes contain more multiple-target information and improve radar performance as a result.

  16. Neonatal morbidity associated with shoulder dystocia maneuvers.

    Spain, Janine E; Frey, Heather A; Tuuli, Methodius G; Colvin, Ryan; Macones, George A; Cahill, Alison G

    2015-03-01

    We sought to examine neonatal morbidity associated with different maneuvers used among term patients who experience a shoulder dystocia. We conducted a retrospective cohort study of all women who experienced a clinically diagnosed shoulder dystocia at term requiring obstetric maneuvers at a single tertiary care hospital from 2005 through 2008. We excluded women with major fetal anomaly, intrauterine death, multiple gestation, and preterm. Women exposed to Rubin maneuver, Wood's screw maneuver, or delivery of the posterior arm were compared to women delivered by McRoberts/suprapubic pressure only, which served as the reference group. The primary outcome was a composite morbidity of neonatal injury (defined as clavicular or humeral fracture or brachial plexus injury) and neonatal depression (defined as Apgar dystocia, defined as time from delivery of fetal head to delivery of shoulders. Among the 231 women who met inclusion criteria, 135 were delivered by McRoberts/suprapubic pressure alone (57.9%), 83 women were exposed to Rubin maneuver, 53 women were exposed to Wood's screw, and 36 women were exposed to delivery of posterior arm. Individual maneuvers were not associated with composite morbidity, neonatal injury, or neonatal depression after adjusting for nulliparity and duration of shoulder dystocia. We found no association between shoulder dystocia maneuvers and neonatal morbidity after adjusting for duration, a surrogate for severity. Our results demonstrate that clinicians should utilize the maneuver most likely to result in successful delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Maneuver Automation Software

    Uffelman, Hal; Goodson, Troy; Pellegrin, Michael; Stavert, Lynn; Burk, Thomas; Beach, David; Signorelli, Joel; Jones, Jeremy; Hahn, Yungsun; Attiyah, Ahlam; hide

    2009-01-01

    The Maneuver Automation Software (MAS) automates the process of generating commands for maneuvers to keep the spacecraft of the Cassini-Huygens mission on a predetermined prime mission trajectory. Before MAS became available, a team of approximately 10 members had to work about two weeks to design, test, and implement each maneuver in a process that involved running many maneuver-related application programs and then serially handing off data products to other parts of the team. MAS enables a three-member team to design, test, and implement a maneuver in about one-half hour after Navigation has process-tracking data. MAS accepts more than 60 parameters and 22 files as input directly from users. MAS consists of Practical Extraction and Reporting Language (PERL) scripts that link, sequence, and execute the maneuver- related application programs: "Pushing a single button" on a graphical user interface causes MAS to run navigation programs that design a maneuver; programs that create sequences of commands to execute the maneuver on the spacecraft; and a program that generates predictions about maneuver performance and generates reports and other files that enable users to quickly review and verify the maneuver design. MAS can also generate presentation materials, initiate electronic command request forms, and archive all data products for future reference.

  18. Memory for found targets interferes with subsequent performance in multiple-target visual search.

    Cain, Matthew S; Mitroff, Stephen R

    2013-10-01

    Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  19. Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

    Lu Zhang

    2012-01-01

    Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

  20. A mathematical analysis of multiple-target SELEX.

    Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

    2010-10-01

    SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following

  1. A compound chimeric antigen receptor strategy for targeting multiple myeloma.

    Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

    2018-02-01

    Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

  2. Multiple operating system rotation environment moving target defense

    Evans, Nathaniel; Thompson, Michael

    2016-03-22

    Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

  3. A multiple sampling ionization chamber for the External Target Facility

    Zhang, X.H.; Tang, S.W.; Ma, P.; Lu, C.G.; Yang, H.R.; Wang, S.T.; Yu, Y.H.; Yue, K.; Fang, F.; Yan, D.; Zhou, Y.; Wang, Z.M.; Sun, Y.; Sun, Z.Y.; Duan, L.M.; Sun, B.H.

    2015-01-01

    A multiple sampling ionization chamber used as a particle identification device for high energy heavy ions has been developed for the External Target Facility. The performance of this detector was tested with a 239 Pu α source and RI beams. A Z resolution (FWHM) of 0.4–0.6 was achieved for nuclear fragments of 18 O at 400 AMeV

  4. Maneuver from the Air Domain

    2016-05-26

    Overload From the previous discussion, cognitive maneuver seeks to degrade the enemy’s capacity for...in all domains, the ability to maneuver from the air domain in the cognitive sense, comes primarily from air power’s unique ability to overload the... cognitive maneuver mechanisms developed in the 1980s as part of broader maneuver warfare theory. The result is a proposed definition of maneuver from

  5. Cooperative multi-robot observation of multiple moving targets

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

    1997-01-01

    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. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

    Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

    2015-01-01

    BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

  7. Linking spatial and dynamic models for traffic maneuvers

    Olderog, Ernst-Rüdiger; Ravn, Anders Peter; Wisniewski, Rafal

    2015-01-01

    For traffic maneuvers of multiple vehicles on highways we build an abstract spatial and a concrete dynamic model. In the spatial model we show the safety (collision freedom) of lane-change maneuvers. By linking the spatial and dynamic model via suitable refinements of the spatial atoms to distance...

  8. Adaptive Maneuvering Frequency Method of Current Statistical Model

    Wei Sun; Yongjian Yang

    2017-01-01

    Current statistical model(CSM) has a good performance in maneuvering target tracking. However, the fixed maneuvering frequency will deteriorate the tracking results, such as a serious dynamic delay, a slowly converging speedy and a limited precision when using Kalman filter(KF) algorithm. In this study, a new current statistical model and a new Kalman filter are proposed to improve the performance of maneuvering target tracking. The new model which employs innovation dominated subjection function to adaptively adjust maneuvering frequency has a better performance in step maneuvering target tracking, while a fluctuant phenomenon appears. As far as this problem is concerned, a new adaptive fading Kalman filter is proposed as well. In the new Kalman filter, the prediction values are amended in time by setting judgment and amendment rules,so that tracking precision and fluctuant phenomenon of the new current statistical model are improved. The results of simulation indicate the effectiveness of the new algorithm and the practical guiding significance.

  9. Volumetric PIV of multiple free-swimming maneuvers generated by the KnifeBot: a biomimetic vessel propelled by an undulating fin

    Liu, Hanlin; Troolin, Daniel; Hortensius, Ruben; Pothos, Stamatios; Curet, Oscar

    2017-11-01

    An undulating fin represents a remarkable propulsion model for underwater vehicles due to its high propulsive efficiency and considerable locomotor capabilities. In this work, we used a bio-inspired vessel, the KnifeBot to demonstrate the maneuverability of undulating fin propulsion, including forward-backward swimming, station keeping and vertical swimming. This self-contained robotic system uses an undulating ventral fin as the propulsor and features a slender 3D-printed hull with 16 motors, 2 batteries and electronic boards encapsulated inside. We tested the robot in a water-filled tank and used volumetric particle image velocimetry (V3V PIV) to investigate the three-dimensional flow features and vortex structures generated by the undulating ribbon fin in free-swimming maneuvers. Our results indicate that in the forward swimming, a series of vortex tubes are shed off the fin edge. A streamwise jet at an oblique angle to the fin is generated in association with the vortex tubes propelling the robot forward as well as pitching it up. For the hovering maneuver with inward counter-propagating waves. The streamlines develop vertically downward with the tip vortex shed from the fin edge. This downward jet provides substantial heave force for the robot to swim upward or perform station keeping. Our findings will be useful for understanding the mechanical basis of undulating fin propulsion and facilitate the development of bio-inspired vehicles using undulatory propellers. Office of Naval Research under Award Number N00014-16-1-2505.

  10. A global calibration method for multiple vision sensors based on multiple targets

    Liu, Zhen; Zhang, Guangjun; Wei, Zhenzhong; Sun, Junhua

    2011-01-01

    The global calibration of multiple vision sensors (MVS) has been widely studied in the last two decades. In this paper, we present a global calibration method for MVS with non-overlapping fields of view (FOVs) using multiple targets (MT). MT is constructed by fixing several targets, called sub-targets, together. The mutual coordinate transformations between sub-targets need not be known. The main procedures of the proposed method are as follows: one vision sensor is selected from MVS to establish the global coordinate frame (GCF). MT is placed in front of the vision sensors for several (at least four) times. Using the constraint that the relative positions of all sub-targets are invariant, the transformation matrix from the coordinate frame of each vision sensor to GCF can be solved. Both synthetic and real experiments are carried out and good result is obtained. The proposed method has been applied to several real measurement systems and shown to be both flexible and accurate. It can serve as an attractive alternative to existing global calibration methods

  11. General and Specific Strategies Used to Facilitate Locomotor Maneuvers.

    Mengnan Wu

    Full Text Available People make anticipatory changes in gait patterns prior to initiating a rapid change of direction. How they prepare will change based on their knowledge of the maneuver. To investigate specific and general strategies used to facilitate locomotor maneuvers, we manipulated subjects' ability to anticipate the direction of an upcoming lateral "lane-change" maneuver. To examine specific anticipatory adjustments, we observed the four steps immediately preceding a maneuver that subjects were instructed to perform at a known time in a known direction. We hypothesized that to facilitate a specific change of direction, subjects would proactively decrease margin of stability in the future direction of travel. Our results support this hypothesis: subjects significantly decreased lateral margin of stability by 69% on the side ipsilateral to the maneuver during only the step immediately preceding the maneuver. This gait adaptation may have improved energetic efficiency and simplified the control of the maneuver. To examine general anticipatory adjustments, we observed the two steps immediately preceding the instant when subjects received information about the direction of the maneuver. When the maneuver direction was unknown, we hypothesized that subjects would make general anticipatory adjustments that would improve their ability to actively initiate a maneuver in multiple directions. This second hypothesis was partially supported as subjects increased step width and stance phase hip flexion during these anticipatory steps. These modifications may have improved subjects' ability to generate forces in multiple directions and maintain equilibrium during the onset and execution of the rapid maneuver. However, adapting these general anticipatory strategies likely incurred an additional energetic cost.

  12. Ground Target Overflight and Orbital Maneuvering via Atmospheric Maneuvers

    2014-03-27

    Total deceleration m ∙ s−2 Gravitational acceleration m ∙ s−2 ℎ Altitude m Inclination angle rad Vehicle mass kg Geocentric ...total atmospheric inclination change approached the limit of approximately 36.2° as the number of atmospheric passes increased. This inclination...determine the longitude. By expanding and simplifying Eqs. (3.1) and (3.5) for a circular orbit, the position can be written in the Geocentric Equatorial

  13. Targeting multiple heterogeneous hardware platforms with OpenCL

    Fox, Paul A.; Kozacik, Stephen T.; Humphrey, John R.; Paolini, Aaron; Kuller, Aryeh; Kelmelis, Eric J.

    2014-06-01

    The OpenCL API allows for the abstract expression of parallel, heterogeneous computing, but hardware implementations have substantial implementation differences. The abstractions provided by the OpenCL API are often insufficiently high-level to conceal differences in hardware architecture. Additionally, implementations often do not take advantage of potential performance gains from certain features due to hardware limitations and other factors. These factors make it challenging to produce code that is portable in practice, resulting in much OpenCL code being duplicated for each hardware platform being targeted. This duplication of effort offsets the principal advantage of OpenCL: portability. The use of certain coding practices can mitigate this problem, allowing a common code base to be adapted to perform well across a wide range of hardware platforms. To this end, we explore some general practices for producing performant code that are effective across platforms. Additionally, we explore some ways of modularizing code to enable optional optimizations that take advantage of hardware-specific characteristics. The minimum requirement for portability implies avoiding the use of OpenCL features that are optional, not widely implemented, poorly implemented, or missing in major implementations. Exposing multiple levels of parallelism allows hardware to take advantage of the types of parallelism it supports, from the task level down to explicit vector operations. Static optimizations and branch elimination in device code help the platform compiler to effectively optimize programs. Modularization of some code is important to allow operations to be chosen for performance on target hardware. Optional subroutines exploiting explicit memory locality allow for different memory hierarchies to be exploited for maximum performance. The C preprocessor and JIT compilation using the OpenCL runtime can be used to enable some of these techniques, as well as to factor in hardware

  14. Aliskiren targets multiple systems to alleviate cancer cachexia.

    Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua

    2016-11-01

    To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).

  15. Optimizing megakaryocyte polyploidization by targeting multiple pathways of cytokinesis.

    Avanzi, Mauro P; Chen, Amanda; He, Wu; Mitchell, W Beau

    2012-11-01

    Large-scale in vitro production of platelets (PLTs) from cord blood stem cells is one goal of stem cell research. One step toward this goal will be to produce polyploid megakaryocytes capable of releasing high numbers of PLTs. Megakaryocyte polyploidization requires distinct cytoskeletal and cellular mechanisms, including actin polymerization, myosin activation, microtubule formation, and increased DNA production. In this study we variably combined inhibition of these principal mechanisms of cytokinesis with the goal of driving polyploidization in megakaryocytes. Megakaryocytes were derived from umbilical cord blood and cultured with reagents that inhibit distinct mechanisms of cytokinesis: Rho-Rock inhibitor (RRI), Src inhibitor (SI), nicotinamide (NIC), aurora B inhibitor (ABI), and myosin light chain kinase inhibitor (MLCKI). Combinations of reagents were used to determine their interactions and to maximize megakaryocyte ploidy. Treatment with RRI, NIC, SI, and ABI, but not with MLCKI, increased the final ploidy and RRI was the most effective single reagent. RRI and MLCKI, both inhibitors of MLC activation, resulted in opposite ploidy outcomes. Combinations of reagents also increased ploidy and the use of NIC, SI, and ABI was as effective as RRI alone. Addition of MLCKI to NIC, SI, and ABI reached the highest level of polyploidization. Megakaryocyte polyploidization results from modulation of a combination of distinct cytokinesis pathways. Reagents targeting distinct cytoskeletal pathways produced additive effects in final megakaryocyte ploidy. The RRI, however, showed no additive effect but produced a high final ploidy due to overlapping inhibition of multiple cytokinesis pathways. © 2012 American Association of Blood Banks.

  16. Global Calibration of Multiple Cameras Based on Sphere Targets

    Junhua Sun

    2016-01-01

    Full Text Available Global calibration methods for multi-camera system are critical to the accuracy of vision measurement. Proposed in this paper is such a method based on several groups of sphere targets and a precision auxiliary camera. Each camera to be calibrated observes a group of spheres (at least three, while the auxiliary camera observes all the spheres. The global calibration can be achieved after each camera reconstructs the sphere centers in its field of view. In the process of reconstructing a sphere center, a parameter equation is used to describe the sphere projection model. Theoretical analysis and computer simulation are carried out to analyze the factors that affect the calibration accuracy. Simulation results show that the parameter equation can largely improve the reconstruction accuracy. In the experiments, a two-camera system calibrated by our method is used to measure a distance about 578 mm, and the root mean squared error is within 0.14 mm. Furthermore, the experiments indicate that the method has simple operation and good flexibility, especially for the onsite multiple cameras without common field of view.

  17. The meninges: new therapeutic targets for multiple sclerosis.

    Russi, Abigail E; Brown, Melissa A

    2015-02-01

    The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Multiple target sound quality balance for hybrid electric powertrain noise

    Mosquera-Sánchez, J. A.; Sarrazin, M.; Janssens, K.; de Oliveira, L. P. R.; Desmet, W.

    2018-01-01

    The integration of the electric motor to the powertrain in hybrid electric vehicles (HEVs) presents acoustic stimuli that elicit new perceptions. The large number of spectral components, as well as the wider bandwidth of this sort of noises, pose new challenges to current noise, vibration and harshness (NVH) approaches. This paper presents a framework for enhancing the sound quality (SQ) of the hybrid electric powertrain noise perceived inside the passenger compartment. Compared with current active sound quality control (ASQC) schemes, where the SQ improvement is just an effect of the control actions, the proposed technique features an optimization stage, which enables the NVH specialist to actively implement the amplitude balance of the tones that better fits into the auditory expectations. Since Loudness, Roughness, Sharpness and Tonality are the most relevant SQ metrics for interior HEV noise, they are used as performance metrics in the concurrent optimization analysis, which, eventually, drives the control design method. Thus, multichannel active sound profiling systems that feature cross-channel compensation schemes are guided by the multi-objective optimization stage, by means of optimal sets of amplitude gain factors that can be implemented at each single sensor location, while minimizing cross-channel effects that can either degrade the original SQ condition, or even hinder the implementation of independent SQ targets. The proposed framework is verified experimentally, with realistic stationary hybrid electric powertrain noise, showing SQ enhancement for multiple locations within a scaled vehicle mock-up. The results show total success rates in excess of 90%, which indicate that the proposed method is promising, not only for the improvement of the SQ of HEV noise, but also for a variety of periodic disturbances with similar features.

  19. Multiple Model Particle Filtering For Multi-Target Tracking

    Hero, Alfred; Kreucher, Chris; Kastella, Keith

    2004-01-01

    .... The details of this method have been presented elsewhere 1. One feature of real targets is that they are poorly described by a single kinematic model Target behavior may change dramatically i.e...

  20. Realization of quantum gates with multiple control qubits or multiple target qubits in a cavity

    Waseem, Muhammad; Irfan, Muhammad; Qamar, Shahid

    2015-06-01

    We propose a scheme to realize a three-qubit controlled phase gate and a multi-qubit controlled NOT gate of one qubit simultaneously controlling n-target qubits with a four-level quantum system in a cavity. The implementation time for multi-qubit controlled NOT gate is independent of the number of qubit. Three-qubit phase gate is generalized to n-qubit phase gate with multiple control qubits. The number of steps reduces linearly as compared to conventional gate decomposition method. Our scheme can be applied to various types of physical systems such as superconducting qubits coupled to a resonator and trapped atoms in a cavity. Our scheme does not require adjustment of level spacing during the gate implementation. We also show the implementation of Deutsch-Joza algorithm. Finally, we discuss the imperfections due to cavity decay and the possibility of physical implementation of our scheme.

  1. Constellation Mission Operation Working Group: ESMO Maneuver Planning Process Review

    Moyer, Eric

    2015-01-01

    The Earth Science Mission Operation (ESMO) Project created an Independent Review Board to review our Conjunction Risk evaluation process and Maneuver Planning Process to identify improvements that safely manages mission conjunction risks, maintains ground track science requirements, and minimizes overall hours expended on High Interest Events (HIE). The Review Board is evaluating the current maneuver process which requires support by multiple groups. In the past year, there have been several changes to the processes although many prior and new concerns exist. This presentation will discuss maneuver process reviews and Board comments, ESMO assessment and path foward, ESMO future plans, recent changes and concerns.

  2. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  3. Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

    Kwok, Kwan S.; Driessen, Brian J.; Phillips, Cynthia A.; Tovey, Craig A.

    1997-09-01

    This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. We wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which we must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solution times for one hundred robots took only seconds on a silicon graphics crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. We have found these mobile robot problems to be a very interesting application of network optimization methods, and we expect this to be a fruitful area for future research.

  4. Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

    Kwok, K.S.; Driessen, B.J.; Phillips, C.A.; Tovey, C.A.

    1997-01-01

    This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. The authors wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which they must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solutions times for one hundred robots took only seconds on a Silicon Graphics Crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. They have found these mobile robot problems to be a very interesting application of network optimization methods, and they expect this to be a fruitful area for future research

  5. Tracking a convoy of multiple targets using acoustic sensor data

    Damarla, T. R.

    2003-08-01

    In this paper we present an algorithm to track a convoy of several targets in a scene using acoustic sensor array data. The tracking algorithm is based on template of the direction of arrival (DOA) angles for the leading target. Often the first target is the closest target to the sensor array and hence the loudest with good signal to noise ratio. Several steps were used to generate a template of the DOA angle for the leading target, namely, (a) the angle at the present instant should be close to the angle at the previous instant and (b) the angle at the present instant should be within error bounds of the predicted value based on the previous values. Once the template of the DOA angles of the leading target is developed, it is used to predict the DOA angle tracks of the remaining targets. In order to generate the tracks for the remaining targets, a track is established if the angles correspond to the initial track values of the first target. Second the time delay between the first track and the remaining tracks are estimated at the highest correlation points between the first track and the remaining tracks. As the vehicles move at different speeds the tracks either compress or expand depending on whether a target is moving fast or slow compared to the first target. The expansion and compression ratios are estimated and used to estimate the predicted DOA angle values of the remaining targets. Based on these predicted DOA angles of the remaining targets the DOA angles obtained from the MVDR or Incoherent MUSIC will be appropriately assigned to proper tracks. Several other rules were developed to avoid mixing the tracks. The algorithm is tested on data collected at Aberdeen Proving Ground with a convoy of 3, 4 and 5 vehicles. Some of the vehicles are tracked and some are wheeled vehicles. The tracking algorithm results are found to be good. The results will be presented at the conference and in the paper.

  6. Support and maneuvering device

    Wood, R.L.

    1987-03-23

    A support and maneuvering device includes an elongated flexible inflatable enclosure having a fixed end and a movable end. The movable end is collapsible toward the fixed end to a contracted position when the enclosure is in a noninflated condition. Upon inflation, the movable end is movable away from the fixed end to an extended position. The movable end includes means for mounting an article such as a solar reflector thereon. The device also includes a plurality of position controlling means disposed about the movable end to effect adjusting movement of portions thereof by predetermined amounts and for controlling an angle at which the article disposed at the movable end is oriented. The plurality of position controlling means limits a suitable number degrees of freedom of the movable end for transmitting a steering motion thereto and for controlling the position thereof. 9 figs.

  7. Mars Exploration Rovers Propulsive Maneuver Design

    Potts, Christopher L.; Raofi, Behzad; Kangas, Julie A.

    2004-01-01

    The Mars Exploration Rovers Spirit and Opportunity successfully landed respectively at Gusev Crater and Meridiani Planum in January 2004. The rovers are essentially robotic geologists, sent on a mission to search for evidence in the rocks and soil pertaining to the historical presence of water and the ability to possibly sustain life. In order to conduct NASA's 'follow the water' strategy on opposite sides of the planet Mars, an interplanetary journey of over 300 million miles culminated with historic navigation precision. Rigorous trajectory targeting and control was necessary to achieve the atmospheric entry requirements for the selected landing sites. The propulsive maneuver design challenge was to meet or exceed these requirements while preserving the necessary design margin to accommodate additional project concerns. Landing site flexibility was maintained for both missions after launch, and even after the first trajectory correction maneuver for Spirit. The final targeting strategy was modified to improve delivery performance and reduce risk after revealing constraining trajectory control characteristics. Flight results are examined and summarized for the six trajectory correction maneuvers that were planned for each mission.

  8. Random Scenario Generation for a Multiple Target Tracking Environment Evaluation

    Hussain, Dil Muhammad Akbar

    2006-01-01

    , which were normally crossing targets, was to test the efficiency of the track splitting algorithm for different situations. However this approach only gives a measure of performance for a specific, possibly unrealistic, scenario and it was felt appropriate to develop procedures that would enable a more...... general performance assessment. Therefore, a random target motion scenario is adopted. Its implementation in particular for testing the track splitting algorithm using Kalman filters is used and a couple of tracking performance parameters are computed to investigate such random scenarios....

  9. Five kepler target stars that show multiple transiting exoplanet candidates

    Steffen..[], Jason H.; Batalha, N. M.; Broucki, W J.

    2010-01-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets a...

  10. Interleukin-6, a new target for therapy in multiple myeloma?

    van Oers, M. H.; van Zaanen, H. C.; Lokhorst, H. M.

    1993-01-01

    During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo

  11. THE DUBINS TRAVELING SALESMAN PROBLEM WITH CONSTRAINED COLLECTING MANEUVERS

    Petr Váňa

    2016-11-01

    Full Text Available In this paper, we introduce a variant of the Dubins traveling salesman problem (DTSP that is called the Dubins traveling salesman problem with constrained collecting maneuvers (DTSP-CM. In contrast to the ordinary formulation of the DTSP, in the proposed DTSP-CM, the vehicle is requested to visit each target by specified collecting maneuver to accomplish the mission. The proposed problem formulation is motivated by scenarios with unmanned aerial vehicles where particular maneuvers are necessary for accomplishing the mission, such as object dropping or data collection with sensor sensitive to changes in vehicle heading. We consider existing methods for the DTSP and propose its modifications to use these methods to address a variant of the introduced DTSP-CM, where the collecting maneuvers are constrained to straight line segments.

  12. Autonomous Shepherding Behaviors of Multiple Target Steering Robots.

    Lee, Wonki; Kim, DaeEun

    2017-11-25

    This paper presents a distributed coordination methodology for multi-robot systems, based on nearest-neighbor interactions. Among many interesting tasks that may be performed using swarm robots, we propose a biologically-inspired control law for a shepherding task, whereby a group of external agents drives another group of agents to a desired location. First, we generated sheep-like robots that act like a flock. We assume that each agent is capable of measuring the relative location and velocity to each of its neighbors within a limited sensing area. Then, we designed a control strategy for shepherd-like robots that have information regarding where to go and a steering ability to control the flock, according to the robots' position relative to the flock. We define several independent behavior rules; each agent calculates to what extent it will move by summarizing each rule. The flocking sheep agents detect the steering agents and try to avoid them; this tendency leads to movement of the flock. Each steering agent only needs to focus on guiding the nearest flocking agent to the desired location. Without centralized coordination, multiple steering agents produce an arc formation to control the flock effectively. In addition, we propose a new rule for collecting behavior, whereby a scattered flock or multiple flocks are consolidated. From simulation results with multiple robots, we show that each robot performs actions for the shepherding behavior, and only a few steering agents are needed to control the whole flock. The results are displayed in maps that trace the paths of the flock and steering robots. Performance is evaluated via time cost and path accuracy to demonstrate the effectiveness of this approach.

  13. Autonomous Shepherding Behaviors of Multiple Target Steering Robots

    Wonki Lee

    2017-11-01

    Full Text Available This paper presents a distributed coordination methodology for multi-robot systems, based on nearest-neighbor interactions. Among many interesting tasks that may be performed using swarm robots, we propose a biologically-inspired control law for a shepherding task, whereby a group of external agents drives another group of agents to a desired location. First, we generated sheep-like robots that act like a flock. We assume that each agent is capable of measuring the relative location and velocity to each of its neighbors within a limited sensing area. Then, we designed a control strategy for shepherd-like robots that have information regarding where to go and a steering ability to control the flock, according to the robots’ position relative to the flock. We define several independent behavior rules; each agent calculates to what extent it will move by summarizing each rule. The flocking sheep agents detect the steering agents and try to avoid them; this tendency leads to movement of the flock. Each steering agent only needs to focus on guiding the nearest flocking agent to the desired location. Without centralized coordination, multiple steering agents produce an arc formation to control the flock effectively. In addition, we propose a new rule for collecting behavior, whereby a scattered flock or multiple flocks are consolidated. From simulation results with multiple robots, we show that each robot performs actions for the shepherding behavior, and only a few steering agents are needed to control the whole flock. The results are displayed in maps that trace the paths of the flock and steering robots. Performance is evaluated via time cost and path accuracy to demonstrate the effectiveness of this approach.

  14. Orbital maneuvering end effectors

    Myers, W. Neill (Inventor); Forbes, John C. (Inventor); Barnes, Wayne L. (Inventor)

    1986-01-01

    This invention relates to an end effector device for grasping and maneuvering objects such as berthing handles of a space telescope. The device includes a V-shaped capture window defined as inclined surfaces in parallel face plates which converge toward a retainer recess in which the handle is retained. A pivotal finger (30) meshes with a pair of pivoted fingers which rotate in counterrotation. The fingers rotate to pull a handle within the capture window into recess where latches lock handle in the recess. To align the capture window, plates may be cocked plus or minus five degrees on base. Drive means is included in the form of a motor coupled with a harmonic drive speed reducer, which provides for slow movement of the fingers at a high torque so that large articles may be handled. Novelty of the invention is believed to reside in the combined intermeshing finger structure, drive means and the harmonic drive speed reducer, which features provide the required maneuverability and strength.

  15. Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

    Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

    2016-01-01

    Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

  16. Five Kepler target stars that show multiple transiting exoplanet candidates

    Steffen, Jason H.; /Fermilab; Batalha, Natalie M.; /San Jose State U.; Borucki, William J.; /NASA, Ames; Buchhave, Lars A.; /Harvard-Smithsonian Ctr. Astrophys. /Bohr Inst.; Caldwell, Douglas A.; /NASA, Ames /SETI Inst., Mtn. View; Cochran, William D.; /Texas U.; Endl, Michael; /Texas U.; Fabrycky, Daniel C.; /Harvard-Smithsonian Ctr. Astrophys.; Fressin, Francois; /Harvard-Smithsonian Ctr. Astrophys.; Ford, Eric B.; /Florida U.; Fortney, Jonathan J.; /UC, Santa Cruz, Phys. Dept. /NASA, Ames

    2010-06-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets and provide new insights into the formation and dynamical evolution of planetary systems. We discuss the methods used to identify multiple transiting objects from the Kepler photometry as well as the false-positive rejection methods that have been applied to these data. One system shows transits from three distinct objects while the remaining four systems show transits from two objects. Three systems have planet candidates that are near mean motion commensurabilities - two near 2:1 and one just outside 5:2. We discuss the implications that multitransiting systems have on the distribution of orbital inclinations in planetary systems, and hence their dynamical histories; as well as their likely masses and chemical compositions. A Monte Carlo study indicates that, with additional data, most of these systems should exhibit detectable transit timing variations (TTV) due to gravitational interactions - though none are apparent in these data. We also discuss new challenges that arise in TTV analyses due to the presence of more than two planets in a system.

  17. Gray Matter Is Targeted in First-Attack Multiple Sclerosis

    Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao; Schepmoes, Athena A.; Xie, Fang; Bergquist, Jonas P.; Vecsei, Lazlo' ; Zadori, Denes; Camp, David G.; Holland, Bart K.; Smith, Richard D.; Coyle, Patricia K.

    2013-09-10

    The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

  18. Circadian phase resetting via single and multiple control targets.

    Neda Bagheri

    2008-07-01

    Full Text Available Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, motivating its use as a key control input for phase resetting. Through sensitivity analysis, we identify additional control targets whose individual and simultaneous manipulation (via a model predictive control algorithm out-perform the open-loop light-based phase recovery dynamics by nearly 3-fold. We further demonstrate the robustness of phase resetting by synchronizing short- and long-period mutant phenotypes to the 24-hour environment; the control algorithm is robust in the presence of model mismatch. These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine. In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

  19. Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

    Rafael Lugo-Huitrón

    2013-01-01

    Full Text Available Quinolinic acid (QUIN, a neuroactive metabolite of the kynurenine pathway, is normally presented in nanomolar concentrations in human brain and cerebrospinal fluid (CSF and is often implicated in the pathogenesis of a variety of human neurological diseases. QUIN is an agonist of N-methyl-D-aspartate (NMDA receptor, and it has a high in vivo potency as an excitotoxin. In fact, although QUIN has an uptake system, its neuronal degradation enzyme is rapidly saturated, and the rest of extracellular QUIN can continue stimulating the NMDA receptor. However, its toxicity cannot be fully explained by its activation of NMDA receptors it is likely that additional mechanisms may also be involved. In this review we describe some of the most relevant targets of QUIN neurotoxicity which involves presynaptic receptors, energetic dysfunction, oxidative stress, transcription factors, cytoskeletal disruption, behavior alterations, and cell death.

  20. Romidepsin targets multiple survival signaling pathways in malignant T cells

    Valdez, B C; Brammer, J E; Li, Y; Murray, D; Liu, Y; Hosing, C; Nieto, Y; Champlin, R E; Andersson, B S

    2015-01-01

    Romidepsin is a cyclic molecule that inhibits histone deacetylases. It is Food and Drug Administration-approved for treatment of cutaneous and peripheral T-cell lymphoma, but its precise mechanism of action against malignant T cells is unknown. To better understand the biological effects of romidepsin in these cells, we exposed PEER and SUPT1 T-cell lines, and a primary sample from T-cell lymphoma patient (Patient J) to romidepsin. We then examined the consequences in some key oncogenic signaling pathways. Romidepsin displayed IC 50 values of 10.8, 7.9 and 7.0 nm in PEER, SUPT1 and Patient J cells, respectively. Strong inhibition of histone deacetylases and demethylases, increased production of reactive oxygen species and decreased mitochondrial membrane potential were observed, which may contribute to the observed DNA-damage response and apoptosis. The stress-activated protein kinase/c-Jun N-terminal kinase signaling pathway and unfolded protein response in the endoplasmic reticulum were activated, whereas the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and β-catenin pro-survival pathways were inhibited. The decreased level of β-catenin correlated with the upregulation of its inhibitor SFRP1 through romidepsin-mediated hypomethylation of its gene promoter. Our results provide new insights into how romidepsin invokes malignant T-cell killing, show evidence of its associated DNA hypomethylating activity and offer a rationale for the development of romidepsin-containing combination therapies

  1. Extending Data Worth Analyses to Select Multiple Observations Targeting Multiple Forecasts

    Vilhelmsen, Troels Norvin; Ferre, Ty Paul

    2017-01-01

    . In the present study, we extend previous data worth analyses to include: simultaneous selection of multiple new measurements and consideration of multiple forecasts of interest. We show how the suggested approach can be used to optimize data collection. This can be used in a manner that suggests specific...... measurement sets or that produces probability maps indicating areas likely to be informative for specific forecasts. Moreover, we provide examples documenting that sequential measurement election approaches often lead to suboptimal designs and that estimates of data covariance should be included when...

  2. Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis

    Al-Izki, S.; Pryce, G.; Hankey, D.J.R.; Lidster, K.; von Kutzleben, S.M.; Browne, L.; Clutterbuck, L.; Posada, C.; Chan, A.W.E.; Amor, S.; Perkins, V.; Gerritsen, W.H.; Ummenthum, K.; Peferoen-Baert, R.; van der Valk, P.; Montoya, A.; Joel, S.P.; Garthwaite, J.; Giovannoni, G.; Selwood, D.L.; Baker, D.

    2014-01-01

    Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to

  3. Multiple scattering in electron fluid and energy loss in multi-ionic targets

    Deutsch, C., E-mail: claude.deutsch@u-psud.fr [LPGP, UParis-Sud, 91405-Orsay (France); Tahir, N.A. [GSI, 1Planck Str., 64291-Darmstadt (Germany); Barriga-Carrasco, M. [ETSII, UCastilla-la-Mancha, 13071 Ciudad-Real (Spain); Ceban, V. [LPGP, UParis-Sud, 91405-Orsay (France); Fromy, P. [CRI, UParis-Sud, 91405-Orsay (France); Gilles, D. [CEA/Saclay/DSM/IRFU/SAP, 91191-Gif-s-Yvette (France); Leger, D. [Laboratoire Monthouy, UValenciennes-Hainaut Cambresis (France); Maynard, G. [LPGP, UParis-Sud, 91405-Orsay (France); Tashev, B. [Department of Physics, KazNu, Tole Bi82, Almaty (Kazakhstan); Volpe, L. [Department of Physics, UMilano-Bicocca, Milano 20126 (Italy)

    2014-01-01

    Extensions of the standard stopping model (SSM) for ion projectiles interacting with dense targets of timely concern for ICF and WDM are reviewed. They include multiple scattering on partially degenerate electrons, low velocity ion slowing down in demixing H–He mixtures within Jovian planets core or multiionic target such as Kapton.

  4. Multiple scattering in electron fluid and energy loss in multi-ionic targets

    Deutsch, C.; Tahir, N.A.; Barriga-Carrasco, M.; Ceban, V.; Fromy, P.; Gilles, D.; Leger, D.; Maynard, G.; Tashev, B.; Volpe, L.

    2014-01-01

    Extensions of the standard stopping model (SSM) for ion projectiles interacting with dense targets of timely concern for ICF and WDM are reviewed. They include multiple scattering on partially degenerate electrons, low velocity ion slowing down in demixing H–He mixtures within Jovian planets core or multiionic target such as Kapton

  5. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  6. Qualitative analysis of the Dix-Hallpike maneuver in multi-canal BPPV using a biomechanical model: Introduction of an expanded Dix-Hallpike maneuver for enhanced diagnosis of multi-canal BPPV

    Henri Traboulsi

    2017-09-01

    Conclusion: The Dix–Hallpike maneuver may cause simultaneous movement of otoliths present in multiple canals and create an obstacle to accurate diagnosis in multi-canal BPPV. An expanded Dix-Hallpike maneuver is described which adds intermediate steps with the head positioned to the right and left in the horizontal position before head-hanging. This expanded maneuver has helped to isolate affected semi-circular canals for individual assessment in multiple canal BPPV.

  7. Irradiation uniformity of spherical targets by multiple uv beams from OMEGA

    Beich, W.; Dunn, M.; Hutchison, R.

    1984-01-01

    Direct-drive laser fusion demands extremely high levels of irradiation uniformity to ensure uniform compression of spherical targets. The assessment of illumination uniformity of targets irradiated by multiple beams from the OMEGA facility is made with the aid of multiple beams spherical superposition codes, which take into account ray tracing and absorption and a detailed knowledge of the intensity distribution of each beam in the target plane. In this report, recent estimates of the irradiation uniformity achieved with 6 and 12 uv beams of OMEGA will be compared with previous measurements in the IR, and predictions will be made for the uv illumination uniformity achievable with 24 beams of OMEGA

  8. Extending Data Worth Analyses to Select Multiple Observations Targeting Multiple Forecasts.

    Vilhelmsen, Troels N; Ferré, Ty P A

    2017-09-15

    Hydrological models are often set up to provide specific forecasts of interest. Owing to the inherent uncertainty in data used to derive model structure and used to constrain parameter variations, the model forecasts will be uncertain. Additional data collection is often performed to minimize this forecast uncertainty. Given our common financial restrictions, it is critical that we identify data with maximal information content with respect to forecast of interest. In practice, this often devolves to qualitative decisions based on expert opinion. However, there is no assurance that this will lead to optimal design, especially for complex hydrogeological problems. Specifically, these complexities include considerations of multiple forecasts, shared information among potential observations, information content of existing data, and the assumptions and simplifications underlying model construction. In the present study, we extend previous data worth analyses to include: simultaneous selection of multiple new measurements and consideration of multiple forecasts of interest. We show how the suggested approach can be used to optimize data collection. This can be used in a manner that suggests specific measurement sets or that produces probability maps indicating areas likely to be informative for specific forecasts. Moreover, we provide examples documenting that sequential measurement election approaches often lead to suboptimal designs and that estimates of data covariance should be included when selecting future measurement sets. © 2017, National Ground Water Association.

  9. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

    2017-01-01

    Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

  10. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Leslie Regad

    Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

  11. Improved Maneuver Criteria Evaluation Program

    1979-11-01

    If the rotor rpm breakpoint (OMGBL2) is le :-s than the mininum rotor rpm (OMEGMN), then the rpm bleed :ate (OMGBDI) will be the only bleed rate used...VCP =60 PSU 1 EEF = 1 OMGBD1=2 OMGBD3=0 OMGRC2=0 VERR = 2 MPRINT= 1 OMEGMN=300 OMGBL.2=4 OMGBL4=0 OMGRD2=0 MUF = 1 BINERT:2860 TRPMMN= 0 OMGBD2=0 OMGBD4...height is within 2 feet of the measured height. These comparisons show that the MCEP maneuvers are accurate for simulating these types of maneuvers

  12. An overview of Suomi NPP VIIRS calibration maneuvers

    Butler, James J.; Xiong, Xiaoxiong; Barnes, Robert A.; Patt, Frederick S.; Sun, Junqiang; Chiang, Kwofu

    2012-09-01

    The first Visible Infrared Imager Radiometer Suite (VIIRS) instrument was successfully launched on-board the Suomi National Polar-orbiting Partnership (SNPP) spacecraft on October 28, 2011. Suomi NPP VIIRS observations are made in 22 spectral bands, from the visible (VIS) to the long-wave infrared (LWIR), and are used to produce 22 Environmental Data Records (EDRs) with a broad range of scientific applications. The quality of these VIIRS EDRs strongly depends on the quality of its calibrated and geo-located Sensor Date Records (SDRs). Built with a strong heritage to the NASA's EOS MODerate resolution Imaging Spectroradiometer (MODIS) instrument, the VIIRS is calibrated on-orbit using a similar set of on-board calibrators (OBC), including a solar diffuser (SD) and solar diffuser stability monitor (SDSM) system for the reflective solar bands (RSB) and a blackbody (BB) for the thermal emissive bands (TEB). Onorbit maneuvers of the SNPP spacecraft provide additional calibration and characterization data from the VIIRS instrument which cannot be obtained pre-launch and are required to produce the highest quality SDRs. These include multiorbit yaw maneuvers for the characterization of SD and SDSM screen transmission, quasi-monthly roll maneuvers to acquire lunar observations to track sensor degradation in the visible through shortwave infrared, and a driven pitch-over maneuver to acquire multiple scans of deep space to determine TEB response versus scan angle (RVS). This paper provides an overview of these three SNPP calibration maneuvers. Discussions are focused on their potential calibration and science benefits, pre-launch planning activities, and on-orbit scheduling and implementation strategies. Results from calibration maneuvers performed during the Intensive Calibration and Validation (ICV) period for the VIIRS sensor are illustrated. Also presented in this paper are lessons learned regarding the implementation of calibration spacecraft maneuvers on follow

  13. A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

    Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

    2017-03-31

    The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

  14. Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

    Wang, Ying; Li, Zhaohui; Liu, Misha; Hu, Dehong; Lin, Yuehe; Li, Jinghong

    2017-08-29

    Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

  15. Rendezvous maneuvers using Genetic Algorithm

    Dos Santos, Denílson Paulo Souza; De Almeida Prado, Antônio F Bertachini; Teodoro, Anderson Rodrigo Barretto

    2013-01-01

    The present paper has the goal of studying orbital maneuvers of Rendezvous, that is an orbital transfer where a spacecraft has to change its orbit to meet with another spacecraft that is travelling in another orbit. This transfer will be accomplished by using a multi-impulsive control. A genetic algorithm is used to find the transfers that have minimum fuel consumption

  16. Through-Wall Multiple Targets Vital Signs Tracking Based on VMD Algorithm

    Jiaming Yan

    2016-08-01

    Full Text Available Targets located at the same distance are easily neglected in most through-wall multiple targets detecting applications which use the single-input single-output (SISO ultra-wideband (UWB radar system. In this paper, a novel multiple targets vital signs tracking algorithm for through-wall detection using SISO UWB radar has been proposed. Taking advantage of the high-resolution decomposition of the Variational Mode Decomposition (VMD based algorithm, the respiration signals of different targets can be decomposed into different sub-signals, and then, we can track the time-varying respiration signals accurately when human targets located in the same distance. Intensive evaluation has been conducted to show the effectiveness of our scheme with a 0.15 m thick concrete brick wall. Constant, piecewise-constant and time-varying vital signs could be separated and tracked successfully with the proposed VMD based algorithm for two targets, even up to three targets. For the multiple targets’ vital signs tracking issues like urban search and rescue missions, our algorithm has superior capability in most detection applications.

  17. Morphology, muscle capacity, skill, and maneuvering ability in hummingbirds.

    Dakin, Roslyn; Segre, Paolo S; Straw, Andrew D; Altshuler, Douglas L

    2018-02-09

    How does agility evolve? This question is challenging because natural movement has many degrees of freedom and can be influenced by multiple traits. We used computer vision to record thousands of translations, rotations, and turns from more than 200 hummingbirds from 25 species, revealing that distinct performance metrics are correlated and that species diverge in their maneuvering style. Our analysis demonstrates that the enhanced maneuverability of larger species is explained by their proportionately greater muscle capacity and lower wing loading. Fast acceleration maneuvers evolve by recruiting changes in muscle capacity, whereas fast rotations and sharp turns evolve by recruiting changes in wing morphology. Both species and individuals use turns that play to their strengths. These results demonstrate how both skill and biomechanical traits shape maneuvering behavior. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. Dynamic studies of multiple configurations of CERN's Antiproton Decelerator Target core under proton beam impact

    AUTHOR|(CDS)2248381

    Antiprotons, like many other exotic particles, are produced by impacting high energy proton beams onto fixed targets. At the European Organization for Nuclear Research (CERN), this is done in the Antiproton Decelerator (AD) Facility. The engineering challenges related to the design of an optimal configuration of the AD-Target system derive from the extremely high energy depositions reached in the very thin target core as a consequence of each proton beam impact. A new target design is foreseen for operation after 2021, triggering multiple R&D activities since 2013 for this purpose. The goal of the present Master Thesis is to complement these activities with analytical and numerical calculations, delving into the phenomena associated to the dynamic response of the target core. In this context, two main studies have been carried out. First, the experimental data observed in targets subjected to low intensity proton pulses was cross-checked with analytical and computational methods for modal analysis, applie...

  19. Category-based attentional guidance can operate in parallel for multiple target objects.

    Jenkins, Michael; Grubert, Anna; Eimer, Martin

    2018-04-30

    The question whether the control of attention during visual search is always feature-based or can also be based on the category of objects remains unresolved. Here, we employed the N2pc component as an on-line marker for target selection processes to compare the efficiency of feature-based and category-based attentional guidance. Two successive displays containing pairs of real-world objects (line drawings of kitchen or clothing items) were separated by a 10 ms SOA. In Experiment 1, target objects were defined by their category. In Experiment 2, one specific visual object served as target (exemplar-based search). On different trials, targets appeared either in one or in both displays, and participants had to report the number of targets (one or two). Target N2pc components were larger and emerged earlier during exemplar-based search than during category-based search, demonstrating the superior efficiency of feature-based attentional guidance. On trials where target objects appeared in both displays, both targets elicited N2pc components that overlapped in time, suggesting that attention was allocated in parallel to these target objects. Critically, this was the case not only in the exemplar-based task, but also when targets were defined by their category. These results demonstrate that attention can be guided by object categories, and that this type of category-based attentional control can operate concurrently for multiple target objects. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. 33 CFR 84.23 - Maneuvering light.

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Maneuvering light. 84.23 Section... RULES ANNEX I: POSITIONING AND TECHNICAL DETAILS OF LIGHTS AND SHAPES § 84.23 Maneuvering light. Notwithstanding the provisions of § 84.03(f), the maneuvering light described in Rule 34(b) shall be placed...

  1. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

    2016-01-01

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

  2. Getting satisfied with "satisfaction of search": How to measure errors during multiple-target visual search.

    Biggs, Adam T

    2017-07-01

    Visual search studies are common in cognitive psychology, and the results generally focus upon accuracy, response times, or both. Most research has focused upon search scenarios where no more than 1 target will be present for any single trial. However, if multiple targets can be present on a single trial, it introduces an additional source of error because the found target can interfere with subsequent search performance. These errors have been studied thoroughly in radiology for decades, although their emphasis in cognitive psychology studies has been more recent. One particular issue with multiple-target search is that these subsequent search errors (i.e., specific errors which occur following a found target) are measured differently by different studies. There is currently no guidance as to which measurement method is best or what impact different measurement methods could have upon various results and conclusions. The current investigation provides two efforts to address these issues. First, the existing literature is reviewed to clarify the appropriate scenarios where subsequent search errors could be observed. Second, several different measurement methods are used with several existing datasets to contrast and compare how each method would have affected the results and conclusions of those studies. The evidence is then used to provide appropriate guidelines for measuring multiple-target search errors in future studies.

  3. Development of a Ground Vehicle Maneuver Ontology to Support the Common Operational Picture

    Richmond, Paul W; Blais, Curtis L; Goerger, Niki C

    2006-01-01

    .... This paper describes both the Mobility-COP, from which warfighters can assess the ability of forces to maneuver effectively under multiple environmental and tactical conditions, and a formal ontology...

  4. Detection and localization of multiple short range targets using FMCW radar signal

    Jardak, Seifallah

    2016-07-26

    In this paper, a 24 GHz frequency-modulated continuous wave radar is used to detect and localize both stationary and moving targets. Depending on the application, the implemented software offers different modes of operation. For example, it can simply output raw data samples for advanced offline processing or directly carry out a two dimensional fast Fourier transform to estimate the location and velocity of multiple targets. To suppress clutter and detect only moving targets, two methods based on the background reduction and the slow time processing techniques are implemented. A trade-off between the two methods is presented based on their performance and the required processing time. © 2016 IEEE.

  5. Multiple-target method for sputtering amorphous films for bubble-domain devices

    Burilla, C.T.; Bekebrede, W.R.; Smith, A.B.

    1976-01-01

    Previously, sputtered amorphous metal alloys for bubble applications have ordinarily been prepared by standard sputtering techniques using a single target electrode. The deposition of these alloys is reported using a multiple target rf technique in which a separate target is used for each element contained in the alloy. One of the main advantages of this multiple-target approach is that the film composition can be easily changed by simply varying the voltages applied to the elemental targets. In the apparatus, the centers of the targets are positioned on a 15 cm-radius circle. The platform holding the film substrate is on a 15 cm-long arm which can rotate about the center, thus bringing the sample successively under each target. The platform rotation rate is adjustable from 0 to 190 rpm. That this latter speed is sufficient to homogenize the alloys produced is demonstrated by measurements made of the uniaxial anisotropy constant in Gd 0 . 12 Co 0 . 59 Cu 0 . 29 films. The anisotropy is 6.0 x 10 5 ergs/cm 3 and independent of rotation rate above approximately 25 rpm, but it drops rapidly for slower rotation rates, reaching 1.8 x 10 5 ergs/cm 3 for 7 rpm. The film quality is equal to that of films made by conventional methods. Coercivities of a few oersteds in samples with stripe widths of 1 to 2 μm and magnetizations of 800 to 2800 G were observed

  6. Multiple-targeted graphene-based nanocarrier for intracellular imaging of mRNAs

    Wang, Ying; Li, Zhaohui; Liu, Misha; Xu, Jinjin; Hu, Dehong; Lin, Yuehe; Li, Jinghong

    2017-01-01

    Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labelled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis. - Graphical abstract: Schematic illustration of simultaneously multiple mRNAs monitoring inside single living breast cancer cell based on GO nanocarrier. In particular, the fluorescent signals could be monitored when Mn-SOD probe (red) and β-actin probe (green) hybridizes with their mRNA targets inside the living cells. Random probe (orange) was regarded as control probe for the sensing strategy. - Highlights: • A multiple-targeted GO nanocarrier was used for mRNAs imaging and expression changes after drug treatment can be monitored successfully. • Sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) m

  7. Intelligent Prediction of Ship Maneuvering

    Miroslaw Lacki

    2016-09-01

    Full Text Available In this paper the author presents an idea of the intelligent ship maneuvering prediction system with the usage of neuroevolution. This may be also be seen as the ship handling system that simulates a learning process of an autonomous control unit, created with artificial neural network. The control unit observes input signals and calculates the values of required parameters of the vessel maneuvering in confined waters. In neuroevolution such units are treated as individuals in population of artificial neural networks, which through environmental sensing and evolutionary algorithms learn to perform given task efficiently. The main task of the system is to learn continuously and predict the values of a navigational parameters of the vessel after certain amount of time, regarding an influence of its environment. The result of a prediction may occur as a warning to navigator to aware him about incoming threat.

  8. Dynamic sensor tasking and IMM EKF estimation for tracking impulsively maneuvering satellites

    Lace, Arthur A.

    In order to efficiently maintain space situational awareness, care must be taken to optimally allocate expensive observation resources. In most situations the available sensors capable of tracking spacecraft have their time split between many different monitoring responsibilities. Tracking maneuvering spacecraft can be especially difficult as the schedule of maneuvers may not be known and will often throw off previous orbital models. Effectively solving this tasking problem is an ongoing focus of research in the area of space situational awareness. Most methods of automated tasking do not make use of interacting multiple model extended Kalman filter techniques to better track satellites during maneuvers. This paper proposes a modification to a Fisher information gain and estimated state covariance based sensor tasking method to take maneuver probability and multiple model dynamics into account. By incorporating the probabilistic maneuvering model, sensor tasking can be improved during satellite maneuvers using constrained resources. The proposed methods are verified through the use of numerical simulations with multiple maneuvering satellites and both orbital and ground-based sensors.

  9. Locations of serial reach targets are coded in multiple reference frames.

    Thompson, Aidan A; Henriques, Denise Y P

    2010-12-01

    an egocentric frame anchored to the eye. However, the amount of change in this distance was smaller than predicted by a pure eye-fixed representation, suggesting that relative positions of the targets or allocentric coding was also used in sequential reach planning. The spatial coding and updating of sequential reach target locations seems to rely on a combined weighting of multiple reference frames, with one of them centered on the eye. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo

    Mukadder Korkmaz

    Full Text Available ABSTRACT INTRODUCTION: Benign paroxysmal positional vertigo (BPPV is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. OBJECTIVE: The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning procedures for treatment. METHODS: Data were obtained from the clinical records of 153 patients diagnosed with benign paroxysmal positional vertigo. Patients were treated by repositioning maneuvers. Demographic data and the factors including age, sex, canal type, duration of symptoms, comorbidities and number of repositioning maneuvers for relief were documented for statistical analysis. RESULTS: Age, sex, canal type and the duration of symptoms had no impact on the number of maneuvers. The most common comorbidity was spine problems. Hypertension was the only comorbidity that significantly associated with increased number of maneuvers. CONCLUSION: The presence of hypertension is a risk factor for repeated maneuvers in benign paroxysmal positional vertigo treatment. Physicians should be aware of the increased probability of repeated repositioning maneuvers in these group of patients. The role of comorbidities and vascular factors need to be further clarified in the course of benign paroxysmal positional vertigo.

  11. Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo.

    Korkmaz, Mukadder; Korkmaz, Hakan

    2016-01-01

    Benign paroxysmal positional vertigo (BPPV) is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning procedures for treatment. Data were obtained from the clinical records of 153 patients diagnosed with benign paroxysmal positional vertigo. Patients were treated by repositioning maneuvers. Demographic data and the factors including age, sex, canal type, duration of symptoms, comorbidities and number of repositioning maneuvers for relief were documented for statistical analysis. Age, sex, canal type and the duration of symptoms had no impact on the number of maneuvers. The most common comorbidity was spine problems. Hypertension was the only comorbidity that significantly associated with increased number of maneuvers. The presence of hypertension is a risk factor for repeated maneuvers in benign paroxysmal positional vertigo treatment. Physicians should be aware of the increased probability of repeated repositioning maneuvers in these group of patients. The role of comorbidities and vascular factors need to be further clarified in the course of benign paroxysmal positional vertigo. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. A Single Unexpected Change in Target- but Not Distractor Motion Impairs Multiple Object Tracking

    Hauke S. Meyerhoff

    2013-02-01

    Full Text Available Recent research addresses the question whether motion information of multiple objects contributes to maintaining a selection of objects across a period of motion. Here, we investigate whether target and/or distractor motion information is used during attentive tracking. We asked participants to track four objects and changed either the motion direction of targets, the motion direction of distractors, neither, or both during a brief flash in the middle of a tracking interval. We observed that a single direction change of targets is sufficient to impair tracking performance. In contrast, changing the motion direction of distractors had no effect on performance. This indicates that target- but not distractor motion information is evaluated during tracking.

  13. Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

    Machutta, Carl A.; Kollmann, Christopher S.; Lind, Kenneth E.; Bai, Xiaopeng; Chan, Pan F.; Huang, Jianzhong; Ballell, Lluis; Belyanskaya, Svetlana; Besra, Gurdyal S.; Barros-Aguirre, David; Bates, Robert H.; Centrella, Paolo A.; Chang, Sandy S.; Chai, Jing; Choudhry, Anthony E.; Coffin, Aaron; Davie, Christopher P.; Deng, Hongfeng; Deng, Jianghe; Ding, Yun; Dodson, Jason W.; Fosbenner, David T.; Gao, Enoch N.; Graham, Taylor L.; Graybill, Todd L.; Ingraham, Karen; Johnson, Walter P.; King, Bryan W.; Kwiatkowski, Christopher R.; Lelièvre, Joël; Li, Yue; Liu, Xiaorong; Lu, Quinn; Lehr, Ruth; Mendoza-Losana, Alfonso; Martin, John; McCloskey, Lynn; McCormick, Patti; O'Keefe, Heather P.; O'Keeffe, Thomas; Pao, Christina; Phelps, Christopher B.; Qi, Hongwei; Rafferty, Keith; Scavello, Genaro S.; Steiginga, Matt S.; Sundersingh, Flora S.; Sweitzer, Sharon M.; Szewczuk, Lawrence M.; Taylor, Amy; Toh, May Fern; Wang, Juan; Wang, Minghui; Wilkins, Devan J.; Xia, Bing; Yao, Gang; Zhang, Jean; Zhou, Jingye; Donahue, Christine P.; Messer, Jeffrey A.; Holmes, David; Arico-Muendel, Christopher C.; Pope, Andrew J.; Gross, Jeffrey W.; Evindar, Ghotas

    2017-07-01

    The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.

  14. Tracking and Recognition of Multiple Human Targets Moving in a Wireless Pyroelectric Infrared Sensor Network

    Ji Xiong

    2014-04-01

    Full Text Available With characteristics of low-cost and easy deployment, the distributed wireless pyroelectric infrared sensor network has attracted extensive interest, which aims to make it an alternate infrared video sensor in thermal biometric applications for tracking and identifying human targets. In these applications, effectively processing signals collected from sensors and extracting the features of different human targets has become crucial. This paper proposes the application of empirical mode decomposition and the Hilbert-Huang transform to extract features of moving human targets both in the time domain and the frequency domain. Moreover, the support vector machine is selected as the classifier. The experimental results demonstrate that by using this method the identification rates of multiple moving human targets are around 90%.

  15. First passage times for multiple particles with reversible target-binding kinetics

    Grebenkov, Denis S.

    2017-10-01

    We investigate the first passage problem for multiple particles that diffuse towards a target, partially adsorb there, and then desorb after a finite exponentially distributed residence time. We search for the first time when m particles undergoing such reversible target-binding kinetics are found simultaneously on the target that may trigger an irreversible chemical reaction or a biophysical event. Even if the particles are independent, the finite residence time on the target yields an intricate temporal coupling between particles. We compute analytically the mean first passage time (MFPT) for two independent particles by mapping the original problem to higher-dimensional surface-mediated diffusion and solving the coupled partial differential equations. The respective effects of the adsorption and desorption rates on the MFPT are revealed and discussed.

  16. NEWTONIAN IMPERIALIST COMPETITVE APPROACH TO OPTIMIZING OBSERVATION OF MULTIPLE TARGET POINTS IN MULTISENSOR SURVEILLANCE SYSTEMS

    A. Afghan-Toloee

    2013-09-01

    Full Text Available The problem of specifying the minimum number of sensors to deploy in a certain area to face multiple targets has been generally studied in the literatures. In this paper, we are arguing the multi-sensors deployment problem (MDP. The Multi-sensor placement problem can be clarified as minimizing the cost required to cover the multi target points in the area. We propose a more feasible method for the multi-sensor placement problem. Our method makes provision the high coverage of grid based placements while minimizing the cost as discovered in perimeter placement techniques. The NICA algorithm as improved ICA (Imperialist Competitive Algorithm is used to decrease the performance time to explore an enough solution compared to other meta-heuristic schemes such as GA, PSO and ICA. A three dimensional area is used for clarify the multiple target and placement points, making provision x, y, and z computations in the observation algorithm. A structure of model for the multi-sensor placement problem is proposed: The problem is constructed as an optimization problem with the objective to minimize the cost while covering all multiple target points upon a given probability of observation tolerance.

  17. Multi-target detection and positioning in crowds using multiple camera surveillance

    Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

    2018-04-01

    In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

  18. Detection-Discrimination Method for Multiple Repeater False Targets Based on Radar Polarization Echoes

    Z. W. ZONG

    2014-04-01

    Full Text Available Multiple repeat false targets (RFTs, created by the digital radio frequency memory (DRFM system of jammer, are widely used in practical to effectively exhaust the limited tracking and discrimination resource of defence radar. In this paper, common characteristic of radar polarization echoes of multiple RFTs is used for target recognition. Based on the echoes from two receiving polarization channels, the instantaneous polarization radio (IPR is defined and its variance is derived by employing Taylor series expansion. A detection-discrimination method is designed based on probability grids. By using the data from microwave anechoic chamber, the detection threshold of the method is confirmed. Theoretical analysis and simulations indicate that the method is valid and feasible. Furthermore, the estimation performance of IPRs of RFTs due to the influence of signal noise ratio (SNR is also covered.

  19. Exploitation of Microdoppler and Multiple Scattering Phenomena for Radar Target Recognition

    2006-08-24

    progress on the reserach grant "Exploitation of MicroDoppler and Multiple Scattering Phenomena for Radar Target Recognition" during the period 1...paper describes a methodology of modeling A number of ray-based EM techniques have been interferometric synthetic aperture radar (IFSAR) images...modes including the single present an IFSAR simulation methodology to simulate the antenna transmit mode, the ping-pong mode or the repeat interferogram

  20. One Novel Multiple-Target Plasmid Reference Molecule Targeting Eight Genetically Modified Canola Events for Genetically Modified Canola Detection.

    Li, Zhuqing; Li, Xiang; Wang, Canhua; Song, Guiwen; Pi, Liqun; Zheng, Lan; Zhang, Dabing; Yang, Litao

    2017-09-27

    Multiple-target plasmid DNA reference materials have been generated and utilized as good substitutes of matrix-based reference materials in the analysis of genetically modified organisms (GMOs). Herein, we report the construction of one multiple-target plasmid reference molecule, pCAN, which harbors eight GM canola event-specific sequences (RF1, RF2, MS1, MS8, Topas 19/2, Oxy235, RT73, and T45) and a partial sequence of the canola endogenous reference gene PEP. The applicability of this plasmid reference material in qualitative and quantitative PCR assays of the eight GM canola events was evaluated, including the analysis of specificity, limit of detection (LOD), limit of quantification (LOQ), and performance of pCAN in the analysis of various canola samples, etc. The LODs are 15 copies for RF2, MS1, and RT73 assays using pCAN as the calibrator and 10 genome copies for the other events. The LOQ in each event-specific real-time PCR assay is 20 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and PEP assays are between 91% and 97%, and the squared regression coefficients (R 2 ) are all higher than 0.99. The quantification bias values varied from 0.47% to 20.68% with relative standard deviation (RSD) from 1.06% to 24.61% in the quantification of simulated samples. Furthermore, 10 practical canola samples sampled from imported shipments in the port of Shanghai, China, were analyzed employing pCAN as the calibrator, and the results were comparable with those assays using commercial certified materials as the calibrator. Concluding from these results, we believe that this newly developed pCAN plasmid is one good candidate for being a plasmid DNA reference material in the detection and quantification of the eight GM canola events in routine analysis.

  1. Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens

    Mauricio Lopez-Obando

    2016-11-01

    Full Text Available Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants.

  2. EBF factors drive expression of multiple classes of target genes governing neuronal development.

    Green, Yangsook S; Vetter, Monica L

    2011-04-30

    Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

  3. EBF factors drive expression of multiple classes of target genes governing neuronal development

    Vetter Monica L

    2011-04-01

    Full Text Available Abstract Background Early B cell factor (EBF family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. Results We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. Conclusions The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

  4. Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions

    Calvo-Ortega, J.F., E-mail: jfcdrr@yahoo.es; Pozo, M.; Moragues, S.; Casals, J.

    2017-07-01

    To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom on the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application ( (www.radiochromic.com)) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm{sup 2} region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed.

  5. Low power multiple shell fusion targets for use with electron and ion beams

    Lindl, J.D.; Bangerter, R.O.

    1975-01-01

    Use of double shell targets with a separate low Z, low density ablator at large radius for the outer shell, reduces the focusing and power requirements while maintaining reasonable aspect ratios. A high Z, high density pusher shell is placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. Ion beams appear to be a promising power source and breakeven at 10-20 Terrawatts with 10 MeV alpha particles appears feasible. Predicted performance of targets with various energy sources is shown and comparison is made with single shell targets

  6. Concurrent image-based visual servoing with adaptive zooming for non-cooperative rendezvous maneuvers

    Pomares, Jorge; Felicetti, Leonard; Pérez, Javier; Emami, M. Reza

    2018-02-01

    An image-based servo controller for the guidance of a spacecraft during non-cooperative rendezvous is presented in this paper. The controller directly utilizes the visual features from image frames of a target spacecraft for computing both attitude and orbital maneuvers concurrently. The utilization of adaptive optics, such as zooming cameras, is also addressed through developing an invariant-image servo controller. The controller allows for performing rendezvous maneuvers independently from the adjustments of the camera focal length, improving the performance and versatility of maneuvers. The stability of the proposed control scheme is proven analytically in the invariant space, and its viability is explored through numerical simulations.

  7. Cassini-Huygens maneuver automation for navigation

    Goodson, Troy; Attiyah, Amy; Buffington, Brent; Hahn, Yungsun; Pojman, Joan; Stavert, Bob; Strange, Nathan; Stumpf, Paul; Wagner, Sean; Wolff, Peter; hide

    2006-01-01

    Many times during the Cassini-Huygens mission to Saturn, propulsive maneuvers must be spaced so closely together that there isn't enough time or workforce to execute the maneuver-related software manually, one subsystem at a time. Automation is required. Automating the maneuver design process has involved close cooperation between teams. We present the contribution from the Navigation system. In scope, this includes trajectory propagation and search, generation of ephemerides, general tasks such as email notification and file transfer, and presentation materials. The software has been used to help understand maneuver optimization results, Huygens probe delivery statistics, and Saturn ring-plane crossing geometry. The Maneuver Automation Software (MAS), developed for the Cassini-Huygens program enables frequent maneuvers by handling mundane tasks such as creation of deliverable files, file delivery, generation and transmission of email announcements, generation of presentation material and other supporting documentation. By hand, these tasks took up hours, if not days, of work for each maneuver. Automated, these tasks may be completed in under an hour. During the cruise trajectory the spacing of maneuvers was such that development of a maneuver design could span about a month, involving several other processes in addition to that described, above. Often, about the last five days of this process covered the generation of a final design using an updated orbit-determination estimate. To support the tour trajectory, the orbit determination data cut-off of five days before the maneuver needed to be reduced to approximately one day and the whole maneuver development process needed to be reduced to less than a week..

  8. Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo

    Korkmaz, Mukadder; Korkmaz, Hakan

    2016-01-01

    ABSTRACT INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. OBJECTIVE: The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning proced...

  9. The pituitary tumor transforming gene 1 (PTTG-1: An immunological target for multiple myeloma

    Gagliano Nicoletta

    2008-04-01

    Full Text Available Abstract Background Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1 has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues. Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients. Methods We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue. Results We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA. Four of the 6 investigated cell lines (66.6% were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients. Conclusion We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.

  10. Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes

    Ferreira, Raphael; Gatto, Francesco; Nielsen, Jens

    2017-01-01

    Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple ge...

  11. Method for Multiple Targets Tracking in Cognitive Radar Based on Compressed Sensing

    Yang Jun

    2016-02-01

    Full Text Available A multiple targets cognitive radar tracking method based on Compressed Sensing (CS is proposed. In this method, the theory of CS is introduced to the case of cognitive radar tracking process in multiple targets scenario. The echo signal is sparsely expressed. The designs of sparse matrix and measurement matrix are accomplished by expressing the echo signal sparsely, and subsequently, the restruction of measurement signal under the down-sampling condition is realized. On the receiving end, after considering that the problems that traditional particle filter suffers from degeneracy, and require a large number of particles, the particle swarm optimization particle filter is used to track the targets. On the transmitting end, the Posterior Cramér-Rao Bounds (PCRB of the tracking accuracy is deduced, and the radar waveform parameters are further cognitively designed using PCRB. Simulation results show that the proposed method can not only reduce the data quantity, but also provide a better tracking performance compared with traditional method.

  12. 46 CFR 109.564 - Maneuvering characteristics.

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Maneuvering characteristics. 109.564 Section 109.564 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS OPERATIONS Miscellaneous § 109.564 Maneuvering characteristics. (a) The master or person in charge of each...

  13. Flight Test Maneuvers for Efficient Aerodynamic Modeling

    Morelli, Eugene A.

    2011-01-01

    Novel flight test maneuvers for efficient aerodynamic modeling were developed and demonstrated in flight. Orthogonal optimized multi-sine inputs were applied to aircraft control surfaces to excite aircraft dynamic response in all six degrees of freedom simultaneously while keeping the aircraft close to chosen reference flight conditions. Each maneuver was designed for a specific modeling task that cannot be adequately or efficiently accomplished using conventional flight test maneuvers. All of the new maneuvers were first described and explained, then demonstrated on a subscale jet transport aircraft in flight. Real-time and post-flight modeling results obtained using equation-error parameter estimation in the frequency domain were used to show the effectiveness and efficiency of the new maneuvers, as well as the quality of the aerodynamic models that can be identified from the resultant flight data.

  14. Experimental visualization of rapid maneuvering fish

    Daigh, S.; Techet, A. H.

    2003-11-01

    A freshwater tropical fish, Danio aequippinatus, is studied undergoing rapid turning and fast starting maneuvers. This agile species of fish is ideal for this study as it is capable of quick turning and darting motions up to 5g's. The fgish studied are 4-5 cm in length. The speed and kinematics of the maneuvering is determined by video analysis. Planar and stereo Particle Image Velocimetry (PIV) is used to map the vortical patterns in the wake of the maneuvering fish. PIV visualizations reveal that during C-shaped maneuvers a ring shaped jet vortex is formed. Fast starting behavior is also presented. PIV data is used to approixmate the thrust vectoring force produced during each maneuver.

  15. Two-dimensional multiplicity fluctuation analysis of target residues in nuclear collisions

    Dong-Hai, Zhang; Yao-Jie, Niu; Li-Chun, Wang; Wen-Jun, Yan; Li-Juan, Gao; Ming-Xing, Li; Li-Ping, Wu; Hui-Ling, Li; Jun-Sheng, Li

    2010-01-01

    Multiplicity fluctuation of the target residues emitted in the interactions in a wide range of projectile energies from 500 A MeV to 60 A GeV is investigated in the framework of two-dimensional scaled factorial moment methodology. The evidence of non-statistical multiplicity fluctuation is found in 16 O–AgBr collisions at 60 A GeV, but not in 56 Fe–AgBr collisions at 500 A MeV, 84 Kr–AgBr collisions at 1.7 A GeV, 16 O–AgBr collisions at 3.7 A GeV and 197 Au–AgBr collisions at 10.7 A GeV. (nuclear physics)

  16. Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target

    Adolph, C.

    2017-04-10

    Precise measurements of charged-kaon multiplicities in deep inelastic scattering were performed. The results are presented in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar 6 LiD target. They cover the kinematic domain 1 (GeV/c)2 5 GeV/c^2 in the invariant mass of the hadronic system. The results from the sum of the z-integrated K+ and K- multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.

  17. Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target

    C. Adolph

    2017-04-01

    Full Text Available Precise measurements of charged-kaon multiplicities in deep inelastic scattering were performed. The results are presented in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar 6LiD target. They cover the kinematic domain 1(GeV/c25 GeV/c2 in the invariant mass of the hadronic system. The results from the sum of the z-integrated K+ and K− multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.

  18. A Targeted "Capture" and "Removal" Scavenger toward Multiple Pollutants for Water Remediation based on Molecular Recognition.

    Wang, Jie; Shen, Haijing; Hu, Xiaoxia; Li, Yan; Li, Zhihao; Xu, Jinfan; Song, Xiufeng; Zeng, Haibo; Yuan, Quan

    2016-03-01

    For the water remediation techniques based on adsorption, the long-standing contradictories between selectivity and multiple adsorbability, as well as between affinity and recyclability, have put it on weak defense amid more and more severe environment crisis. Here, a pollutant-targeting hydrogel scavenger is reported for water remediation with both high selectivity and multiple adsorbability for several pollutants, and with strong affinity and good recyclability through rationally integrating the advantages of multiple functional materials. In the scavenger, aptamers fold into binding pockets to accommodate the molecular structure of pollutants to afford perfect selectivity, and Janus nanoparticles with antibacterial function as well as anisotropic surfaces to immobilize multiple aptamers allow for simultaneously handling different kinds of pollutants. The scavenger exhibits high efficiencies in removing pollutants from water and it can be easily recycled for many times without significant loss of loading capacities. Moreover, the residual concentrations of each contaminant are well below the drinking water standards. Thermodynamic behavior of the adsorption process is investigated and the rate-controlling process is determined. Furthermore, a point of use device is constructed and it displays high efficiency in removing pollutants from environmental water. The scavenger exhibits great promise to be applied in the next generation of water purification systems.

  19. Analysis of multiple-foil XRL targets using x-ray spectroscopy

    Wang, J.; Boehly, T.; Yaakobi, B.; Epstein, R.; Meyerhofer, D.; Richardson, M.C.; Russotto, M.; Soures, J.M.

    1989-01-01

    The multiple-foil collisional excitation x-ray laser targets proposed by LLE have been studied spectroscopically. Using spatially resolved 3d-2p x-ray spectra, the authors compare the temperatures and densities obtained in single- and double-foil geometries. They use the ratio of the dipole transitions to the electric quadrupole transitions in the Neon-like species as a density diagnostic. A non-LTE average-ion atomic physics model is used to describe the ionization process and a relativistic atomic physics code is used for calculation of the level energies, populations, and gain calculations. They support their claims that the double-vfoils provide higher densities and in some cases concave density profiles. The XUV spectra in the range of 20-300 A show the effect of target geometry and incident laser intensity on the lasing lines and the ionization balance

  20. One For All? Hitting multiple Alzheimer’s Disease targets with one drug

    Rebecca Ellen Hughes

    2016-04-01

    Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  1. Interpolating between random walks and optimal transportation routes: Flow with multiple sources and targets

    Guex, Guillaume

    2016-05-01

    In recent articles about graphs, different models proposed a formalism to find a type of path between two nodes, the source and the target, at crossroads between the shortest-path and the random-walk path. These models include a freely adjustable parameter, allowing to tune the behavior of the path toward randomized movements or direct routes. This article presents a natural generalization of these models, namely a model with multiple sources and targets. In this context, source nodes can be viewed as locations with a supply of a certain good (e.g. people, money, information) and target nodes as locations with a demand of the same good. An algorithm is constructed to display the flow of goods in the network between sources and targets. With again a freely adjustable parameter, this flow can be tuned to follow routes of minimum cost, thus displaying the flow in the context of the optimal transportation problem or, by contrast, a random flow, known to be similar to the electrical current flow if the random-walk is reversible. Moreover, a source-targetcoupling can be retrieved from this flow, offering an optimal assignment to the transportation problem. This algorithm is described in the first part of this article and then illustrated with case studies.

  2. SAR Target Recognition Based on Multi-feature Multiple Representation Classifier Fusion

    Zhang Xinzheng

    2017-10-01

    Full Text Available In this paper, we present a Synthetic Aperture Radar (SAR image target recognition algorithm based on multi-feature multiple representation learning classifier fusion. First, it extracts three features from the SAR images, namely principal component analysis, wavelet transform, and Two-Dimensional Slice Zernike Moments (2DSZM features. Second, we harness the sparse representation classifier and the cooperative representation classifier with the above-mentioned features to get six predictive labels. Finally, we adopt classifier fusion to obtain the final recognition decision. We researched three different classifier fusion algorithms in our experiments, and the results demonstrate thatusing Bayesian decision fusion gives thebest recognition performance. The method based on multi-feature multiple representation learning classifier fusion integrates the discrimination of multi-features and combines the sparse and cooperative representation classification performance to gain complementary advantages and to improve recognition accuracy. The experiments are based on the Moving and Stationary Target Acquisition and Recognition (MSTAR database,and they demonstrate the effectiveness of the proposed approach.

  3. Multiple targets of salicylic acid and its derivatives in plants and animals

    Daniel F. Klessig

    2016-05-01

    Full Text Available Salicylic acid (SA is a critical plant hormone that is involved in many processes, including seed germination, root initiation, stomatal closure, floral induction, thermogenesis, and response to abiotic and biotic stresses. Its central role in plant immunity, although extensively studied, is still only partially understood. Classical biochemical approaches and, more recently, genome-wide high-throughput screens have identified more than two dozen plant SA-binding proteins (SABPs, as well as multiple candidates that have yet to be characterized. Some of these proteins bind SA with high affinity, while the affinity others exhibit is low. Given that SA levels vary greatly even within a particular plant species depending on subcellular location, tissue type, developmental stage, and with respect to both time and location after an environmental stimulus such as infection, the presence of SABPs exhibiting a wide range of affinities for SA may provide great flexibility and multiple mechanisms through which SA can act. SA and its derivatives, both natural and synthetic, also have multiple targets in animals/humans. Interestingly, many of these proteins, like their plant counterparts, are associated with immunity or disease development. Two recently identified SABPs, High Mobility Group Box protein (HMGB and Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH, are critical proteins that not only serve key structural or metabolic functions, but also play prominent roles in disease responses in both kingdoms.

  4. Multiple cyber attacks against a target with observation errors and dependent outcomes: Characterization and optimization

    Hu, Xiaoxiao; Xu, Maochao; Xu, Shouhuai; Zhao, Peng

    2017-01-01

    In this paper we investigate a cybersecurity model: An attacker can launch multiple attacks against a target with a termination strategy that says that the attacker will stop after observing a number of successful attacks or when the attacker is out of attack resources. However, the attacker's observation of the attack outcomes (i.e., random variables indicating whether the target is compromised or not) has an observation error that is specified by both a false-negative and a false-positive probability. The novelty of the model we study is the accommodation of the dependence between the attack outcomes, because the dependence was assumed away in the literature. In this model, we characterize the monotonicity and bounds of the compromise probability (i.e., the probability that the target is compromised). In addition to extensively showing the impact of dependence on quantities such as compromise probability and attack cost, we give methods for finding the optimal strategy that leads to maximum compromise probability or minimum attack cost. This study highlights that the dependence between random variables cannot be assumed away, because the results will be misleading. - Highlights: • A novel cybersecurity model is proposed to accommodate the dependence among attack outcomes. • The monotonicity and bounds of the compromise probability are studied. • The dependence effect on the compromise probability and attack cost is discussed via simulation. • The optimal strategy that leads to maximum compromise probability or minimum attack cost is presented.

  5. Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.

    Tagde, Ashujit; Markert, Tahireh; Rajabi, Hasan; Hiraki, Masayuki; Alam, Maroof; Bouillez, Audrey; Avigan, David; Anderson, Kenneth; Kufe, Donald

    2017-09-19

    The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM . These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.

  6. Sensitivity studies of the neutron multiplicity spectrum in the spallation of Pb targets

    Sinha, A.; Garg, S.B.; Srinivasan, M.

    1986-01-01

    The number of neutrons produced per incident proton in the spallation of Pb targets is of direct relevance to the design of accelerator breeders. The nuclear cascade initiated by high-energy protons in spallation targets is usually described by an intranuclear cascade evaporation (INCE) model. Even though this model describes various average nuclear properties of spallation targets fairly well, differential quantities such as energy spectra, angular spectra etc., are not reproduced within the limits of experimental uncertainty. One of the reasons for this is the uncertainty in the magnitude of the parameters involved in the model, notably the level density parameter Bsub(O) whose magnitude is quoted by different workers to be in the range of 8-20 MeV. The accuracy of Bsub(O) could be improved if we could experimentally determine a quantity which is much more sensitive to Bsub(O) than the average neutron yield. In this paper we discuss one such quantity, namely the neutron multiplicity spectrum (MS). We compute the MS due to the spallation of Pb targets of different sizes at proton energies of 1.5, 1.0 and 0.59 GeV using the Monte Carlo code HETC. It is noticed that for the 1.5 GeV proton case the probability P(ν) for leakage of ν neutrons for ν in the range of 60-65, changes by about 70% when Bsub(O) is varied from 8 to 20 MeV. The corresponding change in the average neutron yield is <20%. It is therefore suggested that an accurate measurement of the MS can serve as a useful tool to narrow down the range of uncertainty in the Bsub(O) parameter. (author)

  7. P2-21: Searching for Multiple Targets Using the iPad

    Ian Thornton

    2012-10-01

    Full Text Available Search for multiple targets is constrained by both retrospective (i.e., where you've been and prospective (i.e., where you're planning to go components of performance. Previous studies using the Multi-Item Localisation (MILO task have demonstrated that participants accurately remember and discount locations they have already visited and that they plan future actions up to 2 or 3 items ahead (Thornton & Horowitz, 2004 Perception & Psychophysics 66 38–50. A prominent feature of the MILO serial-reaction time (SRT function is a highly elevated, that is slowed, response, to T1 compared to T2 and all the other items. This “prospective gap” is typically between 600 ms and 1000 ms. Here we present three experiments that use the MILO iPad app to explore this “prospective gap”. In Experiment 1, we “shuffled” the position of future targets each time a response was made. This blocks planning and thus slows all responses to the level of first target, effectively eliminating the gap. In Experiment 2, participants responded to eight identical targets, removing the need to plan a specific sequence of actions. In this situation, absolute response time is greatly reduced and the T1–T2 gap shrinks to around 350 ms. In Experiment 3, participants repeated their search through the same array 10 times. Under these circumstances, the gap systematically reduced from 1300 ms on trial 1 to 300 ms on trial 10. Together, these results suggest that the previously observed prospective gap is a combination of set-up time for registering a new visual layout, response preparation, and sequence planning.

  8. Canadarm2 Maneuvers Quest Airlock

    2001-01-01

    At the control of Expedition Two Flight Engineer Susan B. Helms, the newly-installed Canadian-built Canadarm2, Space Station Remote Manipulator System (SSRMS) maneuvers the Quest Airlock into the proper position to be mated onto the starboard side of the Unity Node I during the first of three extravehicular activities (EVA) of the STS-104 mission. The Quest Airlock makes it easier to perform space walks, and allows both Russian and American spacesuits to be worn when the Shuttle is not docked with the International Space Station (ISS). American suits will not fit through Russion airlocks at the Station. The Boeing Company, the space station prime contractor, built the 6.5-ton (5.8 metric ton) airlock and several other key components at the Marshall Space Flight Center (MSFC), in the same building where the Saturn V rocket was built. Installation activities were supported by the development team from the Payload Operations Control Center (POCC) located at the MSFC and the Mission Control Center at NASA's Johnson Space Flight Center in Houston, Texas.

  9. Automated Robust Maneuver Design and Optimization

    National Aeronautics and Space Administration — NASA is seeking improvements to the current technologies related to Position, Navigation and Timing. In particular, it is desired to automate precise maneuver...

  10. Review about hiperventilation test and Valsalva Maneuver

    Eduardo Antonio MENA-DOMÍNGUEZ

    2018-04-01

    Full Text Available Introduction and objective: With this paper, we pretend to explain the characteristics and the field of application of two clinical explorations used in the patient with suspected vestibular pathology, the hyperventilation maneuver and the Valsalva maneuver. Methodology: Narrative review. Results: Through different neurophysiological mechanisms, hyperventilation can induce nystagmus in cases of vestibular asymmetry, both peripheral and central. The Valsalva maneuver may also trigger nystagmus and vertigo because of direct transmission of internal ear pressure in cases of perilymphatic fistula, anomalies of the cranio-cervical junction (Arnold-Chiari malformation, and other ossicles, oval window and saccule pathologies. Discussion and conclusions: Both the hyperventilation test and the Valsalva maneuver should be included in the battery of tests for patients with vestibular pathology to, depending on the results obtained, anatomically locate the site of the lesion and justify the use of imaging techniques.

  11. Simultaneous detection of multiple DNA targets by integrating dual-color graphene quantum dot nanoprobes and carbon nanotubes.

    Qian, Zhaosheng; Shan, Xiaoyue; Chai, Lujing; Chen, Jianrong; Feng, Hui

    2014-12-01

    Simultaneous detection of multiple DNA targets was achieved based on a biocompatible graphene quantum dots (GQDs) and carbon nanotubes (CNTs) platform through spontaneous assembly between dual-color GQD-based probes and CNTs and subsequently self-recognition between DNA probes and targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. New and emerging immune-targeted drugs for the treatment of multiple sclerosis.

    Palmer, Alan M

    2014-07-01

    Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.

  13. 14 CFR 27.337 - Limit maneuvering load factor.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Limit maneuvering load factor. 27.337... Limit maneuvering load factor. The rotorcraft must be designed for— (a) A limit maneuvering load factor... load factor not less than 2.0 and any negative limit maneuvering load factor of not less than −0.5 for...

  14. 14 CFR 29.337 - Limit maneuvering load factor.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Limit maneuvering load factor. 29.337... Limit maneuvering load factor. The rotorcraft must be designed for— (a) A limit maneuvering load factor... load factor not less than 2.0 and any negative limit maneuvering load factor of not less than −0.5 for...

  15. Optimal Autonomous Spacecraft Resiliency Maneuvers Using Metaheuristics

    2014-09-15

    This work was accepted for published by the American Institute of Aeronautics and Astronautics (AIAA) Journal of Spacecraft and Rockets in July 2014...publication in the AIAA Journal of Spacecraft and Rockets . Chapter 5 introduces an impulsive maneuvering strategy to deliver a spacecraft to its final...upon arrival r2 and v2 , respectively. The variable T2 determines the time of flight needed to make the maneuver, and the variable θ2 determines the

  16. A novel sampling method for multiple multiscale targets from scattering amplitudes at a fixed frequency

    Liu, Xiaodong

    2017-08-01

    A sampling method by using scattering amplitude is proposed for shape and location reconstruction in inverse acoustic scattering problems. Only matrix multiplication is involved in the computation, thus the novel sampling method is very easy and simple to implement. With the help of the factorization of the far field operator, we establish an inf-criterion for characterization of underlying scatterers. This result is then used to give a lower bound of the proposed indicator functional for sampling points inside the scatterers. While for the sampling points outside the scatterers, we show that the indicator functional decays like the bessel functions as the sampling point goes away from the boundary of the scatterers. We also show that the proposed indicator functional continuously depends on the scattering amplitude, this further implies that the novel sampling method is extremely stable with respect to errors in the data. Different to the classical sampling method such as the linear sampling method or the factorization method, from the numerical point of view, the novel indicator takes its maximum near the boundary of the underlying target and decays like the bessel functions as the sampling points go away from the boundary. The numerical simulations also show that the proposed sampling method can deal with multiple multiscale case, even the different components are close to each other.

  17. M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis.

    He Zhou

    Full Text Available Heparan sulfate proteoglycans (HSPGs play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.

  18. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    Hengeveld, P J; Kersten, M J

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916)

  19. Nucleotide excision repair is a potential therapeutic target in multiple myeloma

    Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

    2018-01-01

    Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

  20. Hairpin RNA Targeting Multiple Viral Genes Confers Strong Resistance to Rice Black-Streaked Dwarf Virus

    Fangquan Wang

    2016-05-01

    Full Text Available Rice black-streaked dwarf virus (RBSDV belongs to the genus Fijivirus in the family of Reoviridae and causes severe yield loss in rice-producing areas in Asia. RNA silencing, as a natural defence mechanism against plant viruses, has been successfully exploited for engineering virus resistance in plants, including rice. In this study, we generated transgenic rice lines harbouring a hairpin RNA (hpRNA construct targeting four RBSDV genes, S1, S2, S6 and S10, encoding the RNA-dependent RNA polymerase, the putative core protein, the RNA silencing suppressor and the outer capsid protein, respectively. Both field nursery and artificial inoculation assays of three generations of the transgenic lines showed that they had strong resistance to RBSDV infection. The RBSDV resistance in the segregating transgenic populations correlated perfectly with the presence of the hpRNA transgene. Furthermore, the hpRNA transgene was expressed in the highly resistant transgenic lines, giving rise to abundant levels of 21–24 nt small interfering RNA (siRNA. By small RNA deep sequencing, the RBSDV-resistant transgenic lines detected siRNAs from all four viral gene sequences in the hpRNA transgene, indicating that the whole chimeric fusion sequence can be efficiently processed by Dicer into siRNAs. Taken together, our results suggest that long hpRNA targeting multiple viral genes can be used to generate stable and durable virus resistance in rice, as well as other plant species.

  1. Hairpin RNA Targeting Multiple Viral Genes Confers Strong Resistance to Rice Black-Streaked Dwarf Virus.

    Wang, Fangquan; Li, Wenqi; Zhu, Jinyan; Fan, Fangjun; Wang, Jun; Zhong, Weigong; Wang, Ming-Bo; Liu, Qing; Zhu, Qian-Hao; Zhou, Tong; Lan, Ying; Zhou, Yijun; Yang, Jie

    2016-05-11

    Rice black-streaked dwarf virus (RBSDV) belongs to the genus Fijivirus in the family of Reoviridae and causes severe yield loss in rice-producing areas in Asia. RNA silencing, as a natural defence mechanism against plant viruses, has been successfully exploited for engineering virus resistance in plants, including rice. In this study, we generated transgenic rice lines harbouring a hairpin RNA (hpRNA) construct targeting four RBSDV genes, S1, S2, S6 and S10, encoding the RNA-dependent RNA polymerase, the putative core protein, the RNA silencing suppressor and the outer capsid protein, respectively. Both field nursery and artificial inoculation assays of three generations of the transgenic lines showed that they had strong resistance to RBSDV infection. The RBSDV resistance in the segregating transgenic populations correlated perfectly with the presence of the hpRNA transgene. Furthermore, the hpRNA transgene was expressed in the highly resistant transgenic lines, giving rise to abundant levels of 21-24 nt small interfering RNA (siRNA). By small RNA deep sequencing, the RBSDV-resistant transgenic lines detected siRNAs from all four viral gene sequences in the hpRNA transgene, indicating that the whole chimeric fusion sequence can be efficiently processed by Dicer into siRNAs. Taken together, our results suggest that long hpRNA targeting multiple viral genes can be used to generate stable and durable virus resistance in rice, as well as other plant species.

  2. Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes.

    Chang, Hsin-Fang; Bzeih, Hawraa; Schirra, Claudia; Chitirala, Praneeth; Halimani, Mahantappa; Cordat, Emmanuelle; Krause, Elmar; Rettig, Jens; Pattu, Varsha

    2016-09-15

    CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process. Copyright © 2016 by The American Association of Immunologists, Inc.

  3. Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

    Bosseboeuf, Adrien; Feron, Delphine; Tallet, Anne; Rossi, Cédric; Charlier, Cathy; Garderet, Laurent; Caillot, Denis; Moreau, Philippe; Cardó-Vila, Marina; Pasqualini, Renata; Nelson, Alfreda Destea; Wilson, Bridget S.; Perreault, Hélène; Piver, Eric; Weigel, Pierre; Harb, Jean; Bigot-Corbel, Edith; Hermouet, Sylvie

    2017-01-01

    Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1–specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection–linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients. PMID:28978808

  4. Damage to Preheated Tungsten Targets after Multiple Plasma Impacts Simulating ITER ELMs

    Garkusha, I.E.; Bandura, A.N.; Byrka, O.V.; Chebotarev, V.V.; Makhlay, V.A.; Tereshin, V.I. [Kharkov Inst. of Physics and Technology, Inst. of Plasma Physics of National Science Center, Akademicheskaya street, 1, 61108 Kharkov (Ukraine); Landman, I.; Pestchanyi, S. [FZK-Forschungszentrum Karlsruhe, Association Euratom-FZK, Technik und Umwelt, Postfach 3640, D-7602 1 Karlsruhe (Germany)

    2007-07-01

    Full text of publication follows: The energy loads onto ITER divertor surfaces associated with the Type I ELMs are expected to be up to 1 MJ/m{sup 2} during 0.1-0.5 ms, with the number of pulses about 103 per discharge. Tungsten is a candidate material for major part of the surface, but its brittleness can result in substantial macroscopic erosion after the repetitive heat loads. To minimize the brittle destruction, tungsten may be preheated above the ductile-to-brittle transition temperature. In this work the behavior of preheated tungsten targets under repetitive ELM-like plasma pulses is studied in simulation experiments with the quasi-stationary plasma accelerator QSPA Kh-50. The targets have been exposed up to 450 pulses of the duration 0.25 ms and the heat loads either 0.45 MJ/m{sup 2} or 0.75 MJ/m{sup 2}, which is respectively below and above the melting threshold. During the exposures the targets were permanently kept preheated at 650 deg. C by a heater at target backside. In the course of exposures the irradiated surfaces were examined after regular numbers of pulses using the SEM and the optical microscopy. The profilometry, XRD, microhardness and weight loss measurements have been performed, as well as comparisons of surface damages after the heat loads both below and above the melting threshold. It is obtained that macro-cracks do not develop on the preheated surface. After the impacts with surface melting, a fine mesh of intergranular microcracks has appeared. The width of fine intergranular cracks grows with pulse number, achieving 1-1.5 microns after 100 pulses, and after 210 pulses the crack width increases up to 20 microns, which is comparable with grain sizes. Threshold changes in surface morphology resulting in corrugation structures and pits on the surface as well as importance of surface tension in resulted 'micro-brush' structures are discussed. Further evolution of the surface pattern is caused by loss of separated grains on exposed

  5. Detecting and Georegistering Moving Ground Targets in Airborne QuickSAR via Keystoning and Multiple-Phase Center Interferometry

    R. P. Perry

    2008-03-01

    Full Text Available SAR images experience significant range walk and, without some form of motion compensation, can be quite blurred. The MITRE-developed Keystone formatting simultaneously and automatically compensates for range walk due to the radial velocity component of each moving target, independent of the number of targets or the value of each target's radial velocity with respect to the ground. Target radial motion also causes moving targets in synthetic aperture radar images to appear at locations offset from their true instantaneous locations on the ground. In a multichannel radar, the interferometric phase values associated with all nonmoving points on the ground appear as a continuum of phase differences while the moving targets appear as interferometric phase discontinuities. By multiple threshold comparisons and grouping of pixels within the intensity and the phase images, we show that it is possible to reliably detect and accurately georegister moving targets within short-duration SAR (QuickSAR images.

  6. Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO Radar Based on the Elements of the Covariance Matrix

    Zhengyan Zhang

    2018-03-01

    Full Text Available In this paper, we consider the problem of tracking the direction of arrivals (DOA and the direction of departure (DOD of multiple targets for bistatic multiple-input multiple-output (MIMO radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

  7. Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO) Radar Based on the Elements of the Covariance Matrix.

    Zhang, Zhengyan; Zhang, Jianyun; Zhou, Qingsong; Li, Xiaobo

    2018-03-07

    In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

  8. Penalty dynamic programming algorithm for dim targets detection in sensor systems.

    Huang, Dayu; Xue, Anke; Guo, Yunfei

    2012-01-01

    In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

  9. Targeting p110gamma in gastrointestinal cancers: attack on multiple fronts

    Marco eFalasca

    2014-10-01

    Full Text Available Phosphoinositide 3-kinases (PI3Ks regulate several cellular functions that are critical for cancer progression and development, including cell survival, proliferation and migration. Three classes of PI3Ks exist with the class I PI3K encompassing four isoforms of the catalytic subunit known as p110α, p110β, p110γ and p110δ. Although for many years attention has been mainly focused on p110α recent evidence supports the conclusion that p110β, p110γ and p110δ can also have a role in cancer. Amongst these, accumulating evidence now supports the conclusion that p110γ is involved in several cellular processes associated with cancer development and progression and indeed this specific isoform has emerged as a novel important player in cancer progression. Studies from our laboratory have identified a specific overexpression of p110γ in human pancreatic ductal adenocarcinoma (PDAC and in hepatocellular carcinoma (HCC tissues compared to their normal counterparts. Our data have further established that selective inhibition of this PI3K isoform is able to block PDAC and HCC cell proliferation, strongly suggesting that pharmacological inhibition of this enzyme can directly affect these tumors growth. Furthermore increasing evidence suggests that p110γ plays also a key role in the interactions between cancer cells and tumor microenvironment and in particular in tumor-associated immune response. It has also been reported that p110γ can regulate invasion of myeloid cells into tumors and tumor angiogenesis. Finally p110γ has also been directly involved in regulation of cancer cell migration. Taken together these data indicate that p110γ plays multiple roles in regulation of several processes that are critical for tumor progression and metastasis. This review will discuss the role of p110γ in gastrointestinal tumor development and progression and how targeting this enzyme might represent a way to target very aggressive tumors such as pancreatic and

  10. Propulsive Maneuver Design for the 2007 Mars Phoenix Lander Mission

    Raofi, Behzad; Bhat, Ramachandra S.; Helfrich, Cliff

    2008-01-01

    On May 25, 2008, the Mars Phoenix Lander (PHX) successfully landed in the northern planes of Mars in order to continue and complement NASA's "follow the water" theme as its predecessor Mars missions, such as Mars Odyssey (ODY) and Mars Exploration Rovers, have done in recent years. Instruments on the lander, through a robotic arm able to deliver soil samples to the deck, will perform in-situ and remote-sensing investigations to characterize the chemistry of materials at the local surface, subsurface, and atmosphere. Lander instruments will also identify the potential history of key indicator elements of significance to the biological potential of Mars, including potential organics within any accessible water ice. Precise trajectory control and targeting were necessary in order to achieve the accurate atmospheric entry conditions required for arriving at the desired landing site. The challenge for the trajectory control maneuver design was to meet or exceed these requirements in the presence of spacecraft limitations as well as other mission constraints. This paper describes the strategies used, including the specialized targeting specifically developed for PHX, in order to design and successfully execute the propulsive maneuvers that delivered the spacecraft to its targeted landing site while satisfying the planetary protection requirements in the presence of flight system constraints.

  11. Dual-target cost in visual search for multiple unfamiliar faces.

    Mestry, Natalie; Menneer, Tamaryn; Cave, Kyle R; Godwin, Hayward J; Donnelly, Nick

    2017-08-01

    The efficiency of visual search for one (single-target) and either of two (dual-target) unfamiliar faces was explored to understand the manifestations of capacity and guidance limitations in face search. The visual similarity of distractor faces to target faces was manipulated using morphing (Experiments 1 and 2) and multidimensional scaling (Experiment 3). A dual-target cost was found in all experiments, evidenced by slower and less accurate search in dual- than single-target conditions. The dual-target cost was unequal across the targets, with performance being maintained on one target and reduced on the other, which we label "preferred" and "non-preferred" respectively. We calculated the capacity for each target face and show reduced capacity for representing the non-preferred target face. However, results show that the capacity for the non-preferred target can be increased when the dual-target condition is conducted after participants complete the single-target conditions. Analyses of eye movements revealed evidence for weak guidance of fixations in single-target search, and when searching for the preferred target in dual-target search. Overall, the experiments show dual-target search for faces is capacity- and guidance-limited, leading to superior search for 1 face over the other in dual-target search. However, learning faces individually may improve capacity with the second face. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.

    Andrea Trochine

    2014-05-01

    Full Text Available The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn. Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi.

  13. GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target

    Herath, N I; Rocques, N; Garancher, A; Eychène, A; Pouponnot, C

    2014-01-01

    Multiple myeloma (MM) is an incurable haematological malignancy characterised by the proliferation of mature antibody-secreting plasma B cells in the bone marrow. MM can arise from initiating translocations, of which the musculoaponeurotic fibrosarcoma (MAF) family is implicated in ∼5%. MMs bearing Maf translocations are of poor prognosis. These translocations are associated with elevated Maf expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20) translocations, involving c-MAF and MAFB, respectively. c-MAF is also overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We show that LiCl-induced GSK3 inhibition targets these phosphorylations and specifically decreases proliferation and colony formation of Maf-expressing MM cell lines. Interestingly, bortezomib induced stabilisation of Maf phosphorylation, an observation that could explain, at least partially, the low efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3 inhibition could represent a new therapeutic approach for these patients

  14. Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

    Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

    2018-04-18

    Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

  15. An individual differences approach to multiple-target visual search errors: How search errors relate to different characteristics of attention.

    Adamo, Stephen H; Cain, Matthew S; Mitroff, Stephen R

    2017-12-01

    A persistent problem in visual search is that searchers are more likely to miss a target if they have already found another in the same display. This phenomenon, the Subsequent Search Miss (SSM) effect, has remained despite being a known issue for decades. Increasingly, evidence supports a resource depletion account of SSM errors-a previously detected target consumes attentional resources leaving fewer resources available for the processing of a second target. However, "attention" is broadly defined and is composed of many different characteristics, leaving considerable uncertainty about how attention affects second-target detection. The goal of the current study was to identify which attentional characteristics (i.e., selection, limited capacity, modulation, and vigilance) related to second-target misses. The current study compared second-target misses to an attentional blink task and a vigilance task, which both have established measures that were used to operationally define each of four attentional characteristics. Second-target misses in the multiple-target search were correlated with (1) a measure of the time it took for the second target to recovery from the blink in the attentional blink task (i.e., modulation), and (2) target sensitivity (d') in the vigilance task (i.e., vigilance). Participants with longer recovery and poorer vigilance had more second-target misses in the multiple-target visual search task. The results add further support to a resource depletion account of SSM errors and highlight that worse modulation and poor vigilance reflect a deficit in attentional resources that can account for SSM errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A unified flight control methodology for a compound rotorcraft in fundamental and aerobatic maneuvering flight

    Thorsen, Adam

    This study investigates a novel approach to flight control for a compound rotorcraft in a variety of maneuvers ranging from fundamental to aerobatic in nature. Fundamental maneuvers are a class of maneuvers with design significance that are useful for testing and tuning flight control systems along with uncovering control law deficiencies. Aerobatic maneuvers are a class of aggressive and complex maneuvers with more operational significance. The process culminating in a unified approach to flight control includes various control allocation studies for redundant controls in trim and maneuvering flight, an efficient methodology to simulate non-piloted maneuvers with varying degrees of complexity, and the setup of an unconventional control inceptor configuration along with the use of a flight simulator to gather pilot feedback in order to improve the unified control architecture. A flight path generation algorithm was developed to calculate control inceptor commands required for a rotorcraft in aerobatic maneuvers. This generalized algorithm was tailored to generate flight paths through optimization methods in order to satisfy target terminal position coordinates or to minimize the total time of a particular maneuver. Six aerobatic maneuvers were developed drawing inspiration from air combat maneuvers of fighter jet aircraft: Pitch-Back Turn (PBT), Combat Ascent Turn (CAT), Combat Descent Turn (CDT), Weaving Pull-up (WPU), Combat Break Turn (CBT), and Zoom and Boom (ZAB). These aerobatic maneuvers were simulated at moderate to high advance ratios while fundamental maneuvers of the compound including level accelerations/decelerations, climbs, descents, and turns were investigated across the entire flight envelope to evaluate controller performance. The unified control system was developed to allow controls to seamlessly transition between manual and automatic allocations while ensuring that the axis of control for a particular inceptor remained constant with flight

  17. The Art and Science of Operational Maneuver,

    1988-05-04

    Classification) The Art and Science of Operational Maneuver (U) 12. PERSONAL AUTHOR(S) MAJ Joseph Schroedel 13a. TYPE OF REPORT 13b. TIME COVERED 14...CLASSIFICATION OF THIS PAGE VA) CL LA S F1 EP {fJE ART ANQ SCIENCE OlF OPERAIl NAL MANUVER By6 Mal or Josepi~ Schroeci, L U. S. Arm~y H Aciv -darILC Ced M ili t...Studies ,nIgz’raph ApprovwA. Name of Student: Major Jonevh Schroedel. U.S. Army Title ot Monograph: The Art and Science of Operational Maneuver Approved By

  18. Cassini Solstice Mission Maneuver Experience: Year Two

    Arrieta, Juan; Ballard, Christopher G.; Hahn, Yungsun

    2012-01-01

    The Cassini Spacecraft was launched in October 1997 on a mission to observe Saturn and its moons; it entered orbit around Saturn in July 2004 for a nominal four-year Prime Mission, later augmented by two extensions: the Equinox Mission, from July 2008 through September 2010, and the Solstice Mission, from October 2010 through September 2017. This paper provides an overview of the maneuver activities from August 2011 through June 2012 which include the design of 38 Orbit Trim Maneuvers--OTM-288 through OTM-326-- for attaining 14 natural satellite encounters: seven with Titan, six with Enceladus, and one with Dione.

  19. Targeting a heterologous protein to multiple plant organelles via rationally designed 5? mRNA tags

    Voges, M.J.; Silver, P.A.; Way, J.C.; Mattozzi, M.D.

    2013-01-01

    Background Plant bioengineers require simple genetic devices for predictable localization of heterologous proteins to multiple subcellular compartments. Results We designed novel hybrid signal sequences for multiple-compartment localization and characterize their function when fused to GFP in

  20. Time-resolved x-ray line emission studies of thermal transport in multiple beam uv-irradiated targets

    Jaanimagi, P.A.; Henke, B.L.; Delettrez, J.; Richardson, M.C.

    1984-01-01

    Thermal transport in spherical targets irradiated with multiple, nanosecond duration laser beams, has been a topic of much discussion recently. Different inferences on the level of thermal flux inhibition have been drawn from plasma velocity and x-ray spectroscopic diagnostics. We present new measurements of thermal transport on spherical targets made through time-resolved x-ray spectroscopic measurements of the progress of the ablation surface through thin layers of material on the surface of the target. These measurements, made with 6 and 12 uv (351 nm) nanosecond beams from OMEGA, will be compared to previous thermal transport measurements. Transparencies of the conference presentation are given

  1. Sphingosine 1-Phosphate Receptor 1 as a Useful Target for Treatment of Multiple Sclerosis

    Kunitomo Adachi

    2012-05-01

    Full Text Available Sphingosine 1-phosphate (S1P, a lysophospholipid mediator, is generated from sphingosine by sphingosine kinases and binds five known cell surface receptors. S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from secondary lymphoid organs (SLO, as evinced by the inability of lymphocytes to exit from the SLO in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active, S1P receptor modulator with a structure closely related to sphingosine. FTY720 was first synthesized by chemical modification of a natural product, myriocin. FTY720 is effectively converted to an active metabolite, FTY720 phosphate (FTY720-P by sphingosine kinases. FTY720-P shows high affinity to 4 of the S1P receptors (S1P1, S1P3, S1P4, and S1P5. In particular, FTY720-P strongly induces internalization and degradation of S1P1, inhibits S1P responsiveness of lymphocytes in the SLO, and acts as a functional antagonist at lymphocytic S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO to decrease circulation of lymphocytes including autoreactive Th17 cells and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Because FTY720 shows a superior efficacy in relapsing remitting MS patients compared to intramuscular interferon-β-1a (Avonex®, S1P1 is presumed to be a useful target for the therapy of MS.

  2. Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.

    Marimuthu, Srinivasan; Chivukula, Raghavender S V; Alfonso, Lloyd F; Moridani, Majid; Hagen, Fred K; Bhat, G Jayarama

    2011-11-01

    Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

  3. Assisting People with Multiple Disabilities by Improving Their Computer Pointing Efficiency with an Automatic Target Acquisition Program

    Shih, Ching-Hsiang; Shih, Ching-Tien; Peng, Chin-Ling

    2011-01-01

    This study evaluated whether two people with multiple disabilities would be able to improve their pointing performance through an Automatic Target Acquisition Program (ATAP) and a newly developed mouse driver (i.e. a new mouse driver replaces standard mouse driver, and is able to monitor mouse movement and intercept click action). Initially, both…

  4. Estimating Single and Multiple Target Locations Using K-Means Clustering with Radio Tomographic Imaging in Wireless Sensor Networks

    2015-03-26

    clustering is an algorithm that has been used in data mining applications such as machine learning applications , pattern recognition, hyper-spectral imagery...42 3.7.2 Application of K-means Clustering . . . . . . . . . . . . . . . . . 42 3.8 Experiment Design...Tomographic Imaging WLAN Wireless Local Area Networks WSN Wireless Sensor Network xx ESTIMATING SINGLE AND MULTIPLE TARGET LOCATIONS USING K-MEANS CLUSTERING

  5. Dynamic diffraction-limited light-coupling of 3D-maneuvered wave-guided optical waveguides.

    Villangca, Mark; Bañas, Andrew; Palima, Darwin; Glückstad, Jesper

    2014-07-28

    We have previously proposed and demonstrated the targeted-light delivery capability of wave-guided optical waveguides (WOWs). As the WOWs are maneuvered in 3D space, it is important to maintain efficient light coupling through the waveguides within their operating volume. We propose the use of dynamic diffractive techniques to create diffraction-limited spots that will track and couple to the WOWs during operation. This is done by using a spatial light modulator to encode the necessary diffractive phase patterns to generate the multiple and dynamic coupling spots. The method is initially tested for a single WOW and we have experimentally demonstrated dynamic tracking and coupling for both lateral and axial displacements.

  6. Dynamic diffraction-limited light-coupling of 3D-maneuvered wave-guided optical waveguides

    Villangca, Mark Jayson; Bañas, Andrew Rafael; Palima, Darwin

    2014-01-01

    We have previously proposed and demonstrated the targeted-light delivery capability of wave-guided optical waveguides (WOWs). As the WOWs are maneuvered in 3D space, it is important to maintain efficient light coupling through the waveguides within their operating volume. We propose the use...... of dynamic diffractive techniques to create diffraction-limited spots that will track and couple to the WOWs during operation. This is done by using a spatial light modulator to encode the necessary diffractive phase patterns to generate the multiple and dynamic coupling spots. The method is initially tested...... for a single WOW and we have experimentally demonstrated dynamic tracking and coupling for both lateral and axial displacements....

  7. Precision Closed-Loop Orbital Maneuvering System Design and Performance for the Magnetospheric Multi-Scale Mission (MMS) Formation

    Chai, Dean; Queen, Steve; Placanica, Sam

    2015-01-01

    NASA's Magnetospheric Multi-Scale (MMS) mission successfully launched on March 13, 2015 (UTC) consists of four identically instrumented spin-stabilized observatories that function as a constellation to study magnetic reconnection in space. The need to maintain sufficiently accurate spatial and temporal formation resolution of the observatories must be balanced against the logistical constraints of executing overly-frequent maneuvers on a small fleet of spacecraft. These two considerations make for an extremely challenging maneuver design problem. This paper focuses on the design elements of a 6-DOF spacecraft attitude control and maneuvering system capable of delivering the high-precision adjustments required by the constellation designers---specifically, the design, implementation, and on-orbit performance of the closed-loop formation-class maneuvers that include initialization, maintenance, and re-sizing. The maneuvering control system flown on MMS utilizes a micro-gravity resolution accelerometer sampled at a high rate in order to achieve closed-loop velocity tracking of an inertial target with arc-minute directional and millimeter-per-second magnitude accuracy. This paper summarizes the techniques used for correcting bias drift, sensor-head offsets, and centripetal aliasing in the acceleration measurements. It also discusses the on-board pre-maneuver calibration and compensation algorithms as well as the implementation of the post-maneuver attitude adjustments.

  8. Near Earth Asteroid redirect missions based on gravity assist maneuver

    Ledkov, Anton; Shustov, Boris M.; Eismont, Natan; Boyarsky, Michael; Nazirov, Ravil; Fedyaev, Konstantin

    During last years several events attracted world community attention to the hazards of hitting the Earth by sky objects. One of these objects is Apophis asteroid what was expected with nonzero probability to hit the Earth in 2036. Luckily after more precise measurements this event is considered as practically improbable. But the other object has really reached the Earth, entered the atmosphere in the Chelyabinsk area and caused vast damages. After this the hazardous near Earth objects problem received practical confirmation of the necessity to find the methods of its resolution. The methods to prevent collision of the dangerous sky object with the Earth proposed up to now look not practical enough if one mentions such as gravitational tractor or changing the reflectivity of the asteroid surface. Even the method supposing the targeting of the spacecraft to the hazardous object in order to deflect it from initial trajectory by impact does not work because its low mass as compared with the mass of asteroid to be deflected. For example the mass of the Apophis is estimated to be about 40 million tons but the spacecraft which can be launched to intercept the asteroid using contemporary launchers has the mass not more than 5 tons. So the question arises where to find the heavier projectile which is possible to direct to the dangerous object? The answer proposed in our paper is very simple: to search it among small near Earth asteroids. As small ones we suppose those which have the cross section size not more than 12-15 meters and mass not exceeding 1500 -1700 tons. According to contemporary estimates the number of such asteroids is not less than 100000. The other question is how to redirect such asteroid to the dangerous one. In the paper the possibilities are studied to use for that purpose gravity assist maneuvers near Earth. It is shown that even among asteroids included in contemporary catalogue there are the ones which could be directed to the trajectory of the

  9. Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

    Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

    2018-01-01

    Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

  10. 32 CFR 644.137 - Maneuver agreements.

    2010-07-01

    ... planning and acquires rights to use land and other facilities for Department of the Army exercises. The... and, after the maneuver is completed, will be responsible for negotiating restoration settlements and... director at field level whereby the command will assume responsibility for settlement of real estate...

  11. Optimizing interplanetary trajectories with deep space maneuvers

    Navagh, John

    1993-09-01

    Analysis of interplanetary trajectories is a crucial area for both manned and unmanned missions of the Space Exploration Initiative. A deep space maneuver (DSM) can improve a trajectory in much the same way as a planetary swingby. However, instead of using a gravitational field to alter the trajectory, the on-board propulsion system of the spacecraft is used when the vehicle is not near a planet. The purpose is to develop an algorithm to determine where and when to use deep space maneuvers to reduce the cost of a trajectory. The approach taken to solve this problem uses primer vector theory in combination with a non-linear optimizing program to minimize Delta(V). A set of necessary conditions on the primer vector is shown to indicate whether a deep space maneuver will be beneficial. Deep space maneuvers are applied to a round trip mission to Mars to determine their effect on the launch opportunities. Other studies which were performed include cycler trajectories and Mars mission abort scenarios. It was found that the software developed was able to locate quickly DSM's which lower the total Delta(V) on these trajectories.

  12. Helicopter noise footprint prediction in unsteady maneuvers

    Gennaretti, Massimo; Bernardini, Giovanni; Serafini, Jacopo; Anobile, A.; Hartjes, S.

    2017-01-01

    This paper investigates different methodologies for the evaluation of the acoustic disturbance emitted by helicopter’s main rotors during unsteady maneuvers. Nowadays, the simulation of noise emitted by helicopters is of great interest to designers, both for the assessment of the acoustic impact

  13. About avatars and maneuvering in virtual environments

    Delleman, N.

    2006-01-01

    This paper is about the use of avatars and maneuvering in virtual environments for simulation-based design ergonomics. An avatar is a digital human model driven by an instrumented human who is immersed in a virtual environment. A presentation on locomotion devices is followed by descriptions of

  14. Demonstrative Maneuvers for Aircraft Agility Predictions

    2008-03-01

    AIAA Paper 1996-3741. 19. Raymer , Daniel P. Aircraft Design: A Conceptual Approach. American Institute of Aeronautics and Astronautics, Inc., 3rd...Shaw, Robert L. Fighter Combat: Tactics and Maneuvering. Naval Institute Press, Annapolis, MD, 1985. 25. Smith, Steven W. The Scientist and

  15. Kristeller maneuvers or fundal pressure and maternal/neonatal morbidity: obstetric and judicial literature review.

    Malvasi, Antonio; Zaami, Simona; Tinelli, Andrea; Trojano, Giuseppe; Montanari Vergallo, Gianluca; Marinelli, Enrico

    2018-02-21

    A significant amount of data concerning maternal-fetal damage arising from the exertion of Kristeller maneuvers (KMs) or fundal pressure (FP) go unreleased due to medicolegal implications. For this reason, the paper gathers information as to the real magnitude of litigation related to FP-induced damages and injuries. The authors have undertaken a research in order to include general search engines (PubMed-Medline, Cochrane, Embase, Google, GyneWeb) and legal databases (De Jure, Italian database of jurisprudence daily update; Westlaw, Thomson Reuters, American ruling database and Bailii, UK Court Ruling Database). Results confirm said phenomenon to be more wide ranging than it appears through official channels. Several courts of law, both in the United States of America (USA) and in European Union (EU) Member States as well, have ruled against the use of the maneuver itself, assuming a stance conducive to a presumption of guilt against those doctors and healthcare providers who resorted to KMs or FP during deliveries. Given how rife FP is in mainstream obstetric practice, it is as if there were a wide gap between obstetric real-life and what official jurisprudence and healthcare institutions-sanctioned official practices are. The authors think that it would be desirable to draft specifically targeted guidelines or recommendations on maneuvers during vaginal delivery, in which to point out exactly what kinds of maneuvering techniques are to be absolutely banned and what maneuvers are to be allowed, and under what conditions their application can be considered appropriate.

  16. Mars Exploration Rovers Launch Performance and TCM-1 Maneuver Design

    Kangas, Julie A.; Potts, Christopher L.; Raofi, Behzad

    2004-01-01

    The Mars Exploration Rover (MER) project successfully landed two identical rovers on Mars in order to remotely conduct geologic investigations, including characterization of rocks and soils that may hold clues to past water activity. Two landing sites, Gusev crater and Meridiani Planum, were selected out of nearly 200 candidate sites after balancing science returns and flight system engineering and safety. Precise trajectory targeting and control was necessary to achieve the atmospheric entry requirements for the selected landing sites within the flight system constraints. This paper discusses the expected and achieved launch vehicle performance and the impacts of that performance on the first Trajectory Correction Maneuver (TCM-1) while maintaining targeting flexibility in accommodating additional project concerns about landing site safety and possible in-flight retargeting to alternate landing sites.

  17. 23 CFR 660.517 - Maneuver area roads.

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Maneuver area roads. 660.517 Section 660.517 Highways... PROGRAMS (DIRECT FEDERAL) Defense Access Roads § 660.517 Maneuver area roads. (a) Claims by a highway agency for costs incurred to restore, to their former condition, roads damaged by maneuvers involving a...

  18. Bi-objective optimization of a multiple-target active debris removal mission

    Bérend, Nicolas; Olive, Xavier

    2016-05-01

    The increasing number of space debris in Low-Earth Orbit (LEO) raises the question of future Active Debris Removal (ADR) operations. Typical ADR scenarios rely on an Orbital Transfer Vehicle (OTV) using one of the two following disposal strategies: the first one consists in attaching a deorbiting kit, such as a solid rocket booster, to the debris after rendezvous; with the second one, the OTV captures the debris and moves it to a low-perigee disposal orbit. For multiple-target ADR scenarios, the design of such a mission is very complex, as it involves two optimization levels: one for the space debris sequence, and a second one for the "elementary" orbit transfer strategy from a released debris to the next one in the sequence. This problem can be seen as a Time-Dependant Traveling Salesman Problem (TDTSP) with two objective functions to minimize: the total mission duration and the total propellant consumption. In order to efficiently solve this problem, ONERA has designed, under CNES contract, TOPAS (Tool for Optimal Planning of ADR Sequence), a tool that implements a Branch & Bound method developed in previous work together with a dedicated algorithm for optimizing the "elementary" orbit transfer. A single run of this tool yields an estimation of the Pareto front of the problem, which exhibits the trade-off between mission duration and propellant consumption. We first detail our solution to cope with the combinatorial explosion of complex ADR scenarios with 10 debris. The key point of this approach is to define the orbit transfer strategy through a small set of parameters, allowing an acceptable compromise between the quality of the optimum solution and the calculation cost. Then we present optimization results obtained for various 10 debris removal scenarios involving a 15-ton OTV, using either the deorbiting kit or the disposal orbit strategy. We show that the advantage of one strategy upon the other depends on the propellant margin, the maximum duration allowed

  19. Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

    Cleanthous, Sophie; Strzok, Sara; Pompilus, Farrah; Cano, Stefan; Marquis, Patrick; Cohan, Stanley; Goldman, Myla D; Kresa-Reahl, Kiren; Petrillo, Jennifer; Castrillo-Viguera, Carmen; Cadavid, Diego; Chen, Shih-Yin

    2018-01-01

    ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

  20. Effective source of bremsstrahlung with multiple crossing of a thin target by an electron beam

    Grishin, V.K.; Ishkhanov, B.S.; Shvedunov, V.I.

    1996-01-01

    A basically new scheme of electron beam discharge to the target for x ray and gamma radiation generation is proposed. In this case an accelerated electron beam crosses a thin braking target many times, which substantially increases the integral radiation yield. 3 refs.; 2 figs

  1. Detection and Identification of Multiple Stationary Human Targets Via Bio-Radar Based on the Cross-Correlation Method

    Yang Zhang

    2016-10-01

    Full Text Available Ultra-wideband (UWB radar has been widely used for detecting human physiological signals (respiration, movement, etc. in the fields of rescue, security, and medicine owing to its high penetrability and range resolution. In these applications, especially in rescue after disaster (earthquake, collapse, mine accident, etc., the presence, number, and location of the trapped victims to be detected and rescued are the key issues of concern. Ample research has been done on the first issue, whereas the identification and localization of multi-targets remains a challenge. False positive and negative identification results are two common problems associated with the detection of multiple stationary human targets. This is mainly because the energy of the signal reflected from the target close to the receiving antenna is considerably stronger than those of the targets at further range, often leading to missing or false recognition if the identification method is based on the energy of the respiratory signal. Therefore, a novel method based on cross-correlation is proposed in this paper that is based on the relativity and periodicity of the signals, rather than on the energy. The validity of this method is confirmed through experiments using different scenarios; the results indicate a discernible improvement in the detection precision and identification of the multiple stationary targets.

  2. Detection and Identification of Multiple Stationary Human Targets Via Bio-Radar Based on the Cross-Correlation Method.

    Zhang, Yang; Chen, Fuming; Xue, Huijun; Li, Zhao; An, Qiang; Wang, Jianqi; Zhang, Yang

    2016-10-27

    Ultra-wideband (UWB) radar has been widely used for detecting human physiological signals (respiration, movement, etc.) in the fields of rescue, security, and medicine owing to its high penetrability and range resolution. In these applications, especially in rescue after disaster (earthquake, collapse, mine accident, etc.), the presence, number, and location of the trapped victims to be detected and rescued are the key issues of concern. Ample research has been done on the first issue, whereas the identification and localization of multi-targets remains a challenge. False positive and negative identification results are two common problems associated with the detection of multiple stationary human targets. This is mainly because the energy of the signal reflected from the target close to the receiving antenna is considerably stronger than those of the targets at further range, often leading to missing or false recognition if the identification method is based on the energy of the respiratory signal. Therefore, a novel method based on cross-correlation is proposed in this paper that is based on the relativity and periodicity of the signals, rather than on the energy. The validity of this method is confirmed through experiments using different scenarios; the results indicate a discernible improvement in the detection precision and identification of the multiple stationary targets.

  3. Distributed Cooperative Search Control Method of Multiple UAVs for Moving Target

    Chang-jian Ru

    2015-01-01

    Full Text Available To reduce the impact of uncertainties caused by unknown motion parameters on searching plan of moving targets and improve the efficiency of UAV’s searching, a novel distributed Multi-UAVs cooperative search control method for moving target is proposed in this paper. Based on detection results of onboard sensors, target probability map is updated using Bayesian theory. A Gaussian distribution of target transition probability density function is introduced to calculate prediction probability of moving target existence, and then target probability map can be further updated in real-time. A performance index function combining with target cost, environment cost, and cooperative cost is constructed, and the cooperative searching problem can be transformed into a central optimization problem. To improve computational efficiency, the distributed model predictive control method is presented, and thus the control command of each UAV can be obtained. The simulation results have verified that the proposed method can avoid the blindness of UAV searching better and improve overall efficiency of the team effectively.

  4. Single-Isocenter Multiple-Target Stereotactic Radiosurgery: Risk of Compromised Coverage

    Roper, Justin; Chanyavanich, Vorakarn; Betzel, Gregory; Switchenko, Jeffrey; Dhabaan, Anees

    2015-01-01

    Purpose: To determine the dosimetric effects of rotational errors on target coverage using volumetric modulated arc therapy (VMAT) for multitarget stereotactic radiosurgery (SRS). Methods and Materials: This retrospective study included 50 SRS cases, each with 2 intracranial planning target volumes (PTVs). Both PTVs were planned for simultaneous treatment to 21 Gy using a single-isocenter, noncoplanar VMAT SRS technique. Rotational errors of 0.5°, 1.0°, and 2.0° were simulated about all axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using multivariate analysis to determine how PTV coverage was related to PTV volume, PTV separation, and rotational error. Results: At 0.5° rotational error, D95 values and V95 coverage rates were ≥95% in all cases. For rotational errors of 1.0°, 7% of targets had D95 and V95 values 95% for only 63% of the targets. Multivariate analysis showed that PTV volume and distance to isocenter were strong predictors of target coverage. Conclusions: The effects of rotational errors on target coverage were studied across a broad range of SRS cases. In general, the risk of compromised coverage increased with decreasing target volume, increasing rotational error and increasing distance between targets. Multivariate regression models from this study may be used to quantify the dosimetric effects of rotational errors on target coverage given patient-specific input parameters of PTV volume and distance to isocenter.

  5. Estimating maneuvers for precise relative orbit determination using GPS

    Allende-Alba, Gerardo; Montenbruck, Oliver; Ardaens, Jean-Sébastien; Wermuth, Martin; Hugentobler, Urs

    2017-01-01

    Precise relative orbit determination is an essential element for the generation of science products from distributed instrumentation of formation flying satellites in low Earth orbit. According to the mission profile, the required formation is typically maintained and/or controlled by executing maneuvers. In order to generate consistent and precise orbit products, a strategy for maneuver handling is mandatory in order to avoid discontinuities or precision degradation before, after and during maneuver execution. Precise orbit determination offers the possibility of maneuver estimation in an adjustment of single-satellite trajectories using GPS measurements. However, a consistent formulation of a precise relative orbit determination scheme requires the implementation of a maneuver estimation strategy which can be used, in addition, to improve the precision of maneuver estimates by drawing upon the use of differential GPS measurements. The present study introduces a method for precise relative orbit determination based on a reduced-dynamic batch processing of differential GPS pseudorange and carrier phase measurements, which includes maneuver estimation as part of the relative orbit adjustment. The proposed method has been validated using flight data from space missions with different rates of maneuvering activity, including the GRACE, TanDEM-X and PRISMA missions. The results show the feasibility of obtaining precise relative orbits without degradation in the vicinity of maneuvers as well as improved maneuver estimates that can be used for better maneuver planning in flight dynamics operations.

  6. Less is more : The effect of multiple implementation intentions targeting unhealthy snacking habits

    Verhoeven, A.A.C.; Adriaanse, M.A.; de Ridder, D.T.D.; de Vet, E.; Fennis, B.M.

    Implementation intentions have been shown to effectively change counter-intentional habits. Research has, however, almost solely been concerned with the effectiveness of a single plan. In the present research, we investigated the behavioral and cognitive implications of making multiple

  7. Less is more: The effect of multiple implementation intentions targeting unhealthy snacking habits

    Verhoeven, A.A.C.; Adriaanse, M.A.; Ridder, de D.T.D.; Vet, de E.W.M.L.; Fennis, B.M.

    2013-01-01

    Implementation intentions have been shown to effectively change counter-intentional habits. Research has, however, almost solely been concerned with the effectiveness of a single plan. In the present research, we investigated the behavioral and cognitive implications of making multiple

  8. Detection and localization of multiple short range targets using FMCW radar signal

    Jardak, Seifallah; Kiuru, Tero; Metso, Mikko; Pursula, Pekka; Hakli, Janne; Hirvonen, Mervi; Ahmed, Sajid; Alouini, Mohamed-Slim

    2016-01-01

    In this paper, a 24 GHz frequency-modulated continuous wave radar is used to detect and localize both stationary and moving targets. Depending on the application, the implemented software offers different modes of operation. For example, it can

  9. Colisional Cloud Debris and Propelled Evasive Maneuvers

    Ferreira, L. S.; Jesus, A. D. C.; Carvalho, T. C. F.; Sousa, R. R.

    2017-10-01

    Space debris clouds exist at various altitudes in the environment outside the Earth. Fragmentation of debris and/or collision between the debris of a cloud increases the amount of debris, producing smaller debris. This event also increases significantly the chances of collision with operational vehicles in orbit. In this work we study clouds of debris that are close to a spacecraft in relation to its distance from the center of the Earth. The results show several layers of colliding debris depending on their size over time of evasive maneuvers of the vehicle. In addition, we have tested such maneuvers for propulsion systems with a linear and exponential mass variation model. The results show that the linear propulsion system is more efficient.

  10. Review of Tracktable for Satellite Maneuver Detection

    Acquesta, Erin C.S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Valicka, Christopher G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hinga, Mark B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ehn, Carollan Beret [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-10-01

    As a tool developed to translate geospatial data into geometrical descriptors, Tracktable offers a highly efficient means to detect anomalous flight and maritime behavior. Following the success of using geometrical descriptors for detecting anomalous trajectory behavior, the question of whether Tracktable could be used to detect satellite maneuvers arose. In answering this question, this re- port will introduce a brief description of how Tracktable has been used in the past, along with an introduction to the fundamental properties of astrodynamics for satellite trajectories. This will then allow us to compare the two problem spaces, addressing how easily the methods used by Tracktable will translate to orbital mechanics. Based on these results, we will then be able to out- line the current limitations as well as possible path forward for using Tracktable to detect satellite maneuvers.

  11. Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

    Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

    2011-01-01

    In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

  12. Energy, target, projectile and multiplicity dependences of intermittency behaviour in high energy O(Si,S) induced interactions

    Adamovich, M.I.; Alexandrov, Y.A.; Chernyavski, M.M.; Gerassimov, S.G.; Kharlamov, S.P.; Larionova, V.G.; Maslennikova, N.V.; Orlova, G.I.; Peresadko, N.G.; Salmanova, N.A.; Tretyakova, M.I.; Ameeva, Z.U.; Andreeva, N.P.; Anzon, Z.V.; Bubnov, V.I.; Chasnikov, I.Y.; Eligbaeva, G.Z.; Eremenko, G.Z.; Gaitinov, A.S.; Kalyachkina, G.S.; Kanygina, E.K.; Skakhova, C.I.; Bhalla, K.B.; Kumar, V.; Lal, P.; Lokanathan, S.; Mookerjee, S.; Raniwala, R.; Raniwala, S.; Burnett, T.H.; Grote, J.; Koss, T.; Lord, J.; Skelding, D.; Strausz, S.C.; Wilkes, R.J.; Cai, X.; Huang, H.; Liu, L.S.; Qian, W.Y.; Wang, H.Q.; Zhou, D.C.; Zhou, J.C.; Chernova, L.P.; Gadzhieva, S.I.; Gulamov, K.G.; Kadyrov, F.G.; Lukicheva, N.S.; Navotny, V.S.; Svechnikova, L.N.; Friedlander, E.M.; Heckman, H.H.; Lindstrom, P.J.; Garpman, S.; Jakobsson, B.; Otterlund, I.; Persson, S.; Soederstroem, K.; Stenlund, E.; Judek, B.; Nasyrov, S.H.; Petrov, N.V.; Xu, G.F.; Zheng, P.Y.

    1991-01-01

    Fluctuations of charged particles in high energy oxygen, silicon and sulphur induced interactions are investigated with the method of scaled factorial moments. It is found that for decreasing bin size down to δη∝0.1 the EMU01 data exhibits intermittent behaviour. The intermittency indexes are found to decrease with increasing incident energy and multiplicity and to increase with increasing target mass. It seems also to increase as the projectile mass increases. (orig.)

  13. Foraging through multiple target categories reveals the flexibility of visual working memory.

    Kristjánsson, Tómas; Kristjánsson, Árni

    2018-02-01

    A key assumption in the literature on visual attention is that templates, actively maintained in visual working memory (VWM), guide visual attention. An important question therefore involves the nature and capacity of VWM. According to load theories, more than one search template can be active at the same time and capacity is determined by the total load rather than a precise number of templates. By an alternative account only one search template can be active within visual working memory at any given time, while other templates are in an accessory state - but do not affect visual selection. We addressed this question by varying the number of targets and distractors in a visual foraging task for 40 targets among 40 distractors in two ways: 1) Fixed-distractor-number, involving two distractor types while target categories varied from one to four. 2) Fixed-color-number (7), so that if the target types were two, distractors types were five, while if target number increased to three, distractor types were four (etc.). The two accounts make differing predictions. Under the single-template account, we should expect large switch costs as target types increase to two, but switch-costs should not increase much as target types increase beyond two. Load accounts predict an approximately linear increase in switch costs with increased target type number. The results were that switch costs increased roughly linearly in both conditions, in line with load accounts. The results are discussed in light of recent proposals that working memory reflects lingering neural activity at various sites that operate on the stimuli in each case and findings showing neurally silent working memory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Identifying tacit strategies in aircraft maneuvers

    Lewis, Charles M.; Heidorn, P. B.

    1991-01-01

    Two machine-learning methods are presently used to characterize the avoidance strategies used by skilled pilots in simulated aircraft encounters, and a general framework for the characterization of the strategic components of skilled behavior via qualitative representation of situations and responses is presented. Descriptions of pilot maneuvers that were 'conceptually equivalent' were ascertained by a concept-learning algorithm in conjunction with a classifier system that employed a generic algorithm; satisficing and 'buggy' strategies were thereby revealed.

  15. Decisive Army Strategic and Expeditionary Maneuver

    2015-05-01

    emerging changes will impact strategic maneuver by 2025. For example, a rapid transition is occurring in the commercial air cargo market where 777...more readily available in the international defense market and in the inventories of potential adversaries. In short, the study team believes HPMs... Cisco Visual Networking Index (VNI), available at: http://www.cisco.com/c/en/us/solutions/collateral/service-provider/visual-networking-index- vni

  16. A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

    Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

    2014-12-05

    Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

  17. The Calibration Target for the Mars 2020 SHERLOC Instrument: Multiple Science Roles for Future Manned and Unmanned Mars Exploration

    Fries, M.; Bhartia, R.; Beegle, L.; Burton, A.; Ross, A.; Shahar, A.

    2014-01-01

    The Scanning Habitable Environments with Raman & Luminescence for Organics & Chemicals (SHERLOC) instrument is a deep ultraviolet (UV) Raman/fluorescence instrument selected as part of the Mars 2020 rover instrument suite. SHERLOC will be mounted on the rover arm and its primary role is to identify carbonaceous species in martian samples, which may be selected for inclusion into a returnable sample cache. The SHERLOC instrument will require the use of a calibration target, and by design, multiple science roles will be addressed in the design of the target. Samples of materials used in NASA Extravehicular Mobility unit (EMU, or "space suit") manufacture have been included in the target to serve as both solid polymer calibration targets for SHERLOC instrument function, as well as for testing the resiliency of those materials under martian ambient conditions. A martian meteorite will also be included in the target to serve as a well-characterized example of a martian rock that contains trace carbonaceous material. This rock will be the first rock that we know of that has completed a round trip between planets and will therefore serve an EPO role to attract public attention to science and planetary exploration. The SHERLOC calibration target will address a wide range of NASA goals to include basic science of interest to both the Science Mission Directorate (SMD) and Human Exploration and Operations Mission Directorate (HEOMD).

  18. SAR image dataset of military ground targets with multiple poses for ATR

    Belloni, Carole; Balleri, Alessio; Aouf, Nabil; Merlet, Thomas; Le Caillec, Jean-Marc

    2017-10-01

    Automatic Target Recognition (ATR) is the task of automatically detecting and classifying targets. Recognition using Synthetic Aperture Radar (SAR) images is interesting because SAR images can be acquired at night and under any weather conditions, whereas optical sensors operating in the visible band do not have this capability. Existing SAR ATR algorithms have mostly been evaluated using the MSTAR dataset.1 The problem with the MSTAR is that some of the proposed ATR methods have shown good classification performance even when targets were hidden,2 suggesting the presence of a bias in the dataset. Evaluations of SAR ATR techniques are currently challenging due to the lack of publicly available data in the SAR domain. In this paper, we present a high resolution SAR dataset consisting of images of a set of ground military target models taken at various aspect angles, The dataset can be used for a fair evaluation and comparison of SAR ATR algorithms. We applied the Inverse Synthetic Aperture Radar (ISAR) technique to echoes from targets rotating on a turntable and illuminated with a stepped frequency waveform. The targets in the database consist of four variants of two 1.7m-long models of T-64 and T-72 tanks. The gun, the turret position and the depression angle are varied to form 26 different sequences of images. The emitted signal spanned the frequency range from 13 GHz to 18 GHz to achieve a bandwidth of 5 GHz sampled with 4001 frequency points. The resolution obtained with respect to the size of the model targets is comparable to typical values obtained using SAR airborne systems. Single polarized images (Horizontal-Horizontal) are generated using the backprojection algorithm.3 A total of 1480 images are produced using a 20° integration angle. The images in the dataset are organized in a suggested training and testing set to facilitate a standard evaluation of SAR ATR algorithms.

  19. miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

    Luo, Chonglin; Tetteh, Paul W; Merz, Patrick R; Dickes, Elke; Abukiwan, Alia; Hotz-Wagenblatt, Agnes; Holland-Cunz, Stefan; Sinnberg, Tobias; Schittek, Birgit; Schadendorf, Dirk; Diederichs, Sven; Eichmüller, Stefan B

    2013-03-01

    MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

  20. DOA Estimation of Low Altitude Target Based on Adaptive Step Glowworm Swarm Optimization-multiple Signal Classification Algorithm

    Zhou Hao

    2015-06-01

    Full Text Available The traditional MUltiple SIgnal Classification (MUSIC algorithm requires significant computational effort and can not be employed for the Direction Of Arrival (DOA estimation of targets in a low-altitude multipath environment. As such, a novel MUSIC approach is proposed on the basis of the algorithm of Adaptive Step Glowworm Swarm Optimization (ASGSO. The virtual spatial smoothing of the matrix formed by each snapshot is used to realize the decorrelation of the multipath signal and the establishment of a fullorder correlation matrix. ASGSO optimizes the function and estimates the elevation of the target. The simulation results suggest that the proposed method can overcome the low altitude multipath effect and estimate the DOA of target readily and precisely without radar effective aperture loss.

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

    Meng, Yan; Gan, Jing; Desai, Sachi

    2008-04-01

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

  2. Damage to preheated tungsten targets after multiple plasma impacts simulating ITER ELMs

    Garkusha, I.E. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine)], E-mail: garkusha@ipp.kharkov.ua; Bandura, A.N.; Byrka, O.V.; Chebotarev, V.V. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Landman, I. [Forschungszentrum Karlsruhe, IHM, 76021 Karlsruhe (Germany); Makhlaj, V.A. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Pestchanyi, S. [Forschungszentrum Karlsruhe, IHM, 76021 Karlsruhe (Germany); Tereshin, V.I. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine)

    2009-04-30

    The behavior of a preheated at 650 deg. C tungsten targets under repetitive ELM-like plasma pulses is studied in simulation experiments with the quasi-stationary plasma accelerator QSPA Kh-50. The targets have been exposed up to 350 pulses of the duration 0.25 ms and the surface heat loads either 0.45 MJ/m{sup 2} or 0.75 MJ/m{sup 2}, which is below and above the melting threshold, respectively. The development of surface morphology of the exposed targets as well as cracking and swelling at the surface is discussed. First comparisons of obtained experimental results with corresponding numerical simulations of the code PEGASUS-3D are presented.

  3. Assessing Multiple Pathways for Achieving China’s National Emissions Reduction Target

    Mingyue Wang

    2018-06-01

    Full Text Available In order to achieve China’s target of carbon intensity emissions reduction in 2030, there is a need to identify a scientific pathway and feasible strategies. In this study, we used stochastic frontier analysis method of energy efficiency, incorporating energy structure, economic structure, human capital, capital stock and potential energy efficiency to identify an efficient pathway for achieving emissions reduction target. We set up 96 scenarios including single factor scenarios and multi-factors combination scenarios for the simulation. The effects of each scenario on achieving the carbon intensity reduction target are then evaluated. It is found that: (1 Potential energy efficiency has the greatest contribution to the carbon intensity emissions reduction target; (2 they are unlikely to reach the 2030 carbon intensity reduction target of 60% by only optimizing a single factor; (3 in order to achieve the 2030 target, several aspects have to be adjusted: the fossil fuel ratio must be lower than 80%, and its average growth rate must be decreased by 2.2%; the service sector ratio in GDP must be higher than 58.3%, while the growth rate of non-service sectors must be lowered by 2.4%; and both human capital and capital stock must achieve and maintain a stable growth rate and a 1% increase annually in energy efficiency. Finally, the specific recommendations of this research were discussed, including constantly improved energy efficiency; the upgrading of China’s industrial structure must be accelerated; emissions reduction must be done at the root of energy sources; multi-level input mechanisms in overall levels of education and training to cultivate the human capital stock must be established; investment in emerging equipment and accelerate the closure of backward production capacity to accumulate capital stock.

  4. Multivariate linear regression of high-dimensional fMRI data with multiple target variables.

    Valente, Giancarlo; Castellanos, Agustin Lage; Vanacore, Gianluca; Formisano, Elia

    2014-05-01

    Multivariate regression is increasingly used to study the relation between fMRI spatial activation patterns and experimental stimuli or behavioral ratings. With linear models, informative brain locations are identified by mapping the model coefficients. This is a central aspect in neuroimaging, as it provides the sought-after link between the activity of neuronal populations and subject's perception, cognition or behavior. Here, we show that mapping of informative brain locations using multivariate linear regression (MLR) may lead to incorrect conclusions and interpretations. MLR algorithms for high dimensional data are designed to deal with targets (stimuli or behavioral ratings, in fMRI) separately, and the predictive map of a model integrates information deriving from both neural activity patterns and experimental design. Not accounting explicitly for the presence of other targets whose associated activity spatially overlaps with the one of interest may lead to predictive maps of troublesome interpretation. We propose a new model that can correctly identify the spatial patterns associated with a target while achieving good generalization. For each target, the training is based on an augmented dataset, which includes all remaining targets. The estimation on such datasets produces both maps and interaction coefficients, which are then used to generalize. The proposed formulation is independent of the regression algorithm employed. We validate this model on simulated fMRI data and on a publicly available dataset. Results indicate that our method achieves high spatial sensitivity and good generalization and that it helps disentangle specific neural effects from interaction with predictive maps associated with other targets. Copyright © 2013 Wiley Periodicals, Inc.

  5. Propulsive maneuver design for the Mars Exploration Rover mission

    Potts, Christopher L.; Kangas, Julie A.; Raofi, Behzad

    2006-01-01

    Starting from approximately 150 candidate Martian landing sites, two distinct sites have been selected for further investigation by sophisticated rovers. The two rovers, named 'Spirit' and 'Opportunity', begin the surface mission respectively to Gusec Crater and Meridiani Planum in January 2004. the rovers are essentially robotic geologists, sent on a mission to research for evidence in the rocks and soil pertaining to the historical presence of water and the ability to possibly sustain life. Before this scientific search can commence, precise trajectory targeting and control is necessary to achieve the entry requirements for the selected landing sites within the constraints of the flight system. The maneuver design challenge is to meet or exceed these requirements while maintaining the necessary design flexibility to accommodate additional project concerns. Opportunities to improve performance and reduce risk based on trajectory control characteristics are also evaluated.

  6. Uncertainty Requirement Analysis for the Orbit, Attitude, and Burn Performance of the 1st Lunar Orbit Insertion Maneuver

    Young-Joo Song

    2016-12-01

    Full Text Available In this study, the uncertainty requirements for orbit, attitude, and burn performance were estimated and analyzed for the execution of the 1st lunar orbit insertion (LOI maneuver of the Korea Pathfinder Lunar Orbiter (KPLO mission. During the early design phase of the system, associate analysis is an essential design factor as the 1st LOI maneuver is the largest burn that utilizes the onboard propulsion system; the success of the lunar capture is directly affected by the performance achieved. For the analysis, the spacecraft is assumed to have already approached the periselene with a hyperbolic arrival trajectory around the moon. In addition, diverse arrival conditions and mission constraints were considered, such as varying periselene approach velocity, altitude, and orbital period of the capture orbit after execution of the 1st LOI maneuver. The current analysis assumed an impulsive LOI maneuver, and two-body equations of motion were adapted to simplify the problem for a preliminary analysis. Monte Carlo simulations were performed for the statistical analysis to analyze diverse uncertainties that might arise at the moment when the maneuver is executed. As a result, three major requirements were analyzed and estimated for the early design phase. First, the minimum requirements were estimated for the burn performance to be captured around the moon. Second, the requirements for orbit, attitude, and maneuver burn performances were simultaneously estimated and analyzed to maintain the 1st elliptical orbit achieved around the moon within the specified orbital period. Finally, the dispersion requirements on the B-plane aiming at target points to meet the target insertion goal were analyzed and can be utilized as reference target guidelines for a mid-course correction (MCC maneuver during the transfer. More detailed system requirements for the KPLO mission, particularly for the spacecraft bus itself and for the flight dynamics subsystem at the ground

  7. All Set! Evidence of Simultaneous Attentional Control Settings for Multiple Target Colors

    Irons, Jessica L.; Folk, Charles L.; Remington, Roger W.

    2012-01-01

    Although models of visual search have often assumed that attention can only be set for a single feature or property at a time, recent studies have suggested that it may be possible to maintain more than one attentional control setting. The aim of the present study was to investigate whether spatial attention could be guided by multiple attentional…

  8. Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target

    Adolph, C.; Aghasyan, M.; Akhunzyanov, R.; Alexeev, M. G.; Alexeev, G. D.; Amoroso, A.; Andrieux, V.; Anfimov, N. V.; Anosov, V.; Augsten, K.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.; Badelek, B.; Balestra, F.; Ball, M.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E. R.; Birsa, R.; Bodlák, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Büchele, M.; Capozza, L.; Chang, W.-C.; Chatterjee, C.; Chiosso, M.; Choi, A.; Chung, S. U.; Cicuttin, A.; Crespo, M.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S. S.; Dasgupta, S.; Denisov, O.; Dhara, L.; Donskov, S. V.; Doshita, N.; Dreisbach, Ch.; Duic, V.; Dünnweber, W.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Finger, M.; Finger jr., M.; Fischer, H.; Franco, C.; Fresne von Hohenesche, N.; Friedrich, J. M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O. P.; Gerassimov, S.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grabmüller, S.; Grasso, A.; Grosse-Perdekapm, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Haas, F.; Hahne, D.; Hamar, G.; von Harrach, D.; Heinsius, F. H.; Heitz, R.; Herrmann, F.; Horikawa, N.; d'Hose, N.; Hsieh, C.-Yu.; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jarý, V.; Joosten, R.; Jörg, P.; Kabuss, E.; Ketzer, B.; Khaustov, G. V.; Khokhlov, Yu. A.; Kisselev, Y.; Klein, F.; Klimaszewski, K.; Koivuniemi, J. H.; Kolosov, V. N.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V. F.; Kotzinian, A. M.; Kouznetsov, O.; Krämer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z. V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R. P.; Lednev, A. A.; Lehmann, A.; Levillain, M.; Levorato, S.; Lian, Y.-S.; Lichtenstadt, J.; Longo, R.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G.; Marianski, B.; Martin, A.; Marzec, J.; Matoušek, R.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.; Meyer, M.; Meyer, W.; Mikhailov, Yu. V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nový, J.; Nowak, W. D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A. G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.-C.; Pereira, F.; Pešek, M.; Peshekhonov, D. V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V. A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Roskot, M.; Rossiyskaya, N. S.; Ryabchikov, D.; Rybnikov, A.; Rychter, A.; Salač, R.; Samoylenko, V. D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I. A.; Sawada, H.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schönning, K.; Seder, E.; Selyunin, A.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolík, J.; Sozzi, F.; Srnka, Aleš; Steffen, D.; Stolarski, M.; Subrt, O.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Thiel, A.; Tosello, F.; Tskhay, V.; Uhl, S.; Veloso, J.; Virius, M.; Vondra, J.; Wallner, S.; Weisrock, T.; Wilfert, M.; Windmolders, R.; Ter Wolbeek, J.; Zaremba, K.; Závada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Zhuravlev, N.; Ziembicki, M.; Zink, A.

    2017-01-01

    Roč. 767, 10 APRIL (2017), s. 133-141 ISSN 0370-2693 R&D Projects: GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : deep inelastic scattering * kaon multiplicities * quark fragmentation functions * strange quark Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Nuclear physics Impact factor: 4.807, year: 2016

  9. Managing multimorbidity: profiles of integrated care approaches targeting people with multiple chronic conditions in Europe.

    Rijken, M.; Hujala, A.; Ginneken, E. van; Melchiorre, M.G.; Groenewegen, P.; Schellevis, F.

    2018-01-01

    In response to the growing populations of people with multiple chronic diseases, new models of care are currently being developed in European countries to better meet the needs of these people. This paper aims to describe the occurrence and characteristics of various types of integrated care

  10. Data fusion from multiple passive sonar nodes for target localisation and false alarm reduction

    Hunter, A.J.; Fillinger, L.; Zampolli, M.; Clarijs, M.C.

    2012-01-01

    A PHD particle filter implementation has been detailed for the fusion of measurements from multiple passive sonar nodes. It has been demonstrated on simulated metadata and on experimental passive acoustic data of divers and small boats collected in an operational port environment. Fusion at the

  11. Development of a real time multiple target, multi camera tracker for civil security applications

    Åkerlund, Hans

    2009-09-01

    A surveillance system has been developed that can use multiple TV-cameras to detect and track personnel and objects in real time in public areas. The document describes the development and the system setup. The system is called NIVS Networked Intelligent Video Surveillance. Persons in the images are tracked and displayed on a 3D map of the surveyed area.

  12. New treatment strategies for multiple myeloma by targeting Bcl-2 and the mevalonate pathway

    Donk, N.W.C.J. van de

    2003-01-01

    Multiple myeloma is a B-lineage neoplasia. Enhanced proliferation and defects in the regulation of programmed cell death account for the expansion of the malignant clone. Emergence of drug resistance is the primary cause of treatment failure in myeloma. Various studies have indicated that inhibition

  13. A Unique Role of Endogenous Visual-Spatial Attention in Rapid Processing of Multiple Targets

    Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

    2011-01-01

    Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions).…

  14. Immuno-Oncology-The Translational Runway for Gene Therapy: Gene Therapeutics to Address Multiple Immune Targets.

    Weß, Ludger; Schnieders, Frank

    2017-12-01

    Cancer therapy is once again experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing only single targets or pathways. Even the combination of several neo-antigens in cancer vaccines is not sufficient for successful, lasting tumor eradication. The focus has therefore shifted to the immune system's role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells. Immune processes, however, require novel concepts beyond the traditional "single-target-single drug" paradigm and need parallel targeting of diverse cells and mechanisms. This review gives a perspective on the role of gene therapy technologies in the evolving immuno-oncology space and identifies gene therapy as a major driver in the development and regulation of effective cancer immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the most prominent technology enabling effective immuno-oncology strategies.

  15. The Design of New HIV-IN Tethered Bifunctional Inhibitors using Multiple Microdomain Targeted Docking.

    Ciubotaru, Mihai; Musat, Mihaela Georgiana; Surleac, Marius; Ionita, Elena; Petrescu, Andrei Jose; Abele, Edgars; Abele, Ramona

    2018-04-05

    Currently used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes, changes these viral enzymes which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex [1] onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Dependability of Data Derived from Time Sampling Methods with Multiple Observation Targets

    Johnson, Austin H.; Chafouleas, Sandra M.; Briesch, Amy M.

    2017-01-01

    In this study, generalizability theory was used to examine the extent to which (a) time-sampling methodology, (b) number of simultaneous behavior targets, and (c) individual raters influenced variance in ratings of academic engagement for an elementary-aged student. Ten graduate-student raters, with an average of 7.20 hr of previous training in…

  17. Charged particles multiplicity in interactions of 3.7 A GeV 28Si with light and heavy target nuclei in nuclear emulsions

    Singh, B.K.; Tuli, S.K.

    1998-01-01

    Results from measurement of multiplicity of different charged particles emitted from the interactions of 3.7 A GeV 28 Si with different target groups in nuclear emulsion and correlations among them are presented. The nature of the dependence of multiplicities of charged particles on the impact parameter is examined. Analysis of data in terms of specific multiplicity for different target groups is performed and the results are discussed in the light of superposition model. (author)

  18. The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to promote RNAi in C. elegans.

    Shirayama, Masaki; Stanney, William; Gu, Weifeng; Seth, Meetu; Mello, Craig C

    2014-04-14

    Argonaute (AGO) proteins are key nuclease effectors of RNAi. Although purified AGOs can mediate a single round of target RNA cleavage in vitro, accessory factors are required for small interfering RNA (siRNA) loading and to achieve multiple-target turnover. To identify AGO cofactors, we immunoprecipitated the C. elegans AGO WAGO-1, which engages amplified small RNAs during RNAi. These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12. rde-12 mutants are deficient in RNAi, including viral suppression, and fail to produce amplified secondary siRNAs and certain endogenous siRNAs (endo-siRNAs). RDE-12 colocalizes with WAGO-1 in germline P granules and in cytoplasmic and perinuclear foci in somatic cells. These findings and our genetic studies suggest that RDE-12 is first recruited to target mRNA by upstream AGOs (RDE-1 and ERGO-1), where it promotes small RNA amplification and/or WAGO-1 loading. Downstream of these events, RDE-12 forms an RNase-resistant (target mRNA-independent) complex with WAGO-1 and may thus have additional functions in target mRNA surveillance and silencing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. A Novel Sensor Selection and Power Allocation Algorithm for Multiple-Target Tracking in an LPI Radar Network

    Ji She

    2016-12-01

    Full Text Available Radar networks are proven to have numerous advantages over traditional monostatic and bistatic radar. With recent developments, radar networks have become an attractive platform due to their low probability of intercept (LPI performance for target tracking. In this paper, a joint sensor selection and power allocation algorithm for multiple-target tracking in a radar network based on LPI is proposed. It is found that this algorithm can minimize the total transmitted power of a radar network on the basis of a predetermined mutual information (MI threshold between the target impulse response and the reflected signal. The MI is required by the radar network system to estimate target parameters, and it can be calculated predictively with the estimation of target state. The optimization problem of sensor selection and power allocation, which contains two variables, is non-convex and it can be solved by separating power allocation problem from sensor selection problem. To be specific, the optimization problem of power allocation can be solved by using the bisection method for each sensor selection scheme. Also, the optimization problem of sensor selection can be solved by a lower complexity algorithm based on the allocated powers. According to the simulation results, it can be found that the proposed algorithm can effectively reduce the total transmitted power of a radar network, which can be conducive to improving LPI performance.

  20. Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis

    Getts, Meghann Teague; Getts, Daniel R.; Kohm, Adam P.; Miller, Stephen D

    2008-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Since current treatments are aimed at nonspecifically down-regulating inflammation and natural mechanisms of repair and remyelination within the CNS are inadequate for recovery of function, MS patients presently only have available treatments that delay symptom progression. The complex nature of this disease means that only multifaceted treatments hold the promise of a cure. Recent studies i...

  1. On the theory of electromagnetic cascades in thin targets and photon multiplicity measurements

    Khokonov, M.Kh.

    2015-02-01

    The partial probabilities of different scenarios of electromagnetic shower processes are calculated in analytical form. It has been shown that these results are important for measurements of the photon multiplicities which occur during above 100 GeV electron radiation in oriented crystals or in the case of interaction of relativistic electrons with powerful Petawatt laser beams. Quantitative analysis of optimal experimental conditions has been performed. The results are applicable for above few GeV electrons and gamma quanta.

  2. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  3. WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures

    Kenyon Colin

    2009-05-01

    Full Text Available Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR, and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software

  4. Aqua/Aura Updated Inclination Adjust Maneuver Performance Prediction Model

    Boone, Spencer

    2017-01-01

    This presentation will discuss the updated Inclination Adjust Maneuver (IAM) performance prediction model that was developed for Aqua and Aura following the 2017 IAM series. This updated model uses statistical regression methods to identify potential long-term trends in maneuver parameters, yielding improved predictions when re-planning past maneuvers. The presentation has been reviewed and approved by Eric Moyer, ESMO Deputy Project Manager.

  5. Marine Corps Maneuver Squad Leader Mastery Model

    2012-12-17

    H. L., & Dreyfus, S. E. (1986). Mind over machine: The power of human intuitive expertise in the  era of the computer. New York: The  Free  Press...at them then  squat  down to begin playing a dice game. The  maneuver squad leader judged this behavior as an anomaly, because  the boys didn’t begin

  6. Coordination Logic for Repulsive Resolution Maneuvers

    Narkawicz, Anthony J.; Munoz, Cesar A.; Dutle, Aaron M.

    2016-01-01

    This paper presents an algorithm for determining the direction an aircraft should maneuver in the event of a potential conflict with another aircraft. The algorithm is implicitly coordinated, meaning that with perfectly reliable computations and information, it will in- dependently provide directional information that is guaranteed to be coordinated without any additional information exchange or direct communication. The logic is inspired by the logic of TCAS II, the airborne system designed to reduce the risk of mid-air collisions between aircraft. TCAS II provides pilots with only vertical resolution advice, while the proposed algorithm, using a similar logic, provides implicitly coordinated vertical and horizontal directional advice.

  7. Multiplicities of charged pions and unidentified charged hadrons from deep-inelastic scattering of muons off an isoscalar target

    Adolph, C.; Aghasyan, M.; Akhunzyanov, R.; Alexeev, M.G.; Alexeev, G.D.; Amoroso, A.; Andrieux, V.; Anfimov, N.V.; Anosov, V.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.D.R.; Badelek, B.; Balestra, F.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E.R.; Birsa, R.; Bisplinghoff, J.; Bodlak, M.; Boer, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Buechele, M.; Capozza, L.; Chang, W. -C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chung, S. -U.; Cicuttin, A.; Crespo, M.L.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O. Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Duic, V.; Duennweber, W.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Finger, M.; Fischer, H.; Franco, C.; von Hohenesche, N. du Fresne; Friedrich, J.M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grabmueller, S.; Grasso, A.; Grosse Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Haas, F.; Hahne, D.; von Harrach, D.; Hashimoto, R.; Heinsius, F.H.; Heitz, R.; Herrmann, F.; Hinterberger, F.; Horikawa, N.; dHose, N.; Hsieh, C. -Y.; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jary, V.; Joosten, R.; Joerg, P.; Kabuss, E.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu. A.; Kisselev, Yu.; Klein, F.; Klimaszewski, K.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Koenigsmann, K.; Konorov, I.; Konstantinov, V.F.; Kotzinian, A.M.; Kouznetsov, O.M.; Kuhn, R.; Kraemer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z.V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R.P.; Lednev, A.A.; Lehmann, A.; Levillain, M.; Levorato, S.; Lichtenstadt, J.; Longo, R.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G.K.; Marchand, C.; Marianski, B.; Martin, A.; Marzec, J.; Matousek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.V.; Meyer, W.; Michigami, T.; Mikhailov, Yu. V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Montuenga, P.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nikolaenko, V.I.; Novy, J.; Nowak, W.-D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A.G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J. -C.; Pereira, F.; Pesek, M.; Peshekhonov, D.V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Roskot, M.; Ryabchikov, D.I.; Rybnikov, A.; Rychter, A.; Salac, R.; Samoylenko, V.D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I.A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schoenning, K.; Schopferer, S.; Seder, E.; Selyunin, A.; Shevchenko, O. Yu.; Steffen, D.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolik, J.; Sozzi, F.; Srnka, A.; Stolarski, M.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Tosello, F.; Tskhay, V.; Uhl, S.; Veloso, J.; Virius, M.; Vondra, J.; Weisrock, T.; Wilfert, M.; Windmolders, R.; ter Wolbeek, J.; Zaremba, K.; Zavada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Zink, A.

    2017-01-10

    Multiplicities of charged pions and unidentified hadrons produced in deep-inelastic scattering were measured in bins of the Bjorken scaling variable $x$, the relative virtual-photon energy $y$ and the relative hadron energy $z$. Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and an isoscalar target ($^6$LiD). They cover the kinematic domain in the photon virtuality $Q^2$ > 1(GeV/c$)^2$, $0.004 < x < 0.4$, $0.2 < z < 0.85$ and $0.1 < y < 0.7$. In addition, a leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions.

  8. Multiplicities of charged pions and charged hadrons from deep-inelastic scattering of muons off an isoscalar target

    C. Adolph

    2017-01-01

    Full Text Available Multiplicities of charged pions and charged hadrons produced in deep-inelastic scattering were measured in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y and the relative hadron energy z. Data were obtained by the COMPASS Collaboration using a 160GeV muon beam and an isoscalar target (6LiD. They cover the kinematic domain in the photon virtuality Q2>1(GeV/c2, 0.004multiplicity results to extract quark fragmentation functions.

  9. Distributed ISAR Subimage Fusion of Nonuniform Rotating Target Based on Matching Fourier Transform.

    Li, Yuanyuan; Fu, Yaowen; Zhang, Wenpeng

    2018-06-04

    In real applications, the image quality of the conventional monostatic Inverse Synthetic Aperture Radar (ISAR) for the maneuvering target is subject to the strong fluctuation of Radar Cross Section (RCS), as the target aspect varies enormously. Meanwhile, the maneuvering target introduces nonuniform rotation after translation motion compensation which degrades the imaging performance of the conventional Fourier Transform (FT)-based method in the cross-range dimension. In this paper, a method which combines the distributed ISAR technique and the Matching Fourier Transform (MFT) is proposed to overcome these problems. Firstly, according to the characteristics of the distributed ISAR, the multiple channel echoes of the nonuniform rotation target from different observation angles can be acquired. Then, by applying the MFT to the echo of each channel, the defocused problem of nonuniform rotation target which is inevitable by using the FT-based imaging method can be avoided. Finally, after preprocessing, scaling and rotation of all subimages, the noncoherent fusion image containing all the RCS information in all channels can be obtained. The accumulation coefficients of all subimages are calculated adaptively according to the their image qualities. Simulation and experimental data are used to validate the effectiveness of the proposed approach, and fusion image with improved recognizability can be obtained. Therefore, by using the distributed ISAR technique and MFT, subimages of high-maneuvering target from different observation angles can be obtained. Meanwhile, by employing the adaptive subimage fusion method, the RCS fluctuation can be alleviated and more recognizable final image can be obtained.

  10. Behavior learning in differential games and reorientation maneuvers

    Satak, Neha

    method is the Direct Approximation of Value Function (DAVF) method. In this method, unlike the CSR method, the player formulates an objective function for the opponent but does not formulates a strategy directly; rather, indirectly the player assumes that the opponent is playing optimally. Thus, a value function satisfying the HJB equation corresponding to the opponent's cost function exists. The DAVF method finds an approximate solution for the value function based on previous observations of the opponent's control. The approximate solution to the value function is then used to predict the opponent's future behavior. Game examples in which only a single player is learning its opponent's behavior are simulated. Subsequently, examples in which both players in a two-player game are learning each other's behavior are simulated. In the second part of this research, a reorientation control maneuver for a spinning spacecraft will be developed. This will aid the application of behavior learning and differential games concepts to the specific scenario involving multiple spinning spacecraft. An impulsive reorientation maneuver with coasting will be analytically designed to reorient the spin axis of the spacecraft using a single body fixed thruster. Cooperative maneuvers of multiple spacecraft optimizing fuel and relative orientation will be designed. Pareto optimality concepts will be used to arrive at mutually agreeable reorientation maneuvers for the cooperating spinning spacecraft.

  11. C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

    Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

    2011-01-01

    Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

  12. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Coque, Emmanuelle; Raoul, Cédric; Bowerman, Mélissa

    2014-01-01

    Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice. PMID:25221469

  13. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Emmanuelle eCoque

    2014-08-01

    Full Text Available Spinal muscular atrophy (SMA is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the surviving motor neuron 1 (SMN1 gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK, which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myocytes, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice.

  14. ESBWR power maneuvering via feedwater temperature control

    Saha, P.; Marquino, W.; Tucker, L. J.

    2008-01-01

    The ESBWR is a Generation III+ Boiling Water Reactor (BWR) driven by natural circulation. For a given geometry/hardware, system pressure, downcomer water level and feedwater temperature, the core flow rate in the ESBWR is only a function of reactor power, controlled through the control blade movement. In order to provide operational flexibility, another method of core-wide or global power maneuvering via feedwater temperature control has been developed. This is independent of power maneuvering via control blade movement, and it lowers the linear heat generation rate (LHGR) changes near the tip of control blades, which improves fuel reliability. All required stability, anticipated operational occurrences (AOOs), infrequent events, special events including anticipated transients without scram (ATWS), and loss-of-coolant accident (LOCA) analyses have been performed for the 4500 MWt ESBWR. Based on the results of these analyses at 'high', nominal and 'low' feedwater temperatures, a safe Power - Feedwater Temperature operating domain has been developed. This paper summarizes the results of these analyses and presents the ESBWR Power - Feedwater Temperature operating domain or map. (authors)

  15. Anatomical basis of the liver hanging maneuver.

    Trotovsek, Blaz; Belghiti, Jacques; Gadzijev, Eldar M; Ravnik, Dean; Hribernik, Marija

    2005-01-01

    The anterior approach to right hepatectomy using the liver hanging maneuver without liver mobilization claims to be anatomically evaluated. During this procedure a 4 to 6-cm blind dissection between the inferior vena cava and the liver is performed. Short subhepatic veins, entering the inferior vena cava could be torn and a hemorrhage, difficult to control, could occur. On 100 corrosive casts of livers the anterior surface of the inferior vena cava was studied to evaluate the position, diameter and draining area of short subhepatic veins and inferior right hepatic vein. The width of the narrowest point on the planned route of blind dissection was determined. The average value of the narrowest point on the planned route of blind dissection was 8.7+/-2.3mm (range 2-15mm). The ideal angle of dissection being 0 degrees was found in 93% of cases. In 7% we found the angle of 5 degrees toward the right border of inferior vena cava to be the better choice. Our results show that liver hanging maneuver is a safe procedure. With the dissection in the proposed route the risk of disrupting short subhepatic veins is low (7%).

  16. The effects of interventions targeting multiple health behaviors on smoking cessation outcomes: a rapid realist review protocol.

    Minian, Nadia; deRuiter, Wayne K; Lingam, Mathangee; Corrin, Tricia; Dragonetti, Rosa; Manson, Heather; Taylor, Valerie H; Zawertailo, Laurie; Ebnahmady, Arezoo; Melamed, Osnat C; Rodak, Terri; Hahn, Margaret; Selby, Peter

    2018-03-01

    Health behaviors directly impact the health of individuals, and populations. Since individuals tend to engage in multiple unhealthy behaviors such as smoking, excessive alcohol use, physical inactivity, and eating an unhealthy diet simultaneously, many large community-based interventions have been implemented to reduce the burden of disease through the modification of multiple health behaviors. Smoking cessation can be particularly challenging as the odds of becoming dependent on nicotine increase with every unhealthy behavior a smoker exhibits. This paper presents a protocol for a rapid realist review which aims to identify factors associated with effectively changing tobacco use and target two or more additional unhealthy behaviors. An electronic literature search will be conducted using the following bibliographic databases: MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, Social Science Abstracts, Social Work Abstracts, and Web of Science. Two reviewers will screen titles and abstracts for relevant research, and the selected full papers will be used to extract data and assess the quality of evidence. Throughout this process, the rapid realist approach proposed by Saul et al., 2013 will be used to refine our initial program theory and identify contextual factors and mechanisms that are associated with successful multiple health behavior change. This review will provide evidence-based research on the context and mechanisms that may drive the success or failure of interventions designed to support multiple health behavior change. This information will be used to guide curriculum and program development for a government funded project on improving smoking cessation by addressing multiple health behaviors in people in Canada. PROSPERO CRD42017064430.

  17. Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

    Ikeda H

    2015-10-01

    Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

  18. Estimating Accurate Target Coordinates with Magnetic Resonance Images by Using Multiple Phase-Encoding Directions during Acquisition.

    Kim, Minsoo; Jung, Na Young; Park, Chang Kyu; Chang, Won Seok; Jung, Hyun Ho; Chang, Jin Woo

    2018-06-01

    Stereotactic procedures are image guided, often using magnetic resonance (MR) images limited by image distortion, which may influence targets for stereotactic procedures. The aim of this work was to assess methods of identifying target coordinates for stereotactic procedures with MR in multiple phase-encoding directions. In 30 patients undergoing deep brain stimulation, we acquired 5 image sets: stereotactic brain computed tomography (CT), T2-weighted images (T2WI), and T1WI in both right-to-left (RL) and anterior-to-posterior (AP) phase-encoding directions. Using CT coordinates as a reference, we analyzed anterior commissure and posterior commissure coordinates to identify any distortion relating to phase-encoding direction. Compared with CT coordinates, RL-directed images had more positive x-axis values (0.51 mm in T1WI, 0.58 mm in T2WI). AP-directed images had more negative y-axis values (0.44 mm in T1WI, 0.59 mm in T2WI). We adopted 2 methods to predict CT coordinates with MR image sets: parallel translation and selective choice of axes according to phase-encoding direction. Both were equally effective at predicting CT coordinates using only MR; however, the latter may be easier to use in clinical settings. Acquiring MR in multiple phase-encoding directions and selecting axes according to the phase-encoding direction allows identification of more accurate coordinates for stereotactic procedures. © 2018 S. Karger AG, Basel.

  19. Identification of targets and new developments in the treatment of multiple sclerosis – focus on cladribine

    Clemens Warnke

    2010-06-01

    Full Text Available Clemens Warnke1, Heinz Wiendl2, Hans-Peter Hartung1, Olaf Stüve3, Bernd C Kieseier11Department of Neurology, Heinrich-Heine University Düsseldorf, Germany; 2Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Germany; 3Department of Neurology, Dallas VA Medical Center and UT Southwestern Medical Center, Dallas, Texas, USAAbstract: Orally available disease-modifying drugs for relapsing-remitting multiple sclerosis (MS represent an unmet need for this chronic and debilitating disease. Among 5 currently investigated drugs at phase 3 clinical stage, promising efficacy data for fingolimod and oral cladribine have recently been published. However, benefits need to be weighed against the risks to define the role of these compounds within current treatment regimens. In this review, data on the efficacy of a promising compound, oral cladribine, are discussed and balanced with known and anticipated risks in a postmarketing era, and finally gives an outlook on the potential place of this drug in treatment algorithms for MS in the future.Keywords: immunosuppressant, oral drugs, risk–benefit, safety

  20. Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor

    Virginia J. Savin

    2017-01-01

    Full Text Available A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1 as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1 and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.

  1. Whether to target single or multiple CDKs for therapy? That is the question.

    Węsierska-Gądek, Józefa; Maurer, Margarita; Zulehner, Nora; Komina, Oxana

    2011-02-01

    Complexes consisting of cyclin-dependent kinases (CDKs) and their regulatory subunits (the cyclins) control the progression of normal mammalian cells through the cell cycle. However, during malignant transformation this regulatory apparatus malfunctions, allowing cells to undergo unchecked proliferation. In many cases, the high mitotic potential of malignant cells is due to the constitutive activation of CDK-cyclin complexes, facilitated by the inactivation of cellular CDK inhibitors, such as p16(INK4A) or p27(Kip1), and the loss of functional tumor suppressors, such as the p53 and pRb proteins. It has recently been suggested that pharmacological intervention based on remedying the deficiency or loss of activity of these negative regulators of the cell cycle could be a very effective therapeutic option in the treatment of cancer. Multiple CDK inhibitors have been synthesized over the last two decades, spanning at least five classes of compounds. While these inhibitors can be classified on the basis of their chemical structure, it may be more interesting to categorize them according to their pharmacological nature, as broad-spectrum unspecific, pan-specific, or very selective antagonists. This review offers a critical assessment of the advantages and disadvantages of both pan-specific and highly selective CDK inhibitors in therapy. © 2010 Wiley-Liss, Inc.

  2. Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways.

    A R M Ruhul Amin

    Full Text Available Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2.

  3. Correlation between crash avoidance maneuvers and injury severity sustained by motorcyclists in single-vehicle crashes.

    Wang, Chen; Lu, Linjun; Lu, Jian; Wang, Tao

    2016-01-01

    In order to improve motorcycle safety, this article examines the correlation between crash avoidance maneuvers and injury severity sustained by motorcyclists, under multiple precrash conditions. Ten-year crash data for single-vehicle motorcycle crashes from the General Estimates Systems (GES) were analyzed, using partial proportional odds models (i.e., generalized ordered logit models). The modeling results show that "braking (no lock-up)" is associated with a higher probability of increased severity, whereas "braking (lock-up)" is associated with a higher probability of decreased severity, under all precrash conditions. "Steering" is associated with a higher probability of reduced injury severity when other vehicles are encroaching, whereas it is correlated with high injury severity under other conditions. "Braking and steering" is significantly associated with a higher probability of low severity under "animal encounter and object presence," whereas it is surprisingly correlated with high injury severity when motorcycles are traveling off the edge of the road. The results also show that a large number of motorcyclists did not perform any crash avoidance maneuvers or conducted crash avoidance maneuvers that are significantly associated with high injury severity. In general, this study suggests that precrash maneuvers are an important factor associated with motorcyclists' injury severity. To improve motorcycle safety, training/educational programs should be considered to improve safety awareness and adjust driving habits of motorcyclists. Antilock brakes and such systems are also promising, because they could effectively prevent brake lock-up and assist motorcyclists in maneuvering during critical conditions. This study also provides valuable information for the design of motorcycle training curriculum.

  4. Predicting bat colony survival under controls targeting multiple transmission routes of white-nose syndrome.

    Meyer, A D; Stevens, D F; Blackwood, J C

    2016-11-21

    White-nose syndrome (WNS) is a lethal infection of bats caused by the psychrophilic fungus Pseudogymnoascus destructans (Pd). Since the first cases of WNS were documented in 2006, it is estimated that as many as 5.5million bats have succumbed in the United States-one of the fastest mammalian die-offs due to disease ever observed, and the first known sustained epizootic of bats. WNS is contagious between bats, and mounting evidence suggests that a persistent environmental reservoir of Pd plays a significant role in transmission as well. It is unclear, however, the relative contributions of bat-to-bat and environment-to-bat transmission to disease propagation within a colony. We analyze a mathematical model to investigate the consequences of both avenues of transmission on colony survival in addition to the efficacy of disease control strategies. Our model shows that selection of the most effective control strategies is highly dependent on the primary route of WNS transmission. Under all scenarios, however, generalized culling is ineffective and while targeted culling of infected bats may be effective under idealized conditions, it primarily has negative consequences. Thus, understanding the significance of environment-to-bat transmission is paramount to designing effective management plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

    Michalina Hebda

    2016-03-01

    Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

  6. Mapping multiple components of malaria risk for improved targeting of elimination interventions.

    Cohen, Justin M; Le Menach, Arnaud; Pothin, Emilie; Eisele, Thomas P; Gething, Peter W; Eckhoff, Philip A; Moonen, Bruno; Schapira, Allan; Smith, David L

    2017-11-13

    There is a long history of considering the constituent components of malaria risk and the malaria transmission cycle via the use of mathematical models, yet strategic planning in endemic countries tends not to take full advantage of available disease intelligence to tailor interventions. National malaria programmes typically make operational decisions about where to implement vector control and surveillance activities based upon simple categorizations of annual parasite incidence. With technological advances, an enormous opportunity exists to better target specific malaria interventions to the places where they will have greatest impact by mapping and evaluating metrics related to a variety of risk components, each of which describes a different facet of the transmission cycle. Here, these components and their implications for operational decision-making are reviewed. For each component, related mappable malaria metrics are also described which may be measured and evaluated by malaria programmes seeking to better understand the determinants of malaria risk. Implementing tailored programmes based on knowledge of the heterogeneous distribution of the drivers of malaria transmission rather than only consideration of traditional metrics such as case incidence has the potential to result in substantial improvements in decision-making. As programmes improve their ability to prioritize their available tools to the places where evidence suggests they will be most effective, elimination aspirations may become increasingly feasible.

  7. Multi-target QSPR modeling for simultaneous prediction of multiple gas-phase kinetic rate constants of diverse chemicals

    Basant, Nikita; Gupta, Shikha

    2018-03-01

    The reactions of molecular ozone (O3), hydroxyl (•OH) and nitrate (NO3) radicals are among the major pathways of removal of volatile organic compounds (VOCs) in the atmospheric environment. The gas-phase kinetic rate constants (kO3, kOH, kNO3) are thus, important in assessing the ultimate fate and exposure risk of atmospheric VOCs. Experimental data for rate constants are not available for many emerging VOCs and the computational methods reported so far address a single target modeling only. In this study, we have developed a multi-target (mt) QSPR model for simultaneous prediction of multiple kinetic rate constants (kO3, kOH, kNO3) of diverse organic chemicals considering an experimental data set of VOCs for which values of all the three rate constants are available. The mt-QSPR model identified and used five descriptors related to the molecular size, degree of saturation and electron density in a molecule, which were mechanistically interpretable. These descriptors successfully predicted three rate constants simultaneously. The model yielded high correlations (R2 = 0.874-0.924) between the experimental and simultaneously predicted endpoint rate constant (kO3, kOH, kNO3) values in test arrays for all the three systems. The model also passed all the stringent statistical validation tests for external predictivity. The proposed multi-target QSPR model can be successfully used for predicting reactivity of new VOCs simultaneously for their exposure risk assessment.

  8. Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

    Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

    2012-01-01

    In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

  9. Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets.

    Fang Zheng

    2015-02-01

    Full Text Available Targeted therapy based on adjustment of microRNA (miRNAs activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05. In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets.

  10. Targeting poly (ADP-ribose polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells.

    He Huang

    Full Text Available Despite recent pharmaceutical advancements in therapeutic drugs, multiple myeloma (MM remains an incurable disease. Recently, ploy(ADP-ribose polymerase 1 (PARP1 has been shown as a potentially promising target for MM therapy. A previous report suggested bufalin, a component of traditional Chinese medicine ("Chan Su", might target PARP1. However, this hypothesis has not been verified. We here showed that bufalin could inhibit PARP1 activity in vitro and reduce DNA-damage-induced poly(ADP-ribosylation in MM cells. Molecular docking analysis revealed that the active site of bufalin interaction is within the catalytic domain of PAPR1. Thus, PARP1 is a putative target of bufalin. Furthermore, we showed, for the first time that the proliferation of MM cell lines (NCI-H929, U266, RPMI8226 and MM.1S and primary CD138(+ MM cells could be inhibited by bufalin, mainly via apoptosis and G2-M phase cell cycle arrest. MM cell apoptosis was confirmed by apoptotic cell morphology, Annexin-V positive cells, and the caspase3 activation. We further evaluated the role of PARP1 in bufalin-induced apoptosis, discovering that PARP1 overexpression partially suppressed bufalin-induced cell death. Moreover, bufalin can act as chemosensitizer to enhance the cell growth-inhibitory effects of topotecan, camptothecin, etoposide and vorinostat in MM cells. Collectively, our data suggest that bufalin is a novel PARP1 inhibitor and a potentially promising therapeutic agent against MM alone or in combination with other drugs.

  11. 14 CFR 23.155 - Elevator control force in maneuvers.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Elevator control force in maneuvers. 23.155 Section 23.155 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Controllability and Maneuverability § 23.155 Elevator control force in maneuvers. (a) The elevator control force...

  12. Safety analysis of passing maneuvers using extreme value theory

    Haneen Farah

    2017-04-01

    The results indicate that this is a promising approach for safety evaluation. On-going work of the authors will attempt to generalize this method to other safety measures related to passing maneuvers, test it for the detailed analysis of the effect of demographic factors on passing maneuvers' crash probability and for its usefulness in a traffic simulation environment.

  13. Multiple target of hAmylin on rat primary hippocampal neurons.

    Zhang, Nan; Yang, Shengchang; Wang, Chang; Zhang, Jianghua; Huo, Lifang; Cheng, Yiru; Wang, Chuan; Jia, Zhanfeng; Ren, Leiming; Kang, Lin; Zhang, Wei

    2017-02-01

    Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca 2+ homeostasis, the underlying mechanisms have not been fully explored. In this study, we investigated the effects of amylin on rat hippocampal neurons using calcium imaging and whole-cell patch clamp recordings. We demonstrated that the amylin receptor antagonist AC187 abolished the Ca 2+ response induced by low concentrations of human amylin (hAmylin). However, the Ca 2+ response induced by higher concentrations of hAmylin was independent of the amylin receptor. This effect was dependent on extracellular Ca 2+ . Additionally, blockade of L-type Ca 2+ channels partially reduced hAmylin-induced Ca 2+ response. In whole-cell recordings, hAmylin depolarized the membrane potential. Moreover, application of the transient receptor potential (TRP) channel antagonist ruthenium red (RR) attenuated the hAmylin-induced increase in Ca 2+ . Single-cell RT-PCR demonstrated that transient receptor potential vanilloid 4 (TRPV4) mRNA was expressed in most of the hAmylin-responsive neurons. In addition, selective knockdown of TRPV4 channels inhibited the hAmylin-evoked Ca 2+ response. These results indicated that different concentrations of hAmylin act through different pathways. The amylin receptor mediates the excitatory effects of low concentrations of hAmylin. In contrast, for high concentrations of hAmylin, hAmylin aggregates precipitated on the neuronal membrane, activated TRPV4 channels and subsequently triggered membrane voltage-gated calcium channel opening followed by membrane depolarization. Therefore, our data suggest that

  14. Sensitive targeted multiple protein quantification based on elemental detection of Quantum Dots

    Montoro Bustos, Antonio R.; Garcia-Cortes, Marta [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); González-Iglesias, Hector [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Ruiz Encinar, Jorge, E-mail: ruizjorge@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Costa-Fernández, José M. [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Coca-Prados, Miguel [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510 (United States); Sanz-Medel, Alfredo, E-mail: asm@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain)

    2015-06-16

    Highlights: • Novel generic platform for multiparametric quantification of proteins. • QDs labeling and ICP-MS detection allow significant analytical signal amplification. • ICP-MS mass balances information provided an internal validation of the immunoassay. • Multiparametric determination of 5 proteins in human serum samples. • ICP-MS reduced matrix effects as compared to other conventional detection techniques. - Abstract: A generic strategy based on the use of CdSe/ZnS Quantum Dots (QDs) as elemental labels for protein quantification, using immunoassays with elemental mass spectrometry (ICP-MS), detection is presented. In this strategy, streptavidin modified QDs (QDs-SA) are bioconjugated to a biotinylated secondary antibody (b-Ab{sub 2}). After a multi-technique characterization of the synthesized generic platform (QDs-SA-b-Ab{sub 2}) it was applied to the sequential quantification of five proteins (transferrin, complement C3, apolipoprotein A1, transthyretin and apolipoprotein A4) at different concentration levels in human serum samples. It is shown how this generic strategy does only require the appropriate unlabeled primary antibody for each protein to be detected. Therefore, it introduces a way out to the need for the cumbersome and specific bioconjugation of the QDs to the corresponding specific recognition antibody for every target analyte (protein). Results obtained were validated with those obtained using UV–vis spectrophotometry and commercial ELISA Kits. As expected, ICP-MS offered one order of magnitude lower DL (0.23 fmol absolute for transferrin) than the classical spectrophotometric detection (3.2 fmol absolute). ICP-MS precision and detection limits, however turned out to be compromised by procedural blanks. The full analytical performance of the ICP-MS-based immunoassay proposed was assessed for detection of transferrin (Tf), present at the low ng mL{sup −1} range in a complex “model” synthetic matrix, where the total protein

  15. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

    Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

    2016-01-01

    The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of

  16. Planar reorientation maneuvers of space multibody systems using internal controls

    Reyhanoglu, Mahmut; Mcclamroch, N. H.

    1992-01-01

    In this paper a reorientation maneuvering strategy for an interconnection of planar rigid bodies in space is developed. It is assumed that there are no exogeneous torques, and torques generated by joint motors are used as means of control so that the total angular momentum of the multibody system is a constant, assumed to be zero in this paper. The maneuver strategy uses the nonintegrability of the expression for the angular momentum. We demonstrate that large-angle maneuvers can be designed to achieve an arbitrary reorientation of the multibody system with respect to an inertial frame. The theoretical background for carrying out the required maneuvers is briefly summarized. Specifications and computer simulations of a specific reorientation maneuver, and the corresponding control strategies, are described.

  17. Forward-backward multiplicity correlations of target fragments in nucleus-emulsion collisions at a few hundred MeV/u

    Zhang Donghai; Chen Yanling; Wang Guorong; Li Wangdong; Wang Qing; Yao Jijie; Zhou Jianguo; Li Rong; Li Junsheng; Li Huiling

    2015-01-01

    The forward-backward multiplicity and correlations of a target evaporated fragment (black track particle) and target recoiled proton (grey track particle) emitted from 150 A MeV "4He, 290 A MeV "1"2C, 400 A MeV "1"2C, 400 A MeV "2"0Ne and 500 A MeV "5"6Fe induced different types of nuclear emulsion target interactions are investigated. It is found that the forward and backward averaged multiplicity of a grey, black and heavily ionized track particle increases with the increase of the target size. The averaged multiplicity of a forward black track particle, backward black track particle, and backward grey track particle do not depend on the projectile size and energy, but the averaged multiplicity of a forward grey track particle increases with an increase of projectile size and energy. The backward grey track particle multiplicity distribution follows an exponential decay law and the decay constant decreases with an increase of target size. The backward-forward multiplicity correlations follow linear law which is independent of the projectile size and energy, and the saturation effect is observed in some heavy target data sets. (authors)

  18. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma.

    Crawford, Lisa J; Anderson, Gordon; Johnston, Cliona K; Irvine, Alexandra E

    2016-10-25

    Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIα (TOPIIα) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIα levels were first increased through pre-treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM.

  19. COMPARATIVE EVALUATION OF FILTERS USED IN TRACKING AIR TARGETS

    Y. I. Strekalovskaya

    2015-01-01

    Full Text Available Using an imitation model for a flow of heterogeneous air targets the comparative assessment of the αβ, αβγ and the Kalman filters efficiency is evaluated. In the case of slightly maneuvering target the difference in filters’ efficiency is statistically insignificant; in the case of sharp maneuvering the Kalman filter is significantly more precise.

  20. AIRCRAFT CONFLICTS RESOLUTION BY COURSE MANEUVERING

    В. Харченко

    2011-02-01

    Full Text Available Enhancement of requirements for air traffic efficiency at increasing of flights intensity determines the necessity of development of new optimization methods for aircraft conflict resolutions. The statement of problem of optimal conflict resolutions at Cooperative Air Traffic Management was done. The method for optimal aircraft conflict  resolution by course maneuvering has been  developed. The method using dynamic programming provides planning of aircraft conflict-free trajectory with minimum length. The decomposition of conflict resolution process on phases and stages, definition of states, controls and recursive  equations for generation of optimal course control program were done. Computer modeling of aircraft conflict resolution by developed method was done

  1. Analysis of ship maneuvering data from simulators

    Frette, V.; Kleppe, G.; Christensen, K.

    2011-03-01

    We analyze complex manuevering histories of ships obtained from training sessions on bridge simulators. Advanced ships are used in fields like offshore oil exploration: dive support vessels, supply vessels, anchor handling vessels, tugs, cable layers, and multi-purpose vessels. Due to high demands from the operations carried out, these ships need to have very high maneuverability. This is achieved through a propulsion system with several thrusters, water jets, and rudders in addition to standard propellers. For some operations, like subsea maintenance, it is crucial that the ship accurately keeps a fixed position. Therefore, bridge systems usually incorporate equipment for Dynamic Positioning (DP). DP is a method to keep ships and semi submersible rigs in a fixed position using the propulsion systems instead of anchors. It may also be used for sailing a vessel from one position to another along a predefined route. Like an autopilot on an airplane, DP may operate without human involvement. The method relies on accurate determination of position from external reference systems like GPS, as well as a continuously adjusted mathematical model of the ship and external forces from wind, waves and currents. In a specific simulator exercise for offshore crews, a ship is to be taken up to an installation consisting of three nearby oil platforms connected by bridges (Frigg field, North Sea), where a subsea inspection is to be carried out. Due to the many degrees of freedom during maneuvering, including partly or full use of DP, the chosen routes vary significantly. In this poster we report preliminary results on representations of the complex maneuvering histories; representations that allow comparison between crew groups, and, possibly, sorting of the different strategic choices behind.

  2. Contingency Trajectory Design for a Lunar Orbit Insertion Maneuver Failure by the Lunar Atmosphere Dust Environment Explorer (LADEE) Spacecraft

    Genova, Anthony L.; Loucks, Michael; Carrico, John

    2014-01-01

    The purpose of this extended abstract is to present results from a failed lunar-orbit insertion (LOI) maneuver contingency analysis for the Lunar Atmosphere Dust Environment Explorer (LADEE) mission, managed and operated by NASA Ames Research Center in Moffett Field, CA. The LADEE spacecrafts nominal trajectory implemented multiple sub-lunar phasing orbits centered at Earth before eventually reaching the Moon (Fig. 1) where a critical LOI maneuver was to be performed [1,2,3]. If this LOI was missed, the LADEE spacecraft would be on an Earth-escape trajectory, bound for heliocentric space. Although a partial mission recovery is possible from a heliocentric orbit (to be discussed in the full paper), it was found that an escape-prevention maneuver could be performed several days after a hypothetical LOI-miss, allowing a return to the desired science orbit around the Moon without leaving the Earths sphere-of-influence (SOI).

  3. Signal and data processing of small targets 1992; Proceedings of the Meeting, Orlando, FL, Apr. 20-22, 1992

    Drummond, Oliver E.

    This volume on signal and data processing of small targets contains chapters devoted to signal processing, low observable detection, systems and simulations, association and filtering in tracking, multiple sensor processing and fusion, and data processing. Papers included are on multisensor predetection fusion, adaptive whitening filters for small target detection, unified framework for IR target detection and tracking, and target detection from image sequences using pixel-based decision criterion. Attention is also given to automatic acquisition and tracking of rounds and targets for electrooptic fire control, advanced surveillance testbed and background modeling, an interacting-multiple-model algorithm for tracking targets that maneuver through coordinated turns, and angular momentum and ballistic tracking. Other papers are on a data integration (fusion) tree paradigm, single-scan tracking using N IR sensors, and track monitoring with single and multiple 2D passive sensors. (No individual items are abstracted in this volume)

  4. Enhanced Algorithms for EO/IR Electronic Stabilization, Clutter Suppression, and Track-Before-Detect for Multiple Low Observable Targets

    Tartakovsky, A.; Brown, A.; Brown, J.

    The paper describes the development and evaluation of a suite of advanced algorithms which provide significantly-improved capabilities for finding, fixing, and tracking multiple ballistic and flying low observable objects in highly stressing cluttered environments. The algorithms have been developed for use in satellite-based staring and scanning optical surveillance suites for applications including theatre and intercontinental ballistic missile early warning, trajectory prediction, and multi-sensor track handoff for midcourse discrimination and intercept. The functions performed by the algorithms include electronic sensor motion compensation providing sub-pixel stabilization (to 1/100 of a pixel), as well as advanced temporal-spatial clutter estimation and suppression to below sensor noise levels, followed by statistical background modeling and Bayesian multiple-target track-before-detect filtering. The multiple-target tracking is performed in physical world coordinates to allow for multi-sensor fusion, trajectory prediction, and intercept. Output of detected object cues and data visualization are also provided. The algorithms are designed to handle a wide variety of real-world challenges. Imaged scenes may be highly complex and infinitely varied -- the scene background may contain significant celestial, earth limb, or terrestrial clutter. For example, when viewing combined earth limb and terrestrial scenes, a combination of stationary and non-stationary clutter may be present, including cloud formations, varying atmospheric transmittance and reflectance of sunlight and other celestial light sources, aurora, glint off sea surfaces, and varied natural and man-made terrain features. The targets of interest may also appear to be dim, relative to the scene background, rendering much of the existing deployed software useless for optical target detection and tracking. Additionally, it may be necessary to detect and track a large number of objects in the threat cloud

  5. Lack of magnetic resonance imaging lesion activity as a treatment target in multiple sclerosis: An evaluation using electronically collected outcomes.

    Conway, Devon S; Thompson, Nicolas R; Cohen, Jeffrey A

    2016-09-01

    The appropriate treatment target in multiple sclerosis (MS) is unclear. Lack of magnetic resonance imaging (MRI) lesion activity, a component of the no evidence of disease activity concept, has been proposed as a treatment target in MS. We used our MS database to investigate whether aggressively pursuing MRI stability by changing disease modifying therapy (DMT) when MRI activity is observed leads to better clinical and imaging outcomes. The Knowledge Program (KP) is a database linked to our electronic medical record allowing capture of patient and clinician reported outcomes. Through KP query and chart review, we identified all relapsing-remitting MS patients visiting between 1 January 2008 and 31 December 2014 with active MRIs despite DMT. Propensity modeling based on demographic and disease characteristics was used to match DMT switchers to non-switchers. KP and MRI outcomes were compared 18 months after the active MRI using mixed-effects linear regression models. We identified 417 patients who met criteria for our analysis. After propensity matching, 78 switchers and 91 non-switchers were analyzed. There was no difference in clinical or radiologic outcomes between these groups at 18 months. We did not find a short-term benefit of changing DMT to pursue MRI stability. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

    Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-10-01

    In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Double ionization of the hydrogen sulfide molecule by electron impact: Influence of the target orientation on multiple differential cross sections

    Imadouchene, N. [Laboratoire de Mécanique, Structures et Energétique Université Mouloud Mammeri de Tizi-Ouzou, B.P. 17, Tizi-Ouzou 15000 (Algeria); Aouchiche, H., E-mail: h_aouchiche@yahoo.fr [Laboratoire de Mécanique, Structures et Energétique Université Mouloud Mammeri de Tizi-Ouzou, B.P. 17, Tizi-Ouzou 15000 (Algeria); Champion, C. [Centre d’Etudes Nucléaires de Bordeaux Gradignan, Université Bordeaux, CNRS/IN2P3, Boîte Postale 120, Gradignan 33175 (France)

    2016-07-15

    Highlights: • The double ionization of the H{sub 2}S molecule is here theoretically studied. • The orientation dependence of the differential cross sections is scrutinized. • The specific double ionizing mechanisms are clearly identified. - Abstract: Multiple differential cross sections of double ionization of hydrogen sulfide molecule impacted by electrons are here investigated within the first Born approximation. In the initial state, the incident electron is represented by a plane wave function whereas the target is described by means of a single-center molecular wave function. In the final state, the two ejected electrons are described by Coulomb wave functions coupled by the Gamow factor, whereas the scattered electron is described by a plane wave. In this work, we analyze the role played by the molecular target orientation in the double ionization of the four outermost orbitals, namely 2b{sub 1}, 5a{sub 1}, 2b{sub 2} and 4a{sub 1} in considering the particular case of two electrons ejected from the same orbital. The contribution of each final state to the double ionization process is studied in terms of shape and magnitude for specific molecular orientations and for each molecular orbital we identified the mechanisms involved in the double ionization process, namely, the Shake-Off and the Two-Step 1.

  8. The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis

    Knipe, Rachel S.; Tager, Andrew M.

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. PMID:25395505

  9. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice.

    Wang, Z; Gleichmann, H

    1998-01-01

    In mice, diabetes can be induced by multiple low doses of streptozotocin (MLD-STZ), i.e., 40 mg/kg body wt on each of 5 consecutive days. In this model, diabetes develops only when STZ induces both beta-cell toxicity and T-cell-dependent immune reactions. The target molecule(s) of MLD-STZ-induced beta-cell toxicity are not known, however. In this study, we report that GLUT2 is a target molecule for MLD-STZ toxicity. Ex vivo, a gradual decrement of both GLUT2 protein and mRNA expression was found in pancreatic islets isolated from MLD-STZ-treated C57BL/6 male mice, whereas mRNA expression of beta-actin, glucokinase, and proinsulin remained unaffected. Significant reduction of both GLUT2 protein and mRNA expression was first noted 1 day after the third STZ injection, clearly preceding the onset of hyperglycemia. The extent of reduction increased with the number of STZ injections administered and increased over time, after the last, i.e., fifth, STZ injection. The STZ-induced reduction of GLUT2 protein and mRNA was not due to an essential loss of beta-cells, because ex vivo, not only the total RNA yield and protein content in isolated islets, but also proinsulin mRNA expression, failed to differ significantly in the differently treated groups. Furthermore, islets isolated from MLD-STZ-treated donors responded to the nonglucose secretagogue arginine in a pattern similar to that of solvent-treated donors. Interestingly, the MLD-STZ-induced reduction of both GLUT2 protein and mRNA was prevented by preinjecting mice with 5-thio-D-glucose before each STZ injection. Apparently, GLUT2 is a crucial target molecule of MLD-STZ toxicity, and this toxicity seems to precede the immune reactions against beta-cells.

  10. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

  11. Ship maneuvering digital simulator; Simulador digital de manobras de navios

    Souza Junior, Jesse Rebello; Tannuri, Eduardo Aoun; Oshiro, Anderson Takehiro [Universidade de Sao Paulo (USP), SP (Brazil). Escola Politecnica. Dept. de Engenharia Naval e Oceanica

    2008-07-01

    This paper reports on two case studies making use of a digital simulator to investigate the maneuvering motions of ships in canals with shallow and restricted waters. The first case study corresponds to a maneuvering analysis conducted for the Port of Rio Grande (RS - Brazil), whose aim was to assess the potential impact upon maneuvers of the presence of a large offshore platform (the PETROBRAS P-53) which is to remain docked for several months at the Port to complete its construction. The second study made use of the simulator to evaluate the maneuvering conditions along the approach route and maneuvering basin of the Port of Ponta do Felix (PR - Brazil). The simulator includes a complete mathematical model of the ship dynamics in the horizontal plane when subjected to wind and current forces. It also comprises detailed models for the action of thrusters and propellers, both fixed and azimuth, employed to control maneuvers and dynamically position ships, as well as rudders and tugboats. He models used by the simulator allow for the effects of shallow and restricted waters, including the increase in resistance and lateral forces, increase in additional mass and the appearance of lateral and vertical suction (squatting). The simulator is implemented via an interactive interface through which the user is able to apply control actions (rudder angle, main engine, thrusters and tugboats) in real time during maneuvers, thereby reproducing to some extent the action of a pilot. (author)

  12. Helicopter Pilot Performance for Discrete-maneuver Flight Tasks

    Heffley, R. K.; Bourne, S. M.; Hindson, W. S.

    1984-01-01

    This paper describes a current study of several basic helicopter flight maneuvers. The data base consists of in-flight measurements from instrumented helicopters using experienced pilots. The analysis technique is simple enough to apply without automatic data processing, and the results can be used to build quantitative matah models of the flight task and some aspects of the pilot control strategy. In addition to describing the performance measurement technqiue, some results are presented which define the aggressiveness and amplitude of maneuvering for several lateral maneuvers including turns and sidesteps.

  13. Development of Strategy Generator for PWRs Core Maneuver

    Deswandri

    2003-01-01

    Generally, nuclear power plants are utilized for base-load operation. However, if the nuclear capacity constitutes a large fraction of the total electric capacity in a country, the ability of nuclear power plants to perform load following operation is inevitable. In the load following operation, the reactor power is adjusted based on the fluctuation of electric power demand in the grid. That changes of power level can cause unbalance in the reactor, therefore, the control actions should be done during the power maneuvering. In order that the control actions could be effective and efficient, guidance for the reactor operators is needed. Strategy generator refers to a tool which provides guidance for operators as to control actions to be taken. This work developed the strategy generator based on the three concepts of control strategy. By numerical simulation, performance of these three strategies was tested and compared. The simulation result shows the unique characteristic for each strategy and discussion was provided to evaluate the abilities of each strategy in achieving the control targets. (author)

  14. Managing multiple diffuse pressures on water quality and ecological habitat: Spatially targeting effective mitigation actions at the landscape scale.

    Joyce, Hannah; Reaney, Sim

    2015-04-01

    Catchment systems provide multiple benefits for society, including: land for agriculture, climate regulation and recreational space. Yet, these systems also have undesirable externalities, such as flooding, and the benefits they create can be compromised through societal use. For example, agriculture, forestry and urban land use practices can increase the export of fine sediment and faecal indicator organisms (FIO) delivered to river systems. These diffuse landscape pressures are coupled with pressures on the in stream temperature environment from projected climate change. Such pressures can have detrimental impacts on water quality and ecological habitat and consequently the benefits they provide for society. These diffuse and in-stream pressures can be reduced through actions at the landscape scale but are commonly tackled individually. Any intervention may have benefits for other pressures and hence the challenge is to consider all of the different pressures simultaneously to find solutions with high levels of cross-pressure benefits. This research presents (1) a simple but spatially distributed model to predict the pattern of multiple pressures at the landscape scale, and (2) a method for spatially targeting the optimum location for riparian woodland planting as mitigation action against these pressures. The model follows a minimal information requirement approach along the lines of SCIMAP (www.scimap.org.uk). This approach defines the critical source areas of fine sediment diffuse pollution, rapid overland flow and FIOs, based on the analysis of the pattern of the pressure in the landscape and the connectivity from source areas to rivers. River temperature was modeled using a simple energy balance equation; focusing on temperature of inflowing and outflowing water across a catchment. The model has been calibrated using a long term observed temperature record. The modelling outcomes enabled the identification of the severity of each pressure in relative rather

  15. Improvements to the adaptive maneuvering logic program

    Burgin, George H.

    1986-01-01

    The Adaptive Maneuvering Logic (AML) computer program simulates close-in, one-on-one air-to-air combat between two fighter aircraft. Three important improvements are described. First, the previously available versions of AML were examined for their suitability as a baseline program. The selected program was then revised to eliminate some programming bugs which were uncovered over the years. A listing of this baseline program is included. Second, the equations governing the motion of the aircraft were completely revised. This resulted in a model with substantially higher fidelity than the original equations of motion provided. It also completely eliminated the over-the-top problem, which occurred in the older versions when the AML-driven aircraft attempted a vertical or near vertical loop. Third, the requirements for a versatile generic, yet realistic, aircraft model were studied and implemented in the program. The report contains detailed tables which make the generic aircraft to be either a modern, high performance aircraft, an older high performance aircraft, or a previous generation jet fighter.

  16. Effects-Based Operations: The End of Dominant Maneuver?

    Cheek, Gary

    2002-01-01

    ... without dominant ground maneuver. The paper concludes that such thinking misreads a historical warfare lethality trend in a potentially dangerous effort to vindicate the Air Force doctrine of strategic attack...

  17. Close Proximity Robotic Maneuvering through Flux Pinning Manipulation

    National Aeronautics and Space Administration — Non-contacting actuation technology like flux pinning has never been demonstrated in space. The development of a nonphysical joint is critical for maneuvers such as...

  18. Automated Precision Maneuvering and Landing in Extreme and Constrained Environments

    National Aeronautics and Space Administration — Autonomous, precise maneuvering and landing in extreme and constrained environments is a key enabler for future NASA missions. Missions to map the interior of a...

  19. Tongue-Driven Wheelchair Out-Maneuvers the Competition

    ... 2, 2014 Tongue-Driven Wheelchair Out-Maneuvers the Competition Researchers funded by the National Institute of Biomedical ... significant step towards vastly improving the independence and quality of life of individuals with tetraplegia, and is ...

  20. Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

    Saha, Manujendra N; Jiang, Hua; Yang, Yijun; Zhu, Xiaoyun; Wang, Xiaoming; Schimmer, Aaron D; Qiu, Lugui; Chang, Hong

    2012-01-01

    The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK

  1. Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

    Manujendra N Saha

    Full Text Available The low frequency of p53 alterations e.g., mutations/deletions (∼10% in multiple myeloma (MM makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP analysis showed that activated c-Jun binds to the activator protein-1 (AP-1 binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with

  2. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

    Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

    2016-11-01

    Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Two (or three) is one too many: testing the flexibility of contextual cueing with multiple target locations.

    Zellin, Martina; Conci, Markus; von Mühlenen, Adrian; Müller, Hermann J

    2011-10-01

    Visual search for a target object is facilitated when the object is repeatedly presented within an invariant context of surrounding items ("contextual cueing"; Chun & Jiang, Cognitive Psychology, 36, 28-71, 1998). The present study investigated whether such invariant contexts can cue more than one target location. In a series of three experiments, we showed that contextual cueing is significantly reduced when invariant contexts are paired with two rather than one possible target location, whereas no contextual cueing occurs with three distinct target locations. Closer data inspection revealed that one "dominant" target always exhibited substantially more contextual cueing than did the other, "minor" target(s), which caused negative contextual-cueing effects. However, minor targets could benefit from the invariant context when they were spatially close to the dominant target. In sum, our experiments suggest that contextual cueing can guide visual attention to a spatially limited region of the display, only enhancing the detection of targets presented inside that region.

  4. Multiple reaction monitoring targeted LC-MS analysis of potential cell death marker proteins for increased bioprocess control.

    Albrecht, Simone; Kaisermayer, Christian; Reinhart, David; Ambrose, Monica; Kunert, Renate; Lindeberg, Anna; Bones, Jonathan

    2018-05-01

    The monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. A representative set of six proteins, namely GPDH, PRDX1, LGALS1, CFL1, TAGLN2 and MDH, which were identified in a previous CHO-K1 cell death model using discovery LC-MS E was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM-MS) platform and verified. The universality of the markers was confirmed in a cell growth model for which three Chinese hamster ovary host cell lines (CHO-K1, CHO-S, CHO-DG44) were grown in batch culture in two different types of basal media. LC-MRM-MS was also applied to spent media (n = 39) from four perfusion biomanufacturing series. Stable isotope-labelled peptide analogues and a stable isotope-labelled monoclonal antibody were used for improved protein quantitation and simultaneous monitoring of the workflow reproducibility. Significant increases in protein concentrations were observed for all viability marker proteins upon increased dead cell numbers and allowed for discrimination of spent media with dead cell densities below and above 1 × 10 6  dead cells/mL which highlights the potential of the selected viability marker proteins in bioprocess control. Graphical abstract Overview of the LC-MRM-MS workflow for the determination of proteomic markers in conditioned media from the bioreactor that correlate with CHO cell death.

  5. Models and Algorithms for Tracking Target with Coordinated Turn Motion

    Xianghui Yuan

    2014-01-01

    Full Text Available Tracking target with coordinated turn (CT motion is highly dependent on the models and algorithms. First, the widely used models are compared in this paper—coordinated turn (CT model with known turn rate, augmented coordinated turn (ACT model with Cartesian velocity, ACT model with polar velocity, CT model using a kinematic constraint, and maneuver centered circular motion model. Then, in the single model tracking framework, the tracking algorithms for the last four models are compared and the suggestions on the choice of models for different practical target tracking problems are given. Finally, in the multiple models (MM framework, the algorithm based on expectation maximization (EM algorithm is derived, including both the batch form and the recursive form. Compared with the widely used interacting multiple model (IMM algorithm, the EM algorithm shows its effectiveness.

  6. D- production by multiple charge-transfer collisions in metal-vapor targets. [1 to 50 keV D/sup +/

    Schlachter, A.S.

    1977-09-01

    A beam of D/sup -/ions can be produced by multiple charge-transfer collisions of a D/sup +/ beam in a thick metal-vapor target. Cross sections and equilibrium charge-state fractions are presented and discussed.

  7. Technical Note: Using k-means clustering to determine the number and position of isocenters in MLC-based multiple target intracranial radiosurgery.

    Yock, Adam D; Kim, Gwe-Ya

    2017-09-01

    To present the k-means clustering algorithm as a tool to address treatment planning considerations characteristic of stereotactic radiosurgery using a single isocenter for multiple targets. For 30 patients treated with stereotactic radiosurgery for multiple brain metastases, the geometric centroids and radii of each met were determined from the treatment planning system. In-house software used this as well as weighted and unweighted versions of the k-means clustering algorithm to group the targets to be treated with a single isocenter, and to position each isocenter. The algorithm results were evaluated using within-cluster sum of squares as well as a minimum target coverage metric that considered the effect of target size. Both versions of the algorithm were applied to an example patient to demonstrate the prospective determination of the appropriate number and location of isocenters. Both weighted and unweighted versions of the k-means algorithm were applied successfully to determine the number and position of isocenters. Comparing the two, both the within-cluster sum of squares metric and the minimum target coverage metric resulting from the unweighted version were less than those from the weighted version. The average magnitudes of the differences were small (-0.2 cm 2 and 0.1% for the within cluster sum of squares and minimum target coverage, respectively) but statistically significant (Wilcoxon signed-rank test, P k-means clustering algorithm represented an advantage of the unweighted version for the within-cluster sum of squares metric, and an advantage of the weighted version for the minimum target coverage metric. While additional treatment planning considerations have a large influence on the final treatment plan quality, both versions of the k-means algorithm provide automatic, consistent, quantitative, and objective solutions to the tasks associated with SRS treatment planning using a single isocenter for multiple targets. © 2017 The Authors. Journal

  8. Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3.

    Ma, Jing; Gong, Wei; Liu, Su; Li, Qian; Guo, Mengzheng; Wang, Jinhan; Wang, Suying; Chen, Naiyao; Wang, Yafei; Liu, Qiang; Zhao, Hui

    2018-01-01

    The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

  9. Optimal starting conditions for the rendezvous maneuver: Analytical and computational approach

    Ciarcia, Marco

    The three-dimensional rendezvous between two spacecraft is considered: a target spacecraft on a circular orbit around the Earth and a chaser spacecraft initially on some elliptical orbit yet to be determined. The chaser spacecraft has variable mass, limited thrust, and its trajectory is governed by three controls, one determining the thrust magnitude and two determining the thrust direction. We seek the time history of the controls in such a way that the propellant mass required to execute the rendezvous maneuver is minimized. Two cases are considered: (i) time-to-rendezvous free and (ii) time-to-rendezvous given, respectively equivalent to (i) free angular travel and (ii) fixed angular travel for the target spacecraft. The above problem has been studied by several authors under the assumption that the initial separation coordinates and the initial separation velocities are given, hence known initial conditions for the chaser spacecraft. In this paper, it is assumed that both the initial separation coordinates and initial separation velocities are free except for the requirement that the initial chaser-to-target distance is given so as to prevent the occurrence of trivial solutions. Two approaches are employed: optimal control formulation (Part A) and mathematical programming formulation (Part B). In Part A, analyses are performed with the multiple-subarc sequential gradient-restoration algorithm for optimal control problems. They show that the fuel-optimal trajectory is zero-bang, namely it is characterized by two subarcs: a long coasting zero-thrust subarc followed by a short powered max-thrust braking subarc. While the thrust direction of the powered subarc is continuously variable for the optimal trajectory, its replacement with a constant (yet optimized) thrust direction produces a very efficient guidance trajectory. Indeed, for all values of the initial distance, the fuel required by the guidance trajectory is within less than one percent of the fuel required

  10. Manned maneuvering unit applications for automated rendezvous and capture

    Brehm, Donald L.; Cuseo, John A.; Lenda, Joseph A.; Ray, Lex; Whitsett, C. Edward

    Automated Rendezvous and Capture (AR&C) is an important technology to multiple National Aeronautics and Space Administration (NASA) programs and centers. The recent Johnson Spacecraft Center (JSC) AR&C Quality Function Deployment (QFD) has listed on-orbit demonstration of related technologies as a near term priority. Martin Marietta has been evaluating use of the Manned Maneuvering Unit (MMU) for a low cost near term on-orbit demonstration of AR&C technologies such as control algorithms, sensors, and processors as well as system level performance. The MMU Program began in 1979 as the method of repairing the Space Shuttle (STS) Thermal Protection System (the tiles). The units were not needed for this task, but were successfully employed during three Shuttle flights in 1984: a test flight was flown in in February as proof of concept, in April the MMU participated in the Solar Max Repair Mission, and in November the MMU's returned to space to successfully rescue the two errant satellites, Westar and Palapa. In the intervening years, the MMU simulator and MMU Qualification Test Unit (QTU) have been used for Astronaut training and experimental evaluations. The Extra-Vehicular Activities (EVA) Retriever has used the QTU, in an unmanned form, as a free-flyer on the Johnson Space Center (JSC) Precision Air Bearing Floor (PABF). Currently, the MMU is undergoing recertification for flight. The two flight units were removed from storage in September, 1991 and evaluation tests were performed. The tests demonstrated that the units are in good shape with no discrepancies that would preclude further use. The Return to Flight effort is currently clearing up recertification issues and evaluating the design against the present Shuttle environments.

  11. Exploring precrash maneuvers using classification trees and random forests.

    Harb, Rami; Yan, Xuedong; Radwan, Essam; Su, Xiaogang

    2009-01-01

    Taking evasive actions vis-à-vis critical traffic situations impending to motor vehicle crashes endows drivers an opportunity to avoid the crash occurrence or at least diminish its severity. This study explores the drivers, vehicles, and environments' characteristics associated with crash avoidance maneuvers (i.e., evasive actions or no evasive actions). Rear-end collisions, head-on collisions, and angle collisions are analyzed separately using decision trees and the significance of the variables on the binary response variable (evasive actions or no evasive actions) is determined. Moreover, the random forests method is employed to rank the importance of the drivers/vehicles/environments characteristics on crash avoidance maneuvers. According to the exploratory analyses' results, drivers' visibility obstruction, drivers' physical impairment, drivers' distraction are associated with crash avoidance maneuvers in all three types of accidents. Moreover, speed limit is associated with rear-end collisions' avoidance maneuvers and vehicle type is correlated with head-on collisions and angle collisions' avoidance maneuvers. It is recommended that future research investigates further the explored trends (e.g., physically impaired drivers, visibility obstruction) using driving simulators which may help in legislative initiatives and in-vehicle technology recommendations.

  12. Dynamic cerebral autoregulation changes during sub-maximal handgrip maneuver.

    Ricardo C Nogueira

    Full Text Available PURPOSE: We investigated the effect of handgrip (HG maneuver on time-varying estimates of dynamic cerebral autoregulation (CA using the autoregressive moving average technique. METHODS: Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO₂ pressure (PETCO₂, and noninvasive arterial blood pressure (ABP were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP, resistance area-product (RAP, and time-varying autoregulation index (ARI were obtained. RESULTS: PETCO₂ did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005, which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. CONCLUSION: Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism.

  13. Dynamic Cerebral Autoregulation Changes during Sub-Maximal Handgrip Maneuver

    Nogueira, Ricardo C.; Bor-Seng-Shu, Edson; Santos, Marcelo R.; Negrão, Carlos E.; Teixeira, Manoel J.; Panerai, Ronney B.

    2013-01-01

    Purpose We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving average technique. Methods Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying autoregulation index (ARI) were obtained. Results PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Conclusion Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism. PMID:23967113

  14. Investigation of piloting aids for manual control of hypersonic maneuvers

    Raney, David L.; Phillips, Michael R.; Person, Lee H., Jr.

    1995-01-01

    An investigation of piloting aids designed to provide precise maneuver control for an air-breathing hypersonic vehicle is described. Stringent constraints and nonintuitive high-speed flight effects associated with maneuvering in the hypersonic regime raise the question of whether manual control of such a vehicle should even be considered. The objectives of this research were to determine the extent of manual control that is desirable for a vehicle maneuvering in this regime and to identify the form of aids that must be supplied to the pilot to make such control feasible. A piloted real-time motion-based simulation of a hypersonic vehicle concept was used for this study, and the investigation focused on a single representative cruise turn maneuver. Piloting aids, which consisted of an auto throttle, throttle director, autopilot, flight director, and two head-up display configurations, were developed and evaluated. Two longitudinal control response types consisting of a rate-command/attitude-hold system and a load factor-rate/load-factor-hold system were also compared. The complete set of piloting aids, which consisted of the autothrottle, throttle director, and flight director, improved the average Cooper-Harper flying qualities ratings from 8 to 2.6, even though identical inner-loop stability and control augmentation was provided in all cases. The flight director was determined to be the most critical of these aids, and the cruise turn maneuver was unachievable to adequate performance specifications in the absence of this flight director.

  15. Feature-space assessment of electrical impedance tomography coregistered with computed tomography in detecting multiple contrast targets

    Krishnan, Kalpagam; Liu, Jeff; Kohli, Kirpal

    2014-01-01

    Purpose: Fusion of electrical impedance tomography (EIT) with computed tomography (CT) can be useful as a clinical tool for providing additional physiological information about tissues, but requires suitable fusion algorithms and validation procedures. This work explores the feasibility of fusing EIT and CT images using an algorithm for coregistration. The imaging performance is validated through feature space assessment on phantom contrast targets. Methods: EIT data were acquired by scanning a phantom using a circuit, configured for injecting current through 16 electrodes, placed around the phantom. A conductivity image of the phantom was obtained from the data using electrical impedance and diffuse optical tomography reconstruction software (EIDORS). A CT image of the phantom was also acquired. The EIT and CT images were fused using a region of interest (ROI) coregistration fusion algorithm. Phantom imaging experiments were carried out on objects of different contrasts, sizes, and positions. The conductive medium of the phantoms was made of a tissue-mimicking bolus material that is routinely used in clinical radiation therapy settings. To validate the imaging performance in detecting different contrasts, the ROI of the phantom was filled with distilled water and normal saline. Spatially separated cylindrical objects of different sizes were used for validating the imaging performance in multiple target detection. Analyses of the CT, EIT and the EIT/CT phantom images were carried out based on the variations of contrast, correlation, energy, and homogeneity, using a gray level co-occurrence matrix (GLCM). A reference image of the phantom was simulated using EIDORS, and the performances of the CT and EIT imaging systems were evaluated and compared against the performance of the EIT/CT system using various feature metrics, detectability, and structural similarity index measures. Results: In detecting distilled and normal saline water in bolus medium, EIT as a stand

  16. Targeting Accuracy of Image-Guided Radiosurgery for Intracranial Lesions: A Comparison Across Multiple Linear Accelerator Platforms.

    Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Brown, Stephen; Gordon, James; Wen, Ning

    2016-04-01

    To evaluate the overall positioning accuracy of image-guided intracranial radiosurgery across multiple linear accelerator platforms. A computed tomography scan with a slice thickness of 1.0 mm was acquired of an anthropomorphic head phantom in a BrainLAB U-frame mask. The phantom was embedded with three 5-mm diameter tungsten ball bearings, simulating a central, a left, and an anterior cranial lesion. The ball bearings were positioned to radiation isocenter under ExacTrac X-ray or cone-beam computed tomography image guidance on 3 Linacs: (1) ExacTrac X-ray localization on a Novalis Tx; (2) cone-beam computed tomography localization on the Novalis Tx; (3) cone-beam computed tomography localization on a TrueBeam; and (4) cone-beam computed tomography localization on an Edge. Each ball bearing was positioned 5 times to the radiation isocenter with different initial setup error following the 4 image guidance procedures on the 3 Linacs, and the mean (µ) and one standard deviation (σ) of the residual error were compared. Averaged overall 3 ball bearing locations, the vector length of the residual setup error in mm (µ ± σ) was 0.6 ± 0.2, 1.0 ± 0.5, 0.2 ± 0.1, and 0.3 ± 0.1 on ExacTrac X-ray localization on a Novalis Tx, cone-beam computed tomography localization on the Novalis Tx, cone-beam computed tomography localization on a TrueBeam, and cone-beam computed tomography localization on an Edge, with their range in mm being 0.4 to 1.1, 0.4 to 1.9, 0.1 to 0.5, and 0.2 to 0.6, respectively. The congruence between imaging and radiation isocenters in mm was 0.6 ± 0.1, 0.7 ± 0.1, 0.3 ± 0.1, and 0.2 ± 0.1, for the 4 systems, respectively. Targeting accuracy comparable to frame-based stereotactic radiosurgery can be achieved with image-guided intracranial stereotactic radiosurgery treatment. © The Author(s) 2015.

  17. On spacecraft maneuvers control subject to propellant engine modes.

    Mazinan, A H

    2015-09-01

    The paper attempts to address a new control approach to spacecraft maneuvers based upon the modes of propellant engine. A realization of control strategy is now presented in engine on mode (high thrusts as well as further low thrusts), which is related to small angle maneuvers and engine off mode (specified low thrusts), which is also related to large angle maneuvers. There is currently a coarse-fine tuning in engine on mode. It is shown that the process of handling the angular velocities are finalized via rate feedback system in engine modes, where the angular rotations are controlled through quaternion based control (QBCL)strategy in engine off mode and these ones are also controlled through an optimum PID (OPIDH) strategy in engine on mode. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  18. A Maneuvering Flight Noise Model for Helicopter Mission Planning

    Greenwood, Eric; Rau, Robert; May, Benjamin; Hobbs, Christopher

    2015-01-01

    A new model for estimating the noise radiation during maneuvering flight is developed in this paper. The model applies the Quasi-Static Acoustic Mapping (Q-SAM) method to a database of acoustic spheres generated using the Fundamental Rotorcraft Acoustics Modeling from Experiments (FRAME) technique. A method is developed to generate a realistic flight trajectory from a limited set of waypoints and is used to calculate the quasi-static operating condition and corresponding acoustic sphere for the vehicle throughout the maneuver. By using a previously computed database of acoustic spheres, the acoustic impact of proposed helicopter operations can be rapidly predicted for use in mission-planning. The resulting FRAME-QS model is applied to near-horizon noise measurements collected for the Bell 430 helicopter undergoing transient pitch up and roll maneuvers, with good agreement between the measured data and the FRAME-QS model.

  19. Two (or three) is one too many : testing the flexibility of contextual cueing with multiple target locations

    Zellin, Martina; Conci, Markus; von Mühlenen, Adrian; Müller, Hermann J.

    2011-01-01

    Visual search for a target object is facilitated when the object is repeatedly presented within an invariant context of surrounding items ("contextual cueing"; Chun & Jiang, Cognitive Psychology, 36, 28-71, 1998). The present study investigated whether such invariant contexts can cue more than one target location. In a series of three experiments, we showed that contextual cueing is significantly reduced when invariant contexts are paired with two rather than one possible target location, whe...

  20. Maneuver Planning for Conjunction Risk Mitigation with Ground-track Control Requirements

    McKinley, David

    2008-01-01

    The planning of conjunction Risk Mitigation Maneuvers (RMM) in the presence of ground-track control requirements is analyzed. Past RMM planning efforts on the Aqua, Aura, and Terra spacecraft have demonstrated that only small maneuvers are available when ground-track control requirements are maintained. Assuming small maneuvers, analytical expressions for the effect of a given maneuver on conjunction geometry are derived. The analytical expressions are used to generate a large trade space for initial RMM design. This trade space represents a significant improvement in initial maneuver planning over existing methods that employ high fidelity maneuver models and propagation.

  1. Design and Implementation of the Automated Rendezvous Targeting Algorithms for Orion

    DSouza, Christopher; Weeks, Michael

    2010-01-01

    The Orion vehicle will be designed to perform several rendezvous missions: rendezvous with the ISS in Low Earth Orbit (LEO), rendezvous with the EDS/Altair in LEO, a contingency rendezvous with the ascent stage of the Altair in Low Lunar Orbit (LLO) and a contingency rendezvous in LLO with the ascent and descent stage in the case of an aborted lunar landing. Therefore, it is not difficult to realize that each of these scenarios imposes different operational, timing, and performance constraints on the GNC system. To this end, a suite of on-board guidance and targeting algorithms have been designed to meet the requirement to perform the rendezvous independent of communications with the ground. This capability is particularly relevant for the lunar missions, some of which may occur on the far side of the moon. This paper will describe these algorithms which are designed to be structured and arranged in such a way so as to be flexible and able to safely perform a wide variety of rendezvous trajectories. The goal of the algorithms is not to merely fly one specific type of canned rendezvous profile. Conversely, it was designed from the start to be general enough such that any type of trajectory profile can be flown.(i.e. a coelliptic profile, a stable orbit rendezvous profile, and a expedited LLO rendezvous profile, etc) all using the same rendezvous suite of algorithms. Each of these profiles makes use of maneuver types which have been designed with dual goals of robustness and performance. They are designed to converge quickly under dispersed conditions and they are designed to perform many of the functions performed on the ground today. The targeting algorithms consist of a phasing maneuver (NC), an altitude adjust maneuver (NH), and plane change maneuver (NPC), a coelliptic maneuver (NSR), a Lambert targeted maneuver, and several multiple-burn targeted maneuvers which combine one of more of these algorithms. The derivation and implementation of each of these

  2. Lorazepam induces multiple disturbances in selective attention: attentional overload, decrement in target processing efficiency, and shifts in perceptual discrimination and response bias.

    Michael, George Andrew; Bacon, Elisabeth; Offerlin-Meyer, Isabelle

    2007-09-01

    There is a general consensus that benzodiazepines affect attentional processes, yet only few studies have tried to investigate these impairments in detail. The purpose of the present study was to investigate the effects of a single dose of Lorazepam on performance in a target cancellation task with important time constraints. We measured correct target detections and correct distractor rejections, misses and false positives. The results show that Lorazepam produces multiple kinds of shifts in performance, which suggests that it impairs multipLe processes: (a) the evolution of performance over time was not the same between the placebo and the Lorazepam groups, with the Lorazepam affecting performance quite early after the beginning of the test. This is suggestive of a depletion of attentional resources during sequential attentional processing; (b) Lorazepam affected differently target and distractor processing, with target detection being the most impaired; (c) misses were more frequent under Lorazepam than under placebo, but no such difference was observed as far as false positives were concerned. Signal detection analyses showed that Lorazepam (d) decreased perceptual discrimination, and (e) reliably increased response bias. Our results bring new insights on the multiple effects of Lorazepam on selective attention which, when combined, may have deleterious effects on human performance.

  3. Maneuver Acoustic Flight Test of the Bell 430 Helicopter

    Watts, Michael E.; Snider, Royce; Greenwood, Eric; Baden, Joel

    2012-01-01

    A cooperative flight test by NASA, Bell Helicopter and the U.S. Army to characterize the steady state acoustics and measure the maneuver noise of a Bell Helicopter 430 aircraft was accomplished. The test occurred during June/July, 2011 at Eglin Air Force Base, Florida. This test gathered a total of 410 data points over 10 test days and compiled an extensive data base of dynamic maneuver measurements. Three microphone configurations with up to 31 microphones in each configuration were used to acquire acoustic data. Aircraft data included DGPS, aircraft state and rotor state information. This paper provides an overview of the test.

  4. Space Objects Maneuvering Detection and Prediction via Inverse Reinforcement Learning

    Linares, R.; Furfaro, R.

    This paper determines the behavior of Space Objects (SOs) using inverse Reinforcement Learning (RL) to estimate the reward function that each SO is using for control. The approach discussed in this work can be used to analyze maneuvering of SOs from observational data. The inverse RL problem is solved using the Feature Matching approach. This approach determines the optimal reward function that a SO is using while maneuvering by assuming that the observed trajectories are optimal with respect to the SO's own reward function. This paper uses estimated orbital elements data to determine the behavior of SOs in a data-driven fashion.

  5. Virtual simulation of maneuvering captive tests for a surface vessel

    Ahmad Hajivand

    2015-09-01

    Full Text Available Hydrodynamic derivatives or coefficients are required to predict the maneuvering characteristics of a marine vehicle. These derivatives are obtained numerically for a DTMB 5512 model ship by virtual simulating of captive model tests in a CFD environment. The computed coefficients are applied to predict the turning circle and zigzag maneuvers of the model ship. The comparison of the simulated results with the available experimental data shows a very good agreement among them. The simulations show that the CFD is precise and affordable tool at the preliminary design stage to obtain maneuverability performance of a marine vehicles.

  6. The Evolution of Air-Sea Battle: How Army Attack/Reconnaissance Aviation Fits into the Joint Concept for Access and Maneuver in the Global Commons

    2016-05-13

    Joint targeting and maneuver. 3) The destruction of early warning systems and mobile missile launchers . A traditional use of Army Aviation would...provide targeting data. The PRC’s mobile missile launchers also add complexity to the Joint Force’s targeting challenge for MRBM, IRBM, and ASBMs...mobile missile launcher with inexpensive and plentiful 30 mm rounds. In a different threat environment, a more expensive and scarce Joint Direct

  7. 'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

    Nathali Kaushansky

    Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

  8. Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

    Yunfei Guo

    2012-04-01

    Full Text Available In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD called penalty DP-TBD (PDP-TBD is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

  9. Towards Semantic Understanding of Surrounding Vehicular Maneuvers

    Kristoffersen, Miklas Strøm; Dueholm, Jacob Velling; Satzoda, Ravi K.

    2016-01-01

    This paper proposes the use of multiple low-cost visual sensors to obtain a surround view of the ego-vehicle for semantic understanding. A multi-perspective view will assist the analysis of naturalistic driving studies (NDS), by automating the task of data reduction of the observed sequences...... into events. A user-centric vision-based framework is presented using a vehicle detector and tracker in each separate perspective. Multi-perspective trajectories are estimated and analyzed to extract 14 different events, including potential dangerous behaviors such as overtakes and cut-ins. The system...... is tested on ten sequences of real-world data collected on U. S. highways. The results show the potential use of multiple low-cost visual sensors for semantic understanding around the ego-vehicle....

  10. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants

    Lehto, Markku; Hynynen, Riikka; Karjalainen, Katja; Kuismanen, Esa; Hyvaerinen, Kati; Olkkonen, Vesa M.

    2005-01-01

    The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P 2 and PI(3,4,5)P 3 . A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of ORP3. The endoplasmic reticulum (ER) targeting of ORP3 is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of ORP3 with the ER and the nuclear membrane. Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3. Notably, over-expression of ORP3 together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid starvation promotes formation of dilated peripheral ER (DPER) structures dependent on the ORP3 protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of ORP3 in the membrane targeting of the protein

  11. Transient Structured Distance as a Maneuver in Marital Therapy

    Greene, Bernard L.; And Others

    1973-01-01

    Experience with 73 cases has shown the value of Transient Structured Distance as a maneuver in marriage therapy. While the TSD is a radical form of intervention with risks of anxiety reactions, homosexual panic, or divorce, it has proved effective with difficult forms of acute or chronic marital disharmony. (Author)

  12. 47 CFR 25.282 - Orbit raising maneuvers.

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Orbit raising maneuvers. 25.282 Section 25.282 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS... geostationary satellite orbit under this part is also authorized to transmit in connection with short-term...

  13. A Small State Maneuvering in the Changing World Order

    Sørensen, Camilla T. N.

    2016-01-01

    , especially the Danish approach to the BRICs, has developed in recent years, I show how Denmark – a small state – is trying to maneuver in the changing world order through a “creative agency” approach characterized by pragmatic low-profile activism. I develop a neoclassical realist framework and use...

  14. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  15. In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.

    Mahmoud ElHefnawi

    Full Text Available RNA interference (RNAi is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs targeting highly conserved regions of the hepatitis C virus (HCV genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258 were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h; they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic

  16. Multiplicities of charged pions and charged hadrons from deep-inelastic scattering of muons off an isoscalar target

    Adolph, C.; Aghasyan, M.; Akhunzyanov, R.; Alexeev, G. D.; Alexeev, M.; Amoroso, A.; Andrieux, V.; Anfimov, N. V.; Anosov, V.; Augsten, K.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.; Badelek, B.; Balestra, F.; Barth, J.; Beck, D.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E. R.; Birsa, R.; Bisplinghoff, J.; Bodlák, M.; Boer, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Büchele, M.; Capozza, L.; Chang, W.-C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chung, S.U.; Cicuttin, A.; Crespo, M.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S. S.; Dasgupta, S.; Denisov, O.; Dhara, L.; Donskov, S. V.; Doshita, N.; Duic, V.; Dünnweber, W.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Finger, M.; Finger jr., M.; Fischer, H.; Franco, C.; Fresne von Hohenesche, N.; Friedrich, J. M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O. P.; Gerassimov, S.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grabmüller, S.; Grasso, A.; Grosse-Perdekapm, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Haas, F.; Hahne, D.; von Harrach, D.; Hashimoto, R.; Heinsius, F. H.; Heitz, R.; Herrmann, E.; Hinterberger, F.; Horikawa, N.; d'Hose, N.; Hsieh, C.-Yu.; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jarý, V.; Joosten, R.; Jörg, P.; Kabuss, E.; Ketzer, B.; Khaustov, G. V.; Khokhlov, Yu. A.; Kisselev, Y.; Klein, F.; Klimaszewski, K.; Koivuniemi, J. H.; Kolosov, V. N.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V. F.; Kotzinian, A. M.; Kouznetsov, O.; Krämer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z. V.; Kuhn, R.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R. P.; Lednev, A. A.; Lehmann, A.; Levillain, M.; Levorato, S.; Lian, Y.-S.; Lichtenstadt, J.; Longo, R.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G. K.; Marchand, C.; Marianski, B.; Martin, A.; Marzec, J.; Matoušek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.; Meyer, M.; Meyer, W.; Michigami, T.; Mikhailov, Yu. V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Montuenga, P.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nikolaenko, V. I.; Nový, J.; Nowak, W. D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A. G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.-C.; Pereira, F.; Pešek, M.; Peshekhonov, D. V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V. A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Roskot, M.; Rossiyskaya, N. S.; Ryabchikov, D.; Rybnikov, A.; Rychter, A.; Salač, R.; Samoylenko, V. D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I. A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schönning, K.; Schopferer, S.; Seder, E.; Selyunin, A.; Shevchenko, O. Yu.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolík, J.; Sozzi, F.; Srnka, Aleš; Steffen, D.; Stolarski, M.; Šulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Tosello, F.; Tskhay, V.; Uhl, S.; Veloso, J.; Virius, M.; Vondra, J.; Weisrock, T.; Wilfert, M.; Windmolders, R.; Ter Wolbeek, J.; Zaremba, K.; Závada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Zhuravlev, N.; Ziembicki, M.; Zink, A.

    2017-01-01

    Roč. 764, JAN (2017), s. 1-10 ISSN 0370-2693 R&D Projects: GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : deep inelastic scattering * pion multiplicities * fragmentation functions Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Nuclear physics Impact factor: 4.807, year: 2016

  17. Target intervention against multiple-risk markers to reduce cardiovascular disease in patients with type 2 diabetes

    Gaede, Peter; Pedersen, Oluf

    2004-01-01

    The risk of cardiovascular disease is markedly increased in patients with type 2 diabetes with a prevalence twice as high compared to the background population. With the recognition of multiple concomitant risk factors for both microvascular as well as cardiovascular disease in type 2 diabetic pa...

  18. Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

    Kim SW

    2015-06-01

    Full Text Available Sang-Woo Kim, Dongwoo Khang Nanomedicine Laboratory, Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, South Korea Abstract: Over the past 60 years, numerous medical strategies have been employed to overcome neoplasms. In fact, with the exception of lung, bronchial, and pancreatic cancers, the 5-year survival rate of most cancers currently exceeds 70%. However, the quality of life of patients during chemotherapy remains unsatisfactory despite the increase in survival rate. The side effects of current chemotherapies stem from poor target efficiency at tumor sites due to the uncontrolled biodistribution of anticancer agents (ie, conventional or current approved nanodrugs. This review discusses the effective physiochemical factors for determining biodistribution of nanocarriers and, ultimately, increasing tumor-targeting probability by avoiding the reticuloendothelial system. Second, stem cell-conjugated nanotherapeutics was addressed to maximize the tumor searching ability and to inhibit tumor growth. Lastly, physicochemical material properties of anticancer nanodrugs were discussed for targeting cellular organelles with modulation of drug-release time. A better understanding of suggested topics will increase the tumor-targeting ability of anticancer drugs and, ultimately, promote the quality of life of cancer patients during chemotherapy. Keywords: cancer, anticancer nanodrugs, mesenchymal stem cell, intracellular trafficking

  19. Associating crash avoidance maneuvers with driver attributes and accident characteristics: a mixed logit model approach.

    Kaplan, Sigal; Prato, Carlo Giacomo

    2012-01-01

    The current study focuses on the propensity of drivers to engage in crash avoidance maneuvers in relation to driver attributes, critical events, crash characteristics, vehicles involved, road characteristics, and environmental conditions. The importance of avoidance maneuvers derives from the key role of proactive and state-aware road users within the concept of sustainable safety systems, as well as from the key role of effective corrective maneuvers in the success of automated in-vehicle warning and driver assistance systems. The analysis is conducted by means of a mixed logit model that represents the selection among 5 emergency lateral and speed control maneuvers (i.e., "no avoidance maneuvers," "braking," "steering," "braking and steering," and "other maneuvers) while accommodating correlations across maneuvers and heteroscedasticity. Data for the analysis were retrieved from the General Estimates System (GES) crash database for the year 2009 by considering drivers for which crash avoidance maneuvers are known. The results show that (1) the nature of the critical event that made the crash imminent greatly influences the choice of crash avoidance maneuvers, (2) women and elderly have a relatively lower propensity to conduct crash avoidance maneuvers, (3) drowsiness and fatigue have a greater negative marginal effect on the tendency to engage in crash avoidance maneuvers than alcohol and drug consumption, (4) difficult road conditions increase the propensity to perform crash avoidance maneuvers, and (5) visual obstruction and artificial illumination decrease the probability to carry out crash avoidance maneuvers. The results emphasize the need for public awareness campaigns to promote safe driving style for senior drivers and warning about the risks of driving under fatigue and distraction being comparable to the risks of driving under the influence of alcohol and drugs. Moreover, the results suggest the need to educate drivers about hazard perception, designing

  20. Myosin-1A Targets to Microvilli Using Multiple Membrane Binding Motifs in the Tail Homology 1 (TH1) Domain*

    Mazerik, Jessica N.; Tyska, Matthew J.

    2012-01-01

    One of the most abundant components of the enterocyte brush border is the actin-based monomeric motor, myosin-1a (Myo1a). Within brush border microvilli, Myo1a carries out a number of critical functions at the interface between membrane and actin cytoskeleton. Proper physiological function of Myo1a depends on its ability to bind to microvillar membrane, an interaction mediated by a C-terminal tail homology 1 (TH1) domain. However, little is known about the mechanistic details of the Myo1a-TH1/membrane interaction. Structure-function analysis of Myo1a-TH1 targeting in epithelial cells revealed that an N-terminal motif conserved among class I myosins and a C-terminal motif unique to Myo1a-TH1 are both required for steady state microvillar enrichment. Purified Myo1a bound to liposomes composed of phosphatidylserine and phosphoinositol 4,5-bisphosphate, with moderate affinity in a charge-dependent manner. Additionally, peptides of the N- and C-terminal regions required for targeting were able to compete with Myo1a for binding to highly charged liposomes in vitro. Single molecule total internal reflection fluorescence microscopy showed that these motifs are also necessary for slowing the membrane detachment rate in cells. Finally, Myo1a-TH1 co-localized with both lactadherin-C2 (a phosphatidylserine-binding protein) and PLCδ1-PH (a phosphoinositol 4,5-bisphosphate-binding protein) in microvilli, but only lactaderin-C2 expression reduced brush border targeting of Myo1a-TH1. Together, our results suggest that Myo1a targeting to microvilli is driven by membrane binding potential that is distributed throughout TH1 rather than localized to a single motif. These data highlight the diversity of mechanisms that enable different class I myosins to target membranes in distinct biological contexts. PMID:22367206

  1. A Sampling Based Approach to Spacecraft Autonomous Maneuvering with Safety Specifications

    Starek, Joseph A.; Barbee, Brent W.; Pavone, Marco

    2015-01-01

    This paper presents a methods for safe spacecraft autonomous maneuvering that leverages robotic motion-planning techniques to spacecraft control. Specifically the scenario we consider is an in-plan rendezvous of a chaser spacecraft in proximity to a target spacecraft at the origin of the Clohessy Wiltshire Hill frame. The trajectory for the chaser spacecraft is generated in a receding horizon fashion by executing a sampling based robotic motion planning algorithm name Fast Marching Trees (FMT) which efficiently grows a tree of trajectories over a set of probabillistically drawn samples in the state space. To enforce safety the tree is only grown over actively safe samples for which there exists a one-burn collision avoidance maneuver that circularizes the spacecraft orbit along a collision-free coasting arc and that can be executed under potential thrusters failures. The overall approach establishes a provably correct framework for the systematic encoding of safety specifications into the spacecraft trajectory generations process and appears amenable to real time implementation on orbit. Simulation results are presented for a two-fault tolerant spacecraft during autonomous approach to a single client in Low Earth Orbit.

  2. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

  3. The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts

    Eskildsen, Tilde V; Schneider, Mikael; Sandberg, Maria B

    2015-01-01

    INTRODUCTION: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular...... in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. RESULTS: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors...... pathways that fine-tuned by miR-132/212, suggesting a role for this miRNA family as master signalling switches in cardiac fibroblasts. Our data underscore the potential for miRNA tools to manipulate a large array of molecules and thereby control biological function....

  4. Selected Arterial Infusion Chemotherapy Combined with Target Drugs 
for Non-small Cell Lung Cancer with Multiple Brain Metastase

    Jinduo LI

    2012-05-01

    Full Text Available Background and objective The aim of this study is to evaluate the efficacy of selected arterial infusion chemotherapy in treating non-small cell lung cancer (NSCLC with multiple brain metastases and corresponding factors to influencing prognosis. Methods From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3 received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs. Interventional treatment was performed every four weeks, two-six cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or icotinib. Follow-up CT and MRI were regularly finished at interval of four weeks after two cycles of interventional treatment were finished or during taking targeted drugs in order to evaluate efficacy of the therapy. The procedure was stopped for the tumor disease was worse or the patient could not tolerate the toxity of drugs any longer. Results 31 patients was performed two to six cycles of interventional therapy, 3cycles at average. Response assessment showed that 5 (16.1% patients got a complete response (CR, 7 (22.6% had a partial response (PR, 11 (35.5% had a stable disease (SD and 8 (25.8% had a progressive disease (PD. The objective response rate (ORR was 38.7%, and the disease control rate was 74.2%. The median progression free survival (PFS and overall survival (OS were 13.1 months and 15.1 months. The 6-month survival rate, one-year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%, respectively. The patients’ OS and PFS were influenced by smoking state, tumor pathology, extracranial metastases, period of targeted drug taking and performance status, not by sex, age, before therapy and the total of brain metastases. Conclusion Selected arterial infusion chemotherapy with targeted drugs is one of the most effective and safe treatment to NSCLC with multiple brain metastases. Smoking status, tumor

  5. Evasive Maneuvers in Space Debris Environment and Technological Parameters

    Antônio D. C. Jesus

    2012-01-01

    Full Text Available We present a study of collisional dynamics between space debris and an operational vehicle in LEO. We adopted an approach based on the relative dynamics between the objects on a collisional course and with a short warning time and established a semianalytical solution for the final trajectories of these objects. Our results show that there are angular ranges in 3D, in addition to the initial conditions, that favor the collisions. These results allowed the investigation of a range of technological parameters for the spacecraft (e.g., fuel reserve that allow a safe evasive maneuver (e.g., time available for the maneuver. The numerical model was tested for different values of the impact velocity and relative distance between the approaching objects.

  6. Thermally-Constrained Fuel-Optimal ISS Maneuvers

    Bhatt, Sagar; Svecz, Andrew; Alaniz, Abran; Jang, Jiann-Woei; Nguyen, Louis; Spanos, Pol

    2015-01-01

    Optimal Propellant Maneuvers (OPMs) are now being used to rotate the International Space Station (ISS) and have saved hundreds of kilograms of propellant over the last two years. The savings are achieved by commanding the ISS to follow a pre-planned attitude trajectory optimized to take advantage of environmental torques. The trajectory is obtained by solving an optimal control problem. Prior to use on orbit, OPM trajectories are screened to ensure a static sun vector (SSV) does not occur during the maneuver. The SSV is an indicator that the ISS hardware temperatures may exceed thermal limits, causing damage to the components. In this paper, thermally-constrained fuel-optimal trajectories are presented that avoid an SSV and can be used throughout the year while still reducing propellant consumption significantly.

  7. Parametric Dependence of Initial LEV Behavior on Maneuvering Wings

    Berdon, Randall; Wabick, Kevin; Buchholz, James; Johnson, Kyle; Thurow, Brian; University of Iowa Team; Auburn University Team

    2017-11-01

    A maneuvering rectangular wing of aspect ratio 2 is examined experimentally using dye visualization and PIV to characterize the initial development of the leading-edge vortex (LEV) during a rolling maneuver in a uniform free stream. Understanding the underlying physics during the early evolution of the vortex is important for developing strategies to manipulate vortex evolution. Varying the dimensionless radius of gyration of the wing (Rg/c, where Rg is the radius of gyration and c is the chord) and the advance ratio (J=U/ ΩRg, where U is the free-stream velocity and Ω is the roll rate) affects the structure of the vortex and its propensity to remain attached. The influence of these parameters will be discussed, toward identification of similarity parameters governing vortex development. This work is supported by the Air Force Office of Scientific Research (Grant Number FA9550-16-1-0107, Dr. Douglas Smith, program manager).

  8. An expert system for pressurized water reactor load maneuvers

    Chaung Lin; Jungping Chen; Yihjiunn Lin; Lianshin Lin

    1993-01-01

    Restartup after reactor shutdown and load-follow operations are the important tasks in operating pressurized water reactors. Generally, the most efficient method is to apply constant axial offset control (CAOC) strategy during load maneuvers. An expert system using CAOC strategy, fuzzy reasoning, a two-node core model, and operational constraints has been developed. The computation time is so short that this system, which leads to an approximate closed-loop control, could be useful for on-site calculation

  9. Maintenance Maneuver Automation for an Adapted Cylindrical Shape TEC

    Rafael Morales

    2016-09-01

    Full Text Available Several manufacturers have developed devices with which to harness tidal/current power in areas where the depth does not exceed 40 m. These are the so-called first generation Tidal Energy Converters (TEC, and they are usually fixed to the seabed by gravity. When carrying out maintenance tasks on these devices it is, therefore, necessary to remove the nacelles from their bases and raise them to the surface of the sea. They must subsequently be placed back on their bases. These tasks require special high performance ships, signifying high maintenance costs. The automation of emersion and immersion maneuvers will undoubtedly lead to lower costs, given that ships with less demanding requirements will be required for the aforementioned maintenance tasks. This research presents a simple two degrees of freedom dynamic model that can be used to control a first generation TEC that has been conceived of to harness energy from marine currents. The control of the system is carried out by means of a water ballast system located inside the nacelle of the main power unit and is used as an actuator to produce buoying vertical forces. A nonlinear control law based on a decoupling term for the closed loop depth and/or orientation control is also proposed in order to ensure adequate behavior when the TEC performs emersion and immersion maneuvers with only hydrostatic buoyancy forces. The control scheme is composed of an inner loop consisting of a linear and decoupled input/output relationship and the vector of friction and compressibility terms and an outer loop that operates with the tracking error vector in order to ensure the asymptotically exponential stability of the TEC posture. Finally, the effectiveness of the dynamic model and the controller approach is demonstrated by means of numerical simulations when the TEC is carrying out an emersion maneuver for the development of general maintenance tasks and an emersion maneuver for blade-cleaning maintenance

  10. Silver nanoclusters-assisted ion-exchange reaction with CdTe quantum dots for photoelectrochemical detection of adenosine by target-triggering multiple-cycle amplification strategy.

    Zhao, Yang; Tan, Lu; Gao, Xiaoshan; Jie, Guifen; Huang, Tingyu

    2018-07-01

    Herein, we successfully devised a novel photoelectrochemical (PEC) platform for ultrasensitive detection of adenosine by target-triggering cascade multiple cycle amplification based on the silver nanoparticles-assisted ion-exchange reaction with CdTe quantum dots (QDs). In the presence of target adenosine, DNA s1 is released from the aptamer and then hybridizes with hairpin DNA (HP1), which could initiate the cycling cleavage process under the reaction of nicking endonuclease. Then the product (DNA b) of cycle I could act as the "DNA trigger" of cycle II to further generate a large number of DNA s1, which again go back to cycle I, thus a cascade multiple DNA cycle amplification was carried out to produce abundant DNA c. These DNA c fragments with the cytosine (C)-rich loop were captured by magnetic beads, and numerous silver nanoclusters (Ag NCs) were synthesized by AgNO 3 and sodium borohydride. The dissolved AgNCs released numerous silver ions which could induce ion exchange reaction with the CdTe QDs, thus resulting in greatly amplified change of photocurrent for target detection. The detection linear range for adenosine was 1.0 fM ~10 nM with the detection limit of 0.5 fM. The present PEC strategy combining cascade multiple DNA cycle amplification and AgNCs-induced ion-exchange reaction with QDs provides new insight into rapid, and ultrasensitive PEC detection of different biomolecules, which showed great potential for detecting trace amounts in bioanalysis and clinical biomedicine. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. ApicoAP: the first computational model for identifying apicoplast-targeted proteins in multiple species of Apicomplexa.

    Gokcen Cilingir

    Full Text Available Most of the parasites of the phylum Apicomplexa contain a relict prokaryotic-derived plastid called the apicoplast. This organelle is important not only for the survival of the parasite, but its unique properties make it an ideal drug target. The majority of apicoplast-associated proteins are nuclear encoded and targeted post-translationally to the organellar lumen via a bipartite signaling mechanism that requires an N-terminal signal and transit peptide (TP. Attempts to define a consensus motif that universally identifies apicoplast TPs have failed.In this study, we propose a generalized rule-based classification model to identify apicoplast-targeted proteins (ApicoTPs that use a bipartite signaling mechanism. Given a training set specific to an organism, this model, called ApicoAP, incorporates a procedure based on a genetic algorithm to tailor a discriminating rule that exploits the known characteristics of ApicoTPs. Performance of ApicoAP is evaluated for four labeled datasets of Plasmodium falciparum, Plasmodium yoelii, Babesia bovis, and Toxoplasma gondii proteins. ApicoAP improves the classification accuracy of the published dataset for P. falciparum to 94%, originally 90% using PlasmoAP.We present a parametric model for ApicoTPs and a procedure to optimize the model parameters for a given training set. A major asset of this model is that it is customizable to different parasite genomes. The ApicoAP prediction software is available at http://code.google.com/p/apicoap/ and http://bcb.eecs.wsu.edu.

  12. State Estimation for Landing Maneuver on High Performance Aircraft

    Suresh, P. S.; Sura, Niranjan K.; Shankar, K.

    2018-01-01

    State estimation methods are popular means for validating aerodynamic database on aircraft flight maneuver performance characteristics. In this work, the state estimation method during landing maneuver is explored for the first of its kind, using upper diagonal adaptive extended Kalman filter (UD-AEKF) with fuzzy based adaptive tunning of process noise matrix. The mathematical model for symmetrical landing maneuver consists of non-linear flight mechanics equation representing Aircraft longitudinal dynamics. The UD-AEKF algorithm is implemented in MATLAB environment and the states with bias is considered to be the initial conditions just prior to the flare. The measurement data is obtained from a non-linear 6 DOF pilot in loop simulation using FORTRAN. These simulated measurement data is additively mixed with process and measurement noises, which are used as an input for UD-AEKF. Then, the governing states that dictate the landing loads at the instant of touch down are compared. The method is verified using flight data wherein, the vertical acceleration at the aircraft center of gravity (CG) is compared. Two possible outcome of purely relying on the aircraft measured data is highlighted. It is observed that, with the implementation of adaptive fuzzy logic based extended Kalman filter tuned to adapt for aircraft landing dynamics, the methodology improves the data quality of the states that are sourced from noisy measurements.

  13. Development of power change maneuvering method for BWR

    Fukuzaki, Takaharu; Yamada, Naoyuki; Kiguchi, Takashi; Sakurai, Mikio.

    1985-01-01

    A power change maneuvering method for BWR has been proposed to generate an optimal power control maneuver, which realizes the power change operation closest to a power change demand pattern under operating constraints. The method searches for the maneuver as an optimization problem, where the variables are thermal power levels sampled from the demand pattern, the performance index is defined to express the power mismatch between demand and feasible patterns, and the constraints are limit lines on the thermal power-core flow rate map and limits on keeping fuel integrity. The usable feasible direction method is utilized as the optimization algorithm, with newly developed techniques for initial value generation and step length determination, which apply one-dimensional search and inverse-interpolation methods, respectively, to realize the effective search of the optimal solution. Simulation results show that a typical computing time is about 5 min by a general purpose computer and the method has been verified to be practical even for on-line use. (author)

  14. Capturing and analyzing wheelchair maneuvering patterns with mobile cloud computing.

    Fu, Jicheng; Hao, Wei; White, Travis; Yan, Yuqing; Jones, Maria; Jan, Yih-Kuen

    2013-01-01

    Power wheelchairs have been widely used to provide independent mobility to people with disabilities. Despite great advancements in power wheelchair technology, research shows that wheelchair related accidents occur frequently. To ensure safe maneuverability, capturing wheelchair maneuvering patterns is fundamental to enable other research, such as safe robotic assistance for wheelchair users. In this study, we propose to record, store, and analyze wheelchair maneuvering data by means of mobile cloud computing. Specifically, the accelerometer and gyroscope sensors in smart phones are used to record wheelchair maneuvering data in real-time. Then, the recorded data are periodically transmitted to the cloud for storage and analysis. The analyzed results are then made available to various types of users, such as mobile phone users, traditional desktop users, etc. The combination of mobile computing and cloud computing leverages the advantages of both techniques and extends the smart phone's capabilities of computing and data storage via the Internet. We performed a case study to implement the mobile cloud computing framework using Android smart phones and Google App Engine, a popular cloud computing platform. Experimental results demonstrated the feasibility of the proposed mobile cloud computing framework.

  15. A Fuel-Efficient Conflict Resolution Maneuver for Separation Assurance

    Bowe, Aisha Ruth; Santiago, Confesor

    2012-01-01

    Automated separation assurance algorithms are envisioned to play an integral role in accommodating the forecasted increase in demand of the National Airspace System. Developing a robust, reliable, air traffic management system involves safely increasing efficiency and throughput while considering the potential impact on users. This experiment seeks to evaluate the benefit of augmenting a conflict detection and resolution algorithm to consider a fuel efficient, Zero-Delay Direct-To maneuver, when resolving a given conflict based on either minimum fuel burn or minimum delay. A total of twelve conditions were tested in a fast-time simulation conducted in three airspace regions with mixed aircraft types and light weather. Results show that inclusion of this maneuver has no appreciable effect on the ability of the algorithm to safely detect and resolve conflicts. The results further suggest that enabling the Zero-Delay Direct-To maneuver significantly increases the cumulative fuel burn savings when choosing resolution based on minimum fuel burn while marginally increasing the average delay per resolution.

  16. Evaluation of Mathematical Models for Tankers’ Maneuvering Motions

    Erhan AKSU

    2017-03-01

    Full Text Available In this study, the maneuvering performance of two tanker ships, KVLCC1 and KVLCC2 which have different stern forms are predicted using a system-based method. Two different 3 DOF (degrees of freedom mathematical models based on the MMG(Maneuvering Modeling Group concept areappliedwith the difference in representing lateral force and yawing moment by second and third order polynomials respectively. Hydrodynamic coefficients and related parameters used in the mathematical models of the same scale models of KVLCC1 and KVLCC2 ships are estimated by using experimental data of NMRI (National Maritime Research Institute. The simulations of turning circle with rudder angle ±35o , zigzag(±10o /±10o and zigzag (±20o /±20o maneuvers are carried out and compared with free running model test data of MARIN (Maritime Research Institute Netherlands in this study. As a result of the analysis, it can be summarised that MMG model based on the third order polynomial is superior to the one based on the second order polynomial in view of estimation accuracy of lateral hull force and yawing moment.

  17. "Spaghetti Maneuver": A useful tool in pediatric laparoscopy - Our experience

    Antonio Marte

    2011-01-01

    Full Text Available Aims: The laparoscopic "Spaghetti Maneuver" consists in holding an organ by its extremity with a grasper and rolling it up around the tool to keep the organ stable and facilitate its traction within a small space. We describe our experience with the "Spaghetti Maneuver" in some minimally invasive procedures. Materials and Methods: We successfully adopted this technique in 13 patients (5F : 8M aged between 6 and 14 years (average age, 10 on whom we performed 7 appendectomies, 2 ureteral reimplantation and 4 cholecystectomies. In all cases, after the first steps, the appendix, the gallbladder and the ureter were rolled around the grasper and easily isolated; hemostasis was thus induced and the organ was mobilized until removal during cholecystectomy and appendectomy, and before the reimplantation in case of ureteral reimplantation. Results: We found that this technique facilitated significantly the acts of holding, isolating and removing, when necessary, the structures involved, which remained constantly within the visual field of the operator. This allowed a very ergonomic work setting, overcoming the problem of the "blind" zone, which represents a dangerous and invisible area out of the operator′s control during laparoscopy. Moreover the isolation maneuvers resulted easier and reduced operating time. Conclusion: We think that this technique is easy to perform and very useful, because it facilitates the dissection of these organs, by harmonizing and stabilizing the force of traction exercised.

  18. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan; Tan, Ren-Xiang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  19. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong; Gu, Yan-Hong; Shen, Yan; Tan, Ren-Xiang; Sun, Yang; Xu, Qiang

    2012-01-01

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  20. Automatic detection of multiple UXO-like targets using magnetic anomaly inversion and self-adaptive fuzzy c-means clustering

    Yin, Gang; Zhang, Yingtang; Fan, Hongbo; Ren, Guoquan; Li, Zhining

    2017-12-01

    We have developed a method for automatically detecting UXO-like targets based on magnetic anomaly inversion and self-adaptive fuzzy c-means clustering. Magnetic anomaly inversion methods are used to estimate the initial locations of multiple UXO-like sources. Although these initial locations have some errors with respect to the real positions, they form dense clouds around the actual positions of the magnetic sources. Then we use the self-adaptive fuzzy c-means clustering algorithm to cluster these initial locations. The estimated number of cluster centroids represents the number of targets and the cluster centroids are regarded as the locations of magnetic targets. Effectiveness of the method has been demonstrated using synthetic datasets. Computational results show that the proposed method can be applied to the case of several UXO-like targets that are randomly scattered within in a confined, shallow subsurface, volume. A field test was carried out to test the validity of the proposed method and the experimental results show that the prearranged magnets can be detected unambiguously and located precisely.

  1. Specific emotions as mediators of the effect of intergroup contact on prejudice: findings across multiple participant and target groups.

    Seger, Charles R; Banerji, Ishani; Park, Sang Hee; Smith, Eliot R; Mackie, Diane M

    2017-08-01

    Emotions are increasingly being recognised as important aspects of prejudice and intergroup behaviour. Specifically, emotional mediators play a key role in the process by which intergroup contact reduces prejudice towards outgroups. However, which particular emotions are most important for prejudice reduction, as well as the consistency and generality of emotion-prejudice relations across different in-group-out-group relations, remain uncertain. To address these issues, in Study 1 we examined six distinct positive and negative emotions as mediators of the contact-prejudice relations using representative samples of U.S. White, Black, and Asian American respondents (N = 639). Admiration and anger (but not other emotions) were significant mediators of the effects of previous contact on prejudice, consistently across different perceiver and target ethnic groups. Study 2 examined the same relations with student participants and gay men as the out-group. Admiration and disgust mediated the effect of past contact on attitude. The findings confirm that not only negative emotions (anger or disgust, based on the specific types of threat perceived to be posed by an out-group), but also positive, status- and esteem-related emotions (admiration) mediate effects of contact on prejudice, robustly across several different respondent and target groups.

  2. Anatomy and muscle activity of the dorsal fins in bamboo sharks and spiny dogfish during turning maneuvers.

    Maia, Anabela; Wilga, Cheryl D

    2013-11-01

    Stability and procured instability characterize two opposing types of swimming, steady and maneuvering, respectively. Fins can be used to manipulate flow to adjust stability during swimming maneuvers either actively using muscle control or passively by structural control. The function of the dorsal fins during turning maneuvering in two shark species with different swimming modes is investigated here using musculoskeletal anatomy and muscle function. White-spotted bamboo sharks are a benthic species that inhabits complex reef habitats and thus have high requirements for maneuverability. Spiny dogfish occupy a variety of coastal and continental shelf habitats and spend relatively more time cruising in open water. These species differ in dorsal fin morphology and fin position along the body. Bamboo sharks have a larger second dorsal fin area and proportionally more muscle insertion into both dorsal fins. The basal and radial pterygiophores are plate-like structures in spiny dogfish and are nearly indistinguishable from one another. In contrast, bamboo sharks lack basal pterygiophores, while the radial pterygiophores form two rows of elongated rectangular elements that articulate with one another. The dorsal fin muscles are composed of a large muscle mass that extends over the ceratotrichia overlying the radials in spiny dogfish. However, in bamboo sharks, the muscle mass is divided into multiple distinct muscles that insert onto the ceratotrichia. During turning maneuvers, the dorsal fin muscles are active in both species with no differences in onset between fin sides. Spiny dogfish have longer burst durations on the outer fin side, which is consistent with opposing resistance to the medium. In bamboo sharks, bilateral activation of the dorsal in muscles could also be stiffening the fin throughout the turn. Thus, dogfish sharks passively stiffen the dorsal fin structurally and functionally, while bamboo sharks have more flexible dorsal fins, which result from a

  3. Pyrosequencing the transcriptome of the greenhouse whitefly, Trialeurodes vaporariorum reveals multiple transcripts encoding insecticide targets and detoxifying enzymes

    Gorman Kevin

    2011-01-01

    Full Text Available Abstract Background The whitefly Trialeurodes vaporariorum is an economically important crop pest in temperate regions that has developed resistance to most classes of insecticides. However, the molecular mechanisms underlying resistance have not been characterised and, to date, progress has been hampered by a lack of nucleotide sequence data for this species. Here, we use pyrosequencing on the Roche 454-FLX platform to produce a substantial and annotated EST dataset. This 'unigene set' will form a critical reference point for quantitation of over-expressed messages via digital transcriptomics. Results Pyrosequencing produced around a million sequencing reads that assembled into 54,748 contigs, with an average length of 965 bp, representing a dramatic expansion of existing cDNA sequences available for T. vaporariorum (only 43 entries in GenBank at the time of this publication. BLAST searching of non-redundant databases returned 20,333 significant matches and those gene families potentially encoding gene products involved in insecticide resistance were manually curated and annotated. These include, enzymes potentially involved in the detoxification of xenobiotics and those encoding the targets of the major chemical classes of insecticides. A total of 57 P450s, 17 GSTs and 27 CCEs were identified along with 30 contigs encoding the target proteins of six different insecticide classes. Conclusion Here, we have developed new transcriptomic resources for T. vaporariorum. These include a substantial and annotated EST dataset that will serve the community studying this important crop pest and will elucidate further the molecular mechanisms underlying insecticide resistance.

  4. Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

    Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

    2017-01-01

    Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

  5. Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.

    Tamplin, Owen J; Cox, Brian J; Rossant, Janet

    2011-12-15

    The node and notochord are key tissues required for patterning of the vertebrate body plan. Understanding the gene regulatory network that drives their formation and function is therefore important. Foxa2 is a key transcription factor at the top of this genetic hierarchy and finding its targets will help us to better understand node and notochord development. We performed an extensive microarray-based gene expression screen using sorted embryonic notochord cells to identify early notochord-enriched genes. We validated their specificity to the node and notochord by whole mount in situ hybridization. This provides the largest available resource of notochord-expressed genes, and therefore candidate Foxa2 target genes in the notochord. Using existing Foxa2 ChIP-seq data from adult liver, we were able to identify a set of genes expressed in the notochord that had associated regions of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription factor, we reasoned that these sites might represent notochord-specific enhancers. Candidate Foxa2-bound regions were tested for notochord specific enhancer function in a zebrafish reporter assay and 7 novel notochord enhancers were identified. Importantly, sequence conservation or predictive models could not have readily identified these regions. Mutation of putative Foxa2 binding elements in two of these novel enhancers abrogated reporter expression and confirmed their Foxa2 dependence. The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Impact Angle and Time Control Guidance Under Field-of-View Constraints and Maneuver Limits

    Shim, Sang-Wook; Hong, Seong-Min; Moon, Gun-Hee; Tahk, Min-Jea

    2018-04-01

    This paper proposes a guidance law which considers the constraints of seeker field-of-view (FOV) as well as the requirements on impact angle and time. The proposed guidance law is designed for a constant speed missile against a stationary target. The guidance law consists of two terms of acceleration commands. The first one is to achieve zero-miss distance and the desired impact angle, while the second is to meet the desired impact time. To consider the limits of FOV and lateral maneuver capability, a varying-gain approach is applied on the second term. Reduction of realizable impact times due to these limits is then analyzed by finding the longest course among the feasible ones. The performance of the proposed guidance law is demonstrated by numerical simulation for various engagement conditions.

  7. Systematic approach to optimize a pretreatment method for ultrasensitive liquid chromatography with tandem mass spectrometry analysis of multiple target compounds in biological samples.

    Togashi, Kazutaka; Mutaguchi, Kuninori; Komuro, Setsuko; Kataoka, Makoto; Yamazaki, Hiroshi; Yamashita, Shinji

    2016-08-01

    In current approaches for new drug development, highly sensitive and robust analytical methods for the determination of test compounds in biological samples are essential. These analytical methods should be optimized for every target compound. However, for biological samples that contain multiple compounds as new drug candidates obtained by cassette dosing tests, it would be preferable to develop a single method that allows the determination of all compounds at once. This study aims to establish a systematic approach that enables a selection of the most appropriate pretreatment method for multiple target compounds without the use of their chemical information. We investigated the retention times of 27 known compounds under different mobile phase conditions and determined the required pretreatment of human plasma samples using several solid-phase and liquid-liquid extractions. From the relationship between retention time and recovery in a principal component analysis, appropriate pretreatments were categorized into several types. Based on the category, we have optimized a pretreatment method for the identification of three calcium channel blockers in human plasma. Plasma concentrations of these drugs in a cassette-dose clinical study at microdose level were successfully determined with a lower limit of quantitation of 0.2 pg/mL for diltiazem, 1 pg/mL for nicardipine, and 2 pg/mL for nifedipine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Treatment simulations with a statistical deformable motion model to evaluate margins for multiple targets in radiotherapy for high-risk prostate cancer

    Thörnqvist, Sara; Hysing, Liv B.; Zolnay, Andras G.; Söhn, Matthias; Hoogeman, Mischa S.; Muren, Ludvig P.; Bentzen, Lise; Heijmen, Ben J.M.

    2013-01-01

    Background and purpose: Deformation and correlated target motion remain challenges for margin recipes in radiotherapy (RT). This study presents a statistical deformable motion model for multiple targets and applies it to margin evaluations for locally advanced prostate cancer i.e. RT of the prostate (CTV-p), seminal vesicles (CTV-sv) and pelvic lymph nodes (CTV-ln). Material and methods: The 19 patients included in this study, all had 7–10 repeat CT-scans available that were rigidly aligned with the planning CT-scan using intra-prostatic implanted markers, followed by deformable registrations. The displacement vectors from the deformable registrations were used to create patient-specific statistical motion models. The models were applied in treatment simulations to determine probabilities for adequate target coverage, e.g. by establishing distributions of the accumulated dose to 99% of the target volumes (D 99 ) for various CTV–PTV expansions in the planning-CTs. Results: The method allowed for estimation of the expected accumulated dose and its variance of different DVH parameters for each patient. Simulations of inter-fractional motion resulted in 7, 10, and 18 patients with an average D 99 >95% of the prescribed dose for CTV-p expansions of 3 mm, 4 mm and 5 mm, respectively. For CTV-sv and CTV-ln, expansions of 3 mm, 5 mm and 7 mm resulted in 1, 11 and 15 vs. 8, 18 and 18 patients respectively with an average D 99 >95% of the prescription. Conclusions: Treatment simulations of target motion revealed large individual differences in accumulated dose mainly for CTV-sv, demanding the largest margins whereas those required for CTV-p and CTV-ln were comparable

  9. Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

    Wang, Lingshu; Shi, Wei; Chappell, James D.; Joyce, M. Gordon; Zhang, Yi; Kanekiyo, Masaru; Becker, Michelle M.; van Doremalen, Neeltje; Fischer, Robert; Wang, Nianshuang; Corbett, Kizzmekia S.; Choe, Misook; Mason, Rosemarie D.; Van Galen, Joseph G.; Zhou, Tongqing; Saunders, Kevin O.; Tatti, Kathleen M.; Haynes, Lia M.; Kwong, Peter D.; Modjarrad, Kayvon; Kong, Wing-Pui; McLellan, Jason S.; Denison, Mark R.; Munster, Vincent J.; Mascola, John R.; Graham, Barney S.; Gallagher, Tom

    2018-03-07

    ABSTRACT

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections.

    IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using

  10. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo.

    Qin Wang

    Full Text Available VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc.

  11. A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

    Ishida, M; Cullup, T; Boustred, C; James, C; Docker, J; English, C; Lench, N; Copp, A J; Moore, G E; Greene, N D E; Stanier, P

    2018-04-01

    Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Oridonin Targets Multiple Drug-Resistant Tumor Cells as Determined by in Silico and in Vitro Analyses

    Onat Kadioglu

    2018-04-01

    Full Text Available Drug resistance is one of the main reasons of chemotherapy failure. Therefore, overcoming drug resistance is an invaluable approach to identify novel anticancer drugs that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients for effective chemotherapy. Oridonin is a cytotoxic diterpenoid isolated from Rabdosia rubescens with in vivo anticancer activity. In the present study, we evaluated the cytotoxicity of oridonin toward a panel of drug-resistant cancer cells overexpressing ABCB1, ABCG2, or ΔEGFR or with a knockout deletion of TP53. Interestingly, oridonin revealed lower degree of resistance than the control drug, doxorubicin. Molecular docking analyses pointed out that oridonin can interact with Akt/EGFR pathway proteins with comparable binding energies and similar docking poses as the known inhibitors. Molecular dynamics results validated the stable conformation of oridonin docking pose on Akt kinase domain. Western blot experiments clearly revealed dose-dependent downregulation of Akt and STAT3. Pharmacogenomics analyses pointed to a mRNA signature that predicted sensitivity and resistance to oridonin. In conclusion, oridonin bypasses major drug resistance mechanisms and targets Akt pathway and might be effective toward drug refractory tumors. The identification of oridonin-specific gene expressions may be useful for the development of personalized treatment approaches.

  13. Comparative analysis of CD138 antigen targeting for the treatment of multiple myeloma with bismuth-213 and Melphalan chemotherapy

    Gouard, S.; Gaschet, J.; Maurel, C.; Barbet, J.; Davodeau, F.; Pallardy, A.; Faivre-Chauvet, A.; Kraeber-Bodere, F.; Bruchertseifer, F.; Morgenstern, A.; Cherel, M.

    2015-01-01

    Full text of publication follows. Aim: multiple myeloma (MM) is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow, with the presence of a monoclonal immunoglobulin in serum and/or urine and development of osteolytic bone lesions in human. Despite intense research to develop new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) has been shown to be effective in vivo in a multiple myeloma model and seems particularly suited for disseminated tumour cells or small clusters of tumour cells. CD138 (Syndecan-1) is found mainly in epithelial cells, but has been shown to be expressed by most myeloma cells, both in human and in mouse. In order to define where alpha RIT stands in MM treatment, the aim of this study was to compare Melphalan, MM standard treatment, with alpha RIT using a bismuth-213-labelled anti-mouse CD138 rat antibody in a syngeneic mouse MM model. Material and Methods: C57BL/KaLwRij mice were grafted with 10 6 5T33 cells (murine myeloma cells). Luciferase transfected 5T33 were used for in vivo localization of the cells during the course of disease. The first step of the study was to assess the dose-response of Melphalan (100, 200 et 300 μg/mouse), 21 days after engraftment. The second step consisted in therapeutic association: Melphalan followed by RIT at d22 et d25 after engraftment. Toxicity (animal weight, blood cell counts) and treatment efficacy were studied in animals receiving no treatment, injected with Melphalan alone (200 μg), RIT alone at d22 and d25 (3.7 MBq of 213 Bi-anti-CD138) and Melphalan combined with alpha RIT. Results: fifty percent of untreated mice died by d64 after MM engraftment. In mice treated with Melphalan alone, only the 200 μg dose improved median survival. No animal was cured after Melphalan treatment whereas 60% of the mice survived with RIT alone at d22 after tumour engraftment. However, the therapeutic window seems to be narrow, indeed no effect was observed with

  14. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    McGurk, Ross J. [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Bowsher, James; Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Lee, John A [Molecular Imaging and Experimental Radiotherapy Unit, Universite Catholique de Louvain, 1200 Brussels (Belgium)

    2013-04-15

    different between 128 Multiplication-Sign 128 and 256 Multiplication-Sign 256 grid sizes for either method (MJV, p= 0.0519; STAPLE, p= 0.5672) but was for SMASD values (MJV, p < 0.0001; STAPLE, p= 0.0164). The best individual method varied depending on object characteristics. However, both MJV and STAPLE provided essentially equivalent accuracy to using the best independent method in every situation, with mean differences in DSC of 0.01-0.03, and 0.05-0.12 mm for SMASD. Conclusions: Combining segmentations offers a robust approach to object segmentation in PET. Both MJV and STAPLE improved accuracy and were robust against the widely varying performance of individual segmentation methods. Differences between MJV and STAPLE are such that either offers good performance when combining volumes. Neither method requires a training dataset but MJV is simpler to interpret, easy to implement and fast.

  15. Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

    Weinger, Jason G; Plaisted, Warren C; Maciejewski, Sonia M; Lanier, Lewis L; Walsh, Craig M; Lane, Thomas E

    2014-10-01

    Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway. © 2014 AlphaMed Press.

  16. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  17. Using the Two-Burn Escape Maneuver for Fast Transfers in the Solar System and Beyond

    Adams, Robert B.; Richardson, Georgia A.

    2010-01-01

    The two-burn maneuver to escape the gravitational pull of a central body is described. The maneuver, originally suggested by Hermann Oberth, improves efficiency considerably for a wide range of missions of interest in space exploration and scientific investigation. A clear delineation of when the maneuver is more effective is given, as are methods to extract the most advantage when using the maneuver. Some examples are given of how this maneuver can enable exploration of the outer solar system, near interstellar space, and crewed missions to Mars and beyond. The maneuver has the potential to halve the required infrastructure associated with a crewed mission to Mars and achieve increased solar escape velocities with existing spacecraft technologies.

  18. Computing and Visualizing Reachable Volumes for Maneuvering Satellites

    Jiang, M.; de Vries, W.H.; Pertica, A.J.; Olivier, S.S.

    2011-01-01

    Detecting and predicting maneuvering satellites is an important problem for Space Situational Awareness. The spatial envelope of all possible locations within reach of such a maneuvering satellite is known as the Reachable Volume (RV). As soon as custody of a satellite is lost, calculating the RV and its subsequent time evolution is a critical component in the rapid recovery of the satellite. In this paper, we present a Monte Carlo approach to computing the RV for a given object. Essentially, our approach samples all possible trajectories by randomizing thrust-vectors, thrust magnitudes and time of burn. At any given instance, the distribution of the 'point-cloud' of the virtual particles defines the RV. For short orbital time-scales, the temporal evolution of the point-cloud can result in complex, multi-reentrant manifolds. Visualization plays an important role in gaining insight and understanding into this complex and evolving manifold. In the second part of this paper, we focus on how to effectively visualize the large number of virtual trajectories and the computed RV. We present a real-time out-of-core rendering technique for visualizing the large number of virtual trajectories. We also examine different techniques for visualizing the computed volume of probability density distribution, including volume slicing, convex hull and isosurfacing. We compare and contrast these techniques in terms of computational cost and visualization effectiveness, and describe the main implementation issues encountered during our development process. Finally, we will present some of the results from our end-to-end system for computing and visualizing RVs using examples of maneuvering satellites.

  19. Simulation of upwind maneuvering of a sailing yacht

    Harris, Daniel Hartrick

    A time domain maneuvering simulation of an IACC class yacht suitable for the analysis of unsteady upwind sailing including tacking is presented. The simulation considers motions in six degrees of freedom. The hydrodynamic and aerodynamic loads are calculated primarily with unsteady potential theory supplemented by empirical viscous models. The hydrodynamic model includes the effects of incident waves. Control of the rudder is provided by a simple rate feedback autopilot which is augmented with open loop additions to mimic human steering. The hydrodynamic models are based on the superposition of force components. These components fall into two groups, those which the yacht will experience in calm water, and those due to incident waves. The calm water loads are further divided into zero Froude number, or "double body" maneuvering loads, hydrostatic loads, gravitational loads, free surface radiation loads, and viscous/residual loads. The maneuvering loads are calculated with an unsteady panel code which treats the instantaneous geometry of the yacht below the undisturbed free surface. The free surface radiation loads are calculated via convolution of impulse response functions derived from seakeeping strip theory. The viscous/residual loads are based upon empirical estimates. The aerodynamic model consists primarily of a database of steady state sail coefficients. These coefficients treat the individual contributions to the total sail force of a number of chordwise strips on both the main and jib. Dynamic effects are modeled by using the instantaneous incident wind velocity and direction as the independent variables for the sail load contribution of each strip. The sail coefficient database was calculated numerically with potential methods and simple empirical viscous corrections. Additional aerodynamic load calculations are made to determine the parasitic contributions of the rig and hull. Validation studies compare the steady sailing hydro and aerodynamic loads

  20. Computing and Visualizing Reachable Volumes for Maneuvering Satellites

    Jiang, M.; de Vries, W.; Pertica, A.; Olivier, S.

    2011-09-01

    Detecting and predicting maneuvering satellites is an important problem for Space Situational Awareness. The spatial envelope of all possible locations within reach of such a maneuvering satellite is known as the Reachable Volume (RV). As soon as custody of a satellite is lost, calculating the RV and its subsequent time evolution is a critical component in the rapid recovery of the satellite. In this paper, we present a Monte Carlo approach to computing the RV for a given object. Essentially, our approach samples all possible trajectories by randomizing thrust-vectors, thrust magnitudes and time of burn. At any given instance, the distribution of the "point-cloud" of the virtual particles defines the RV. For short orbital time-scales, the temporal evolution of the point-cloud can result in complex, multi-reentrant manifolds. Visualization plays an important role in gaining insight and understanding into this complex and evolving manifold. In the second part of this paper, we focus on how to effectively visualize the large number of virtual trajectories and the computed RV. We present a real-time out-of-core rendering technique for visualizing the large number of virtual trajectories. We also examine different techniques for visualizing the computed volume of probability density distribution, including volume slicing, convex hull and isosurfacing. We compare and contrast these techniques in terms of computational cost and visualization effectiveness, and describe the main implementation issues encountered during our development process. Finally, we will present some of the results from our end-to-end system for computing and visualizing RVs using examples of maneuvering satellites.

  1. Maneuvering a pilot implementation to align agendas across sectors

    Mønsted, Troels; Hertzum, Morten; Søndergaard, Jens

    2017-01-01

    A prerequisite for pilot implementations in complex organizational settings is that the agendas of the stakeholders of the system are maneuvered into alignment. In this paper we present a study of the pilot implementation of the IT-supported, preventive intervention TOF (Tidlig Opsporing og...... Forebyggelse). A core element of TOF is an IT system that stratifies citizens into risk groups on the basis of self-reported lifestyle information and data retrieved from the medical records of the general practitioners (GPs). In addition, the system facilitates cross-sectoral coordination between preventive...

  2. Improving aggregate behavior in parking lots with appropriate local maneuvers

    Rodriguez, Samuel

    2013-11-01

    In this paper we study the ingress and egress of pedestrians and vehicles in a parking lot. We show how local maneuvers executed by agents permit them to create trajectories in constrained environments, and to resolve the deadlocks between them in mixed-flow scenarios. We utilize a roadmap-based approach which allows us to map complex environments and generate heuristic local paths that are feasible for both pedestrians and vehicles. Finally, we examine the effect that some agent-behavioral parameters have on parking lot ingress and egress. © 2013 IEEE.

  3. Space Shuttle OMS engine valve technology. [Orbital Maneuvering System

    Wichmann, H.

    1974-01-01

    Valve technology program to determine shutoff valve concepts suitable for the Orbital Maneuvering System (OMS) engine of the Space Shuttle. The tradeoff studies selected the electric torque motor operated dual poppet and ball valves as the most desirable valve concepts for the OMS Engine Shutoff Valve. A prototype of one of these concepts was built and subjected to a design verification program. A number of unique features were designed to include the required contamination insensitivity, operating fluid compatibility, decontamination capability, minimum maintenance requirement and long service life capability.

  4. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

    Mackenzie, Robertson; Kommoss, Stefan; Winterhoff, Boris J.; Kipp, Benjamin R.; Garcia, Joaquin J.; Voss, Jesse; Halling, Kevin; Karnezis, Anthony; Senz, Janine; Yang, Winnie; Prigge, Elena-Sophie; Reuschenbach, Miriam; Doeberitz, Magnus Von Knebel; Gilks, Blake C.; Huntsman, David G.; Bakkum-Gamez, Jamie; McAlpine, Jessica N.; Anglesio, Michael S.

    2015-01-01

    populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event. Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway “double-hits” supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations. The online version of this article (doi:10.1186/s12885-015-1421-8) contains supplementary material, which is available to authorized users

  5. MO-C-17A-06: Online Adaptive Re-Planning to Account for Independent Motions Between Multiple Targets During Radiotherapy of Lung Cancer

    Liu, F; Tai, A; Ahunbay, E; Gore, E; Johnstone, C; Li, X

    2014-01-01

    Purpose: To quantify interfractional independent motions between multiple targets in radiotherapy (RT) of lung cancer, and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. Methods: Ninety five diagnostic-quality daily CTs acquired for 9 lung cancer patients treated with IGRT using an in-room CT (CTVision, Siemens) were analyzed. On each daily CT set, contours of the targets (GTV, CTV, or involved nodes) and organs at risk were generated by populating the planning contours using an auto-segmentation tool (ABAS, Elekta) with manual editing. For each patient, an IMRT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2Gy fractions. Three plans were generated and compared for each daily CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes and segment weights of the original plan to conform to the daily anatomy, and a new fully re-optimized plan based on the daily CT using a planning system (Panther, Prowess). Results: The daily deviations of the distance between centers of masses of the targets from the plans varied daily from -10 to 8 mm with an average −0.9±4.1 mm (one standard deviation). The average CTV V100 are 99.0±0.7%, 97.9±2.8%, 99.0±0.6%, and 99.1±0.6%, and the lung V20 Gy 928±332 cc, 944±315 cc, 917±300 cc, and 891±295 cc for the original, repositioning, adaptive, and re-optimized plans, respectively. Wilcoxon signed-rank tests show that the adaptive plans are statistically significantly better than the repositioning plans and comparable with the reoptimized plans. Conclusion: There exist unpredictable, interfractional, relative volume changes and independent motions between multiple targets during lung cancer RT which cannot be accounted for by the current IGRT repositioning but can be corrected by the online adaptive replanning method

  6. MO-C-17A-06: Online Adaptive Re-Planning to Account for Independent Motions Between Multiple Targets During Radiotherapy of Lung Cancer

    Liu, F; Tai, A; Ahunbay, E; Gore, E; Johnstone, C; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2014-06-15

    Purpose: To quantify interfractional independent motions between multiple targets in radiotherapy (RT) of lung cancer, and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. Methods: Ninety five diagnostic-quality daily CTs acquired for 9 lung cancer patients treated with IGRT using an in-room CT (CTVision, Siemens) were analyzed. On each daily CT set, contours of the targets (GTV, CTV, or involved nodes) and organs at risk were generated by populating the planning contours using an auto-segmentation tool (ABAS, Elekta) with manual editing. For each patient, an IMRT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2Gy fractions. Three plans were generated and compared for each daily CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes and segment weights of the original plan to conform to the daily anatomy, and a new fully re-optimized plan based on the daily CT using a planning system (Panther, Prowess). Results: The daily deviations of the distance between centers of masses of the targets from the plans varied daily from -10 to 8 mm with an average −0.9±4.1 mm (one standard deviation). The average CTV V100 are 99.0±0.7%, 97.9±2.8%, 99.0±0.6%, and 99.1±0.6%, and the lung V20 Gy 928±332 cc, 944±315 cc, 917±300 cc, and 891±295 cc for the original, repositioning, adaptive, and re-optimized plans, respectively. Wilcoxon signed-rank tests show that the adaptive plans are statistically significantly better than the repositioning plans and comparable with the reoptimized plans. Conclusion: There exist unpredictable, interfractional, relative volume changes and independent motions between multiple targets during lung cancer RT which cannot be accounted for by the current IGRT repositioning but can be corrected by the online adaptive replanning method.

  7. Limited War in the Precision Engagement Era: The Balance Between Dominant Maneuver and Precision Engagement

    Hedstrom, Marvin

    2001-01-01

    .... German historian Hans Delbruck's two strategies of warfare: annihilation and exhaustion, and American military theorist Robert Leonhard's concepts of attrition and maneuver are examined to establish the relationship...

  8. Study on zigzag maneuver characteristics of V-U very large crude oil (VLCC) tankers

    Jaswar, Maimun, A.; Wahid, M. A.; Priyanto, A.; Zamani, Pauzi, Saman

    2012-06-01

    The Department of Marine Technology at the Faculty of Mechanical Engineering, University Teknologi Malaysia has recently developed an Ship Maneuverability tool which intends to upgrade student's level understanding the application of fluid dynamic on interaction between hull, propeller, and rudder during maneuvering. This paper discusses zigzag maneuver for conventional Very Large Crude Oil (VLCC) ships with the same principal dimensions but different stern flame shape. 10/10 zigzag maneuver characteristics of U and V types of VLCC ships are investigated. Simulation results for U-type show a good agreement with the experimental data, but V-type not good agreement with experimental one. Further study on zigzag maneuver characteristics are required.

  9. Performance of the multiple target He/PbI sub 2 aerosol jet system for mass separation of neutron-deficient actinide isotopes

    Ichikawa, S; Asai, M; Haba, H; Sakama, M; Kojima, Y; Shibata, M; Nagame, Y; Oura, Y; Kawade, K

    2002-01-01

    A multiple target He/PbI sub 2 aerosol jet system coupled with a thermal ion source was installed in the isotope separator on line (JAERI-ISOL) at the JAERI tandem accelerator facility. The neutron-deficient americium and curium isotopes produced in the sup 2 sup 3 sup 3 sup , sup 2 sup 3 sup 5 U( sup 6 Li, xn) and sup 2 sup 3 sup 7 Np( sup 6 Li, xn) reactions were successfully mass-separated and the overall efficiency including the ionization of Am atoms was evaluated to be 0.3-0.4%. The identification of a new isotope sup 2 sup 3 sup 7 Cm with the present system is reported.

  10. How hummingbirds hum: Acoustic holography of hummingbirds during maneuvering flight

    Hightower, Ben; Wijnings, Patrick; Ingersoll, Rivers; Chin, Diana; Scholte, Rick; Lentink, David

    2017-11-01

    Hummingbirds make a characteristic humming sound when they flap their wings. The physics and the biological significance of hummingbird aeroacoustics is still poorly understood. We used acoustic holography and high-speed cameras to determine the acoustic field of six hummingbirds while they either hovered stationary in front of a flower or maneuvered to track flower motion. We used a robotic flower that oscillated either laterally or longitudinally with a linear combination of 20 different frequencies between 0.2 and 20 Hz, a range that encompasses natural flower vibration frequencies in wind. We used high-speed marker tracking to dissect the transfer function between the moving flower, the head, and body of the bird. We also positioned four acoustic arrays equipped with 2176 microphones total above, below, and in front of the hummingbird. Acoustic data from the microphones were back-propagated to planes adjacent to the hummingbird to create the first real-time holograms of the pressure field a hummingbird generates in vivo. Integration of all this data offers insight into how hummingbirds modulate the acoustic field during hovering and maneuvering flight.

  11. A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma

    Tomofumi Yamamoto

    2018-03-01

    Full Text Available Multiple myeloma (MM is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs were shown to modulate the expression of genes critical for MM pathogenesis. In addition, miRNAs are secreted via extracellular vesicles (EVs, which are released from various cell types including MM cells, and these miRNAs are involved in multiple types of cell-cell interactions, which lead to the malignancy of MM. In this review, we summarize the current knowledge regarding the role of miRNA secretion via EVs and of EVs themselves in MM development. We also discuss the potential clinical applications of EVs as promising biomarkers and new therapeutic targets for improving the outcome of MM, resulting in a brighter future for aging societies.

  12. Single-photon sensitive fast ebCMOS camera system for multiple-target tracking of single fluorophores: application to nano-biophotonics

    Cajgfinger, Thomas; Chabanat, Eric; Dominjon, Agnes; Doan, Quang T.; Guerin, Cyrille; Houles, Julien; Barbier, Remi

    2011-03-01

    Nano-biophotonics applications will benefit from new fluorescent microscopy methods based essentially on super-resolution techniques (beyond the diffraction limit) on large biological structures (membranes) with fast frame rate (1000 Hz). This trend tends to push the photon detectors to the single-photon counting regime and the camera acquisition system to real time dynamic multiple-target tracing. The LUSIPHER prototype presented in this paper aims to give a different approach than those of Electron Multiplied CCD (EMCCD) technology and try to answer to the stringent demands of the new nano-biophotonics imaging techniques. The electron bombarded CMOS (ebCMOS) device has the potential to respond to this challenge, thanks to the linear gain of the accelerating high voltage of the photo-cathode, to the possible ultra fast frame rate of CMOS sensors and to the single-photon sensitivity. We produced a camera system based on a 640 kPixels ebCMOS with its acquisition system. The proof of concept for single-photon based tracking for multiple single-emitters is the main result of this paper.

  13. Parallel solid-phase isothermal amplification and detection of multiple DNA targets in microliter-sized wells of a digital versatile disc

    Santiago-Felipe, Sara; Tortajada-Genaro, Luis Antonio; Puchades, Rosa; Maquieira, Ángel

    2016-01-01

    An integrated method for the parallelized detection of multiple DNA target sequences is presented by using microstructures in a digital versatile disc (DVD). Samples and reagents were managed by using both the capillary and centrifugal forces induced by disc rotation. Recombinase polymerase amplification (RPA), in a bridge solid phase format, took place in separate wells, which thereby modified their optical properties. Then the DVD drive reader recorded the modifications of the transmitted laser beam. The strategy allowed tens of genetic determinations to be made simultaneously within <2 h, with small sample volumes (3 μL), low manipulation and at low cost. The method was applied to high-throughput screening of relevant safety threats (allergens, GMOs and pathogenic bacteria) in food samples. Satisfactory results were obtained in terms of sensitivity (48.7 fg of DNA) and reproducibility (below 18 %). This scheme warrants cost-effective multiplex amplification and detection and is perceived to represent a viable tool for screening of nucleic acid targets. (author)

  14. Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo.

    Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J; Palmer, Ira; Kaufman, Joshua D; Nadaud, Philippe S; Mukherjee, Sujoy; Wingfield, Paul T; Jaroniec, Christopher P; Hinnebusch, Alan G

    2010-01-22

    Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4Delta cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.

  15. Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90

    Xu Yuan-Ji

    2011-08-01

    Full Text Available Abstract Background Multiple myeloma (MM is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.

  16. miR-320a regulates cell proliferation and apoptosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor 3

    Lu, Yinghao [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Wu, Depei, E-mail: wudepei@medmail.com.cn [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Wang, Jishi, E-mail: lgylhlyh@aliyun.com [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Li, Yan; Chai, Xiao; Kang, Qian [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China)

    2016-05-13

    Aberrant expression of microRNAs (miRNAs) is implicated in cancer development and progression. While miR-320a is reported to be deregulated in many malignancy types, its biological role in multiple myeloma (MM) remains unclear. Here, we observed reduced expression of miR-320a in MM samples and cell lines. Ectopic expression of miR-320a dramatically suppressed cell viability and clonogenicity and induced apoptosis in vitro. Mechanistic investigation led to the identification of Pre-B-cellleukemia transcription factor 3 (PBX3) as a novel and direct downstream target of miR-320a. Interestingly, reintroduction of PBX3 abrogated miR-320a-induced MM cell growth inhibition and apoptosis. In a mouse xenograft model, miR-320a overexpression inhibited tumorigenicity and promoted apoptosis. Our findings collectively indicate that miR-320a inhibits cell proliferation and induces apoptosis in MM cells by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for miRNA-based MM therapy. -- Highlights: •Expression of miR-320a in MM cell induces apoptosis in vitro. •miR-320a represses PBX3 via targeting specific sequences in the 3′UTR region. •Exogenous expression of PBX3 reverses the effects of miR-320a in inhibiting MM cell growth and promoting apoptosis. •Overexpression of miR-320a inhibits tumor growth and increases apoptosis in vivo.

  17. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  18. Damage to tungsten macro-brush targets under multiple ELM-like heat loads. Experiments vs. numerical simulations and extrapolation to ITER

    Bazylev, B.; Landman, I. [Forschungszentrum Karlsruhe (Germany). IHM; Janeschitz, G. [Forschungszentrum Karlsruhe (DE). Fusion EURATOM] (and others)

    2007-07-01

    Operation of ITER at high fusion gain is assumed to be the H-mode. A characteristic feature of this regime is the transient release of energy from the confined plasma onto PFCs by multiple ELMs (about 104 ELMs per ITER discharge), which can play a determining role in the erosion rate and lifetime of these components. The expected energy heat loads on the ITER divertor during Type I ELM are in range 0.5-4 MJ/m{sup 2} in timescales of 0.3-0.6 ms. Tungsten macro-brush armour (W-brushes) is foreseen as one of plasma facing components (PFC) for ITER divertor and dome. During the intense transient events in ITER the surface melting, melt motion, melt splashing and evaporation are seen as the main mechanisms of W erosion. The expected erosion of the ITER plasma facing components under transient energy loads can be properly estimated by numerical simulations validated against target erosion of the experiments at the plasma gun facility QSPA-T. Within the collaboration established between EU fusion programme and the Russian Federation, W-brush targets (produced either from pure tungsten or tungsten with 1% of La{sub 2}O{sub 3}) manufactured according to the EU specifications for the ITER divertor targets, have been exposed to multiple ITER ELM-like loads in plasma gun facilities at TRINITI in the range 0.5 - 2.2 MJ/m2 with pulse duration of 0.5 ms. The measured material erosion data have been used to validate the codes MEMOS and PHEMOBRID. Numerical simulations, including 3D-simulations (codes MEMOS and PHEMOBRID), carried out for the conditions of the QSPA-T experiments with heat loads in the range 0.5-2.2 MJ/m{sup 2} and the timescale 0.5 ms demonstrated a rather good agreement with the data obtained at the plasma gun facility QSPA: melting of brush edges at low heat loads, intense melt motion and bridge formation caused by the Rayleigh-Taylor instability at heat loads Q>1.3 MJ/m{sup 2}. The melt splashing generated by the Kelvin-Helmholtz, and Rayleigh

  19. The effects of betahistine in addition to epley maneuver in posterior canal benign paroxysmal positional vertigo.

    Guneri, Enis Alpin; Kustutan, Ozge

    2012-01-01

    The purpose of this study is to evaluate the effects of betahistine in addition to Epley maneuver on the quality of life of patients with posterior semicircular canal benign paroxysmal positional vertigo (BPPV) of the canalithiasis type. Double-blind, randomized, controlled clinical trial. Academic university hospital. Seventy-two patients were enrolled in the study. The first group was treated with Epley maneuver only. The second group received placebo drug 2 times daily for 1 week in addition to Epley maneuver, and the third group received 24 mg betahistine 2 times daily for 1 week in addition to Epley maneuver. The effectiveness of the treatments was assessed in each group as well as between them by analyzing and comparing data of 4 different vertigo symptom scales. Epley maneuver, alone or combined with betahistine or placebo, was found to be very effective with a primary success rate of 86.2%. The symptoms were significantly reduced in group 3 patients overall, and those patients younger or older than 50 years of age who had hypertension, with symptom onset <1 month, and with attack duration of less than a minute did significantly better with the combination of betahistine 48 mg daily. Betahistine in addition to Epley maneuver is more effective than Epley maneuver alone or combined with placebo with regard to improvement of symptoms in certain patients. However, future clinical studies covering more patients to investigate the benefit of medical treatments in addition to Epley maneuver are needed.

  20. 32 CFR 552.38 - Acquisition of maneuver agreements for Army commanders.

    2010-07-01

    ... Real Estate and Interest Therein § 552.38 Acquisition of maneuver agreements for Army commanders. (a... specific areas desired for use. (b) Real estate coverage. Real estate coverage will be in the form of agreements with landowners, granting the right to conduct maneuvers at a given time or periodically. Short...

  1. Closeup of STS-26 Discovery, OV-103, orbital maneuvering system (OMS) leak

    1988-01-01

    Closeup of STS-26 Discovery, Orbiter Vehicle (OV) 103, orbital maneuvering system (OMS) reaction control system (RCS) nitrogen tetroxide gas leak was captured by a Cobra borescope and displayed on a video monitor. The borescope has a miniature videocamera at the end of a flexible rubber tube and is able to be maneuvered into other inaccessible locations.

  2. Applying Dynamical Systems Theory to Optimize Libration Point Orbit Stationkeeping Maneuvers for WIND

    Brown, Jonathan M.; Petersen, Jeremy D.

    2014-01-01

    NASA's WIND mission has been operating in a large amplitude Lissajous orbit in the vicinity of the interior libration point of the Sun-Earth/Moon system since 2004. Regular stationkeeping maneuvers are required to maintain the orbit due to the instability around the collinear libration points. Historically these stationkeeping maneuvers have been performed by applying an incremental change in velocity, or (delta)v along the spacecraft-Sun vector as projected into the ecliptic plane. Previous studies have shown that the magnitude of libration point stationkeeping maneuvers can be minimized by applying the (delta)v in the direction of the local stable manifold found using dynamical systems theory. This paper presents the analysis of this new maneuver strategy which shows that the magnitude of stationkeeping maneuvers can be decreased by 5 to 25 percent, depending on the location in the orbit where the maneuver is performed. The implementation of the optimized maneuver method into operations is discussed and results are presented for the first two optimized stationkeeping maneuvers executed by WIND.

  3. Concomitant targeting of multiple key transcription factors effectively disrupts cancer stem cells enriched in side population of human pancreatic cancer cells.

    Xiyan Wang

    Full Text Available A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs.To identify side population (SP cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.CSCs were enriched in the side proportion (SP cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a

  4. Platelet injectors for Space Shuttle orbit maneuvering engine

    Kahl, R. C.; Labotz, R. J.; Bassham, L. B.

    1974-01-01

    The Space Shuttle Orbit Maneuvering Subsystem Rocket Engine employs a platelet element injector concept. This injector has demonstrated 316-sec vacuum specific impulse performance under simulated altitude conditions when tested with a milled slot/electroformed nickel close-out regenerative chamber and a full 71 area ratio nozzle. To date, over 300 altitude engine tests and 300 stability bomb tests have demonstrated stable, erosion free operation with this concept to test durations of 150 seconds. The injector and chamber also meet the reusable requirements of the shuttle with a cycle life capability in excess of 1000 cycles. An extensive altitude restart program has also demonstrated OMS-engine operation over large variations in the burn and coast times with helium saturated propellants.

  5. Space shuttle orbital maneuvering engine platelet injector program

    1975-01-01

    A platelet-face injector for the fully reusable orbit maneuvering system OMS on the space shuttle was evaluated as a means of obtaining additional design margin and low cost. Performance, heat transfer, and combustion stability were evaluated over the anticipated range of OMS operating conditions. The effects of acoustic cavity configuration on combustion stability, including cavity depth, open area, inlet contour, and other parameters, were investigated using sea level bomb tests. Prototype injector and chamber behavior was evaluated for a variety of conditions; these tests examined the effects of film cooling, helium saturated propellants, chamber length, inlet conditions, and operating point, on performance, heat transfer and engine transient behavior. Helium bubble ingestion into both propellant circuits was investigated, as was chugging at low pressure operation, and hot and cold engine restart with and without a purge.

  6. Helicopter Acoustic Flight Test with Altitude Variation and Maneuvers

    Watts, Michael E.; Greenwood, Eric; Sim, Ben; Stephenson, James; Smith, Charles D.

    2016-01-01

    A cooperative flight test campaign between NASA and the U.S. Army was performed from September 2014 to February 2015. The purposes of the testing were to: investigate the effects of altitude variation on noise generation, investigate the effects of gross weight variation on noise generation, establish the statistical variability in acoustic flight testing of helicopters, and characterize the effects of transient maneuvers on radiated noise for a medium-lift utility helicopter. This test was performed at three test sites (0, 4000, and 7000 feet above mean sea level) with two aircraft (AS350 SD1 and EH-60L) tested at each site. This report provides an overview of the test, documents the data acquired and describes the formats of the stored data.

  7. Sequential Probability Ratio Test for Spacecraft Collision Avoidance Maneuver Decisions

    Carpenter, J. Russell; Markley, F. Landis

    2013-01-01

    A document discusses sequential probability ratio tests that explicitly allow decision-makers to incorporate false alarm and missed detection risks, and are potentially less sensitive to modeling errors than a procedure that relies solely on a probability of collision threshold. Recent work on constrained Kalman filtering has suggested an approach to formulating such a test for collision avoidance maneuver decisions: a filter bank with two norm-inequality-constrained epoch-state extended Kalman filters. One filter models the null hypotheses that the miss distance is inside the combined hard body radius at the predicted time of closest approach, and one filter models the alternative hypothesis. The epoch-state filter developed for this method explicitly accounts for any process noise present in the system. The method appears to work well using a realistic example based on an upcoming, highly elliptical orbit formation flying mission.

  8. Non-Toxic Orbital Maneuvering System Engine Development

    Green, Christopher; Claflin, Scott; Maeding, Chris; Butas, John

    1999-01-01

    Recent results using the Aestus engine operated with LOx/ethanol propellant are presented. An experimental program at Rocketdyne Propulsion and Power is underway to adapt this engine for the Boeing Reusable Space Systems Division non-toxic Orbital Maneuvering System/Reaction control System (OMS/RCS) system. Daimler-Chrysler Aerospace designed the Aestus as an nitrogen tetroxide/monomethyl hydrazine (NTO/MMH) upper-stage engine for the Ariane 5. The non-toxic OMS/RCS system's preliminary design requires a LOx/ethanol (O2/C2H5OH) engine that operates with a mixture ratio of 1.8, a specific impulse of 323 seconds, and fits within the original OMS design envelope. This paper describes current efforts to meet these requirements including, investigating engine performance using LOx/ethanol, developing the en-ine system sizing package, and meeting the vehicle operation parameters. Data from hot-fire testing are also presented and discussed.

  9. Nuclear space power systems for orbit raising and maneuvering

    Buden, D.; Sullivan, J.A.

    1984-01-01

    Reference is made to recent studies which have shown that direct thrust nuclear rockets for routine orbit raising and near-earth space tug missions are probably not cost-effective. The need for additional trade-off studies and comparisons of direct-thrust nuclear systems with chemical systems to clarify the role of nuclear rockets in missions requiring rapid orbit maneuvering is stressed. Attention is confined here to nuclear electric propulsion considerations. Low-mass nuclear power plants are constructed to optimize nuclear electric propulsion systems. Electric power levels from 100 kilowatts to as much as several megawatts are desirable. The goals for the power plant specific mass are 20-30 kg/kW at the lower powers to 2-4 kg/kW at the higher powers

  10. Identification and risk estimation of movement strategies during cutting maneuvers.

    David, Sina; Komnik, Igor; Peters, Markus; Funken, Johannes; Potthast, Wolfgang

    2017-12-01

    Approximately 70% of anterior cruciate ligament (ACL) injuries occur in non-contact situations during cutting and landing maneuvers. Parameters such as footstrike patterns and trunk orientation were found to influence ACL relevant knee loading, however, the relationship between the whole body movement and injury risk is debated. This study identifies whole body movement strategies that increase injury risk, and provides training recommendations to reduce this risk or enable a save return to sports after injury. Experimental cross-sectional study design. Three dimensional movement analysis was carried out to investigate 50 participants performing anticipated 90° cutting maneuvers. To identify and characterize movement strategies, footstrike pattern, knee valgus moment, knee internal rotation moment, angle of attack, shoulder and pelvis axis were analyzed using statistical parametric mapping. Three different movement strategies were identified. One strategy included rearfoot striking in combination with a relatively upright body position which generated higher knee joint loads than the second strategy, forefoot striking in combination with more backwards leaning and pre-rotation of the trunk towards the new movement direction. A third strategy combined forefoot striking with less preorientation which increased the ACL relevant knee joint load compared to the second strategy. The identified movement strategies clearly pre-determine the injury risk during non-contact situations with the third strategy as the most unfavorable one. Compared to the study of isolated parameters, the analysis of the whole body movement allowed for detailed separation of more risky from less risky cutting strategies. These results give practical recommendations for the prevention of ACL injury. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  11. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example

    Rosewall, Tara; Alasti, Hamideh; Bayley, Andrew; Yan, Jing

    2017-01-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2 = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were −0.4 to 1.8 mm (LR), −1.2 to 5.2 mm (SI) and −1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

  12. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

    Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

    2017-04-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

  13. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma

    Baumann, Philipp; Mandl-Weber, Sonja; Oduncu, Fuat; Schmidmaier, Ralf

    2009-01-01

    NVP-BEZ235 is a new inhibitor of phosphoinositol-3-kinase (PI3 kinase) and mammalian target of rapamycin (mTOR) whose efficacy in advanced solid tumours is currently being evaluated in a phase I/II clinical trial. Here we show that NVP-BEZ235 inhibits growth in common myeloma cell lines as well as primary myeloma cells at nanomolar concentrations in a time and dose dependent fashion. Further experiments revealed induction of apoptosis in three of four cell lines. Inhibition of cell growth was mainly due to inhibition of myeloma cell proliferation, as shown by the BrdU assay. Cell cycle analysis revealed induction of cell cycle arrest in the G1 phase, which was due to downregulation of cyclin D1, pRb and cdc25a. NVP-BEZ235 inhibited phosphorylation of protein kinase B (Akt), P70S6k and 4E-BP-1. Furthermore we show that the stimulatory effect of CD40-ligand (CD40L), insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6) and conditioned medium of HS-5 stromal cells on myeloma cell growth is completely abrogated by NVP-BEZ235. In addition, synergism studies revealed synergistic and additive activity of NVP-BEZ235 together with melphalan, doxorubicin and bortezomib. Taken together, inhibition of PI3 kinase/mTOR by NVP-BEZ235 is highly effective and NVP-BEZ235 represents a potential new candidate for targeted therapy in multiple myeloma

  14. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Qi Wang

    Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  15. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

    2013-01-01

    To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+) current. H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2), with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  16. Propulsion System and Orbit Maneuver Integration in CubeSats: Trajectory Control Strategies Using Micro Ion Propulsion

    Hudson, Jennifer; Martinez, Andres; Petro, Andrew

    2015-01-01

    The Propulsion System and Orbit Maneuver Integration in CubeSats project aims to solve the challenges of integrating a micro electric propulsion system on a CubeSat in order to perform orbital maneuvers and control attitude. This represents a fundamentally new capability for CubeSats, which typically do not contain propulsion systems and cannot maneuver far beyond their initial orbits.

  17. Quantitative changes in proteins responsible for flavonoid and anthocyanin biosynthesis in strawberry fruit at different ripening stages: A targeted quantitative proteomic investigation employing multiple reaction monitoring.

    Song, Jun; Du, Lina; Li, Li; Kalt, Wilhelmina; Palmer, Leslie Campbell; Fillmore, Sherry; Zhang, Ying; Zhang, ZhaoQi; Li, XiHong

    2015-06-03

    To better understand the regulation of flavonoid and anthocyanin biosynthesis, a targeted quantitative proteomic investigation employing LC-MS with multiple reaction monitoring was conducted on two strawberry cultivars at three ripening stages. This quantitative proteomic workflow was improved through an OFFGEL electrophoresis to fractionate peptides from total protein digests. A total of 154 peptide transitions from 47 peptides covering 21 proteins and isoforms related to anthocyanin biosynthesis were investigated. The normalized protein abundance, which was measured using isotopically-labeled standards, was significantly changed concurrently with increased anthocyanin content and advanced fruit maturity. The protein abundance of phenylalanine ammonia-lyase; anthocyanidin synthase, chalcone isomerase; flavanone 3-hydroxylase; dihydroflavonol 4-reductase, UDP-glucose:flavonoid-3-O-glucosyltransferase, cytochrome c and cytochrome C oxidase subunit 2, was all significantly increased in fruit of more advanced ripeness. An interaction between cultivar and maturity was also shown with respect to chalcone isomerase. The good correlation between protein abundance and anthocyanin content suggested that a metabolic control point may exist for anthocyanin biosynthesis. This research provides insights into the process of anthocyanin formation in strawberry fruit at the level of protein concentration and reveals possible candidates in the regulation of anthocyanin formation during fruit ripening. To gain insight into the molecular mechanisms contributing to flavonoids and anthocyanin biosynthesis and regulation of strawberry fruit during ripening is challenging due to limited molecular biology tools and established hypothesis. Our targeted proteomic approach employing LC-MS/MS analysis and MRM technique to quantify proteins in relation to flavonoids and anthocyanin biosynthesis and regulation in strawberry fruit during fruit ripening is novel. The identification of peptides

  18. Parent-administered computer-assisted tutoring targeting letter-sound knowledge: Evaluation via multiple-baseline across three preschool students.

    DuBois, Matthew R; Volpe, Robert J; Burns, Matthew K; Hoffman, Jessica A

    2016-12-01

    Knowledge of letters sounds has been identified as a primary objective of preschool instruction and intervention. Despite this designation, large disparities exist in the number of letter sounds children know at school entry. Enhancing caregivers' ability to teach their preschool-aged children letter sounds may represent an effective practice for reducing this variability and ensuring that more children are prepared to experience early school success. This study used a non-concurrent multiple-baseline-across-participants design to evaluate the effectiveness of caregivers (N=3) delivering a computer-assisted tutoring program (Tutoring Buddy) targeting letter sound knowledge to their preschool-aged children. Visual analyses and effect size estimates derived from Percentage of All Non-Overlapping Data (PAND) statistics indicated consistent results for letter sound acquisition, as 6weeks of intervention yielded large effects for letter sound knowledge (LSK) across all three children. Large effect sizes were also found for letter sound fluency (LSF) and nonsense word fluency (NWF) for two children. All three caregivers rated the intervention as highly usable and were able to administer it with high levels of fidelity. Taken together, the results of the present study found Tutoring Buddy to be an effective, simple, and usable way for the caregivers to support their children's literacy development. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  19. Targeted Quantitation of Site-Specific Cysteine Oxidation in Endogenous Proteins Using a Differential Alkylation and Multiple Reaction Monitoring Mass Spectrometry Approach

    Held, Jason M.; Danielson, Steven R.; Behring, Jessica B.; Atsriku, Christian; Britton, David J.; Puckett, Rachel L.; Schilling, Birgit; Campisi, Judith; Benz, Christopher C.; Gibson, Bradford W.

    2010-01-01

    Reactive oxygen species (ROS) are both physiological intermediates in cellular signaling and mediators of oxidative stress. The cysteine-specific redox-sensitivity of proteins can shed light on how ROS are regulated and function, but low sensitivity has limited quantification of the redox state of many fundamental cellular regulators in a cellular context. Here we describe a highly sensitive and reproducible oxidation analysis approach (OxMRM) that combines protein purification, differential alkylation with stable isotopes, and multiple reaction monitoring mass spectrometry that can be applied in a targeted manner to virtually any cysteine or protein. Using this approach, we quantified the site-specific cysteine oxidation status of endogenous p53 for the first time and found that Cys182 at the dimerization interface of the DNA binding domain is particularly susceptible to diamide oxidation intracellularly. OxMRM enables analysis of sulfinic and sulfonic acid oxidation levels, which we validate by assessing the oxidation of the catalytic Cys215 of protein tyrosine phosphatase-1B under numerous oxidant conditions. OxMRM also complements unbiased redox proteomics discovery studies as a verification tool through its high sensitivity, accuracy, precision, and throughput. PMID:20233844

  20. MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

    Noelia Sanchez

    Full Text Available MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

  1. Data fusion for target tracking and classification with wireless sensor network

    Pannetier, Benjamin; Doumerc, Robin; Moras, Julien; Dezert, Jean; Canevet, Loic

    2016-10-01

    In this paper, we address the problem of multiple ground target tracking and classification with information obtained from a unattended wireless sensor network. A multiple target tracking (MTT) algorithm, taking into account road and vegetation information, is proposed based on a centralized architecture. One of the key issue is how to adapt classical MTT approach to satisfy embedded processing. Based on track statistics, the classification algorithm uses estimated location, velocity and acceleration to help to classify targets. The algorithms enables tracking human and vehicles driving both on and off road. We integrate road or trail width and vegetation cover, as constraints in target motion models to improve performance of tracking under constraint with classification fusion. Our algorithm also presents different dynamic models, to palliate the maneuvers of targets. The tracking and classification algorithms are integrated into an operational platform (the fusion node). In order to handle realistic ground target tracking scenarios, we use an autonomous smart computer deposited in the surveillance area. After the calibration step of the heterogeneous sensor network, our system is able to handle real data from a wireless ground sensor network. The performance of system is evaluated in a real exercise for intelligence operation ("hunter hunt" scenario).

  2. A general method for closed-loop inverse simulation of helicopter maneuver flight

    Wei WU

    2017-12-01

    Full Text Available Maneuverability is a key factor to determine whether a helicopter could finish certain flight missions successfully or not. Inverse simulation is commonly used to calculate the pilot controls of a helicopter to complete a certain kind of maneuver flight and to assess its maneuverability. A general method for inverse simulation of maneuver flight for helicopters with the flight control system online is developed in this paper. A general mathematical describing function is established to provide mathematical descriptions of different kinds of maneuvers. A comprehensive control solver based on the optimal linear quadratic regulator theory is developed to calculate the pilot controls of different maneuvers. The coupling problem between pilot controls and flight control system outputs is well solved by taking the flight control system model into the control solver. Inverse simulation of three different kinds of maneuvers with different agility requirements defined in the ADS-33E-PRF is implemented based on the developed method for a UH-60 helicopter. The results show that the method developed in this paper can solve the closed-loop inverse simulation problem of helicopter maneuver flight with high reliability as well as efficiency. Keywords: Closed-loop, Flying quality, Helicopters, Inverse simulation, Maneuver flight

  3. Towards Real-Time Maneuver Detection: Automatic State and Dynamics Estimation with the Adaptive Optimal Control Based Estimator

    Lubey, D.; Scheeres, D.

    control policy is zero for all times). In this paper, we relax this assumption on the nominal trajectory in order to allow for controlled nominal trajectories. This allows the estimator to be iterated to obtain a more accurate nonlinear solution for both the state and control estimates. Beyond these developments to the estimator, this paper also introduces a modified distance metric for maneuver detection. The original metric used in the OCBE only accounted for the estimated control and its uncertainty. This new metric accounts for measurement deviation and a priori state deviations, such that it accounts for all three major forms of uncertainty in orbit determination. This allows the user to understand the contributions of each source of uncertainty toward the total system mismodeling so that the user can properly account for them. Together these developments create an accurate orbit determination algorithm that is automated, robust to mismodeling, and capable of detecting and reconstructing the presence of mismodeling. These qualities make this algorithm a good foundation from which to approach the problem of real-time maneuver detection and reconstruction for Space Situational Awareness applications. This is further strengthened by the algorithm's general formulation that allows it to be applied to problems with an arbitrary target and observer.

  4. Minimum Propellant Low-Thrust Maneuvers near the Libration Points

    Marinescu, A.; Dumitrache, M.

    The impulse technique certainly can bring the vehicle on orbits around the libration points or close to them. The question that aries is, by what means can the vehicle arrive in such cases at the libration points? A first investigation carried out in this paper can give an answer: the use of the technique of low-thrust, which, in addition, can bring the vehicle from the libration points near to or into orbits around these points. This aspect is considered in this present paper where for the applications we have considered the transfer for orbits of the equidistant point L4 and of the collinear point L2, from Earth-moon system. This transfer maneuver can be used to insertion one satellite on libration points orbits. In Earth- moon system the points L 4 and L 5 because an vehicle in on of the equidistant points in quite stable and remains in its vicinity of perturbed, have potential interest for the establishment of transporder satellite for interplanetary tracking. In contrast an vehicle in one of the collinear points is quite instable and it will oscillate along the Earth-moon-axis at increasing amplitude and gradually escape from the libration point. Let use assume that a space vehicle equipped with a low-thrust propulsion is near a libration point L. We consider the planar motion in the restricted frame of the three bodies in the rotating system L, where the Earth-moon distance D=l. The unit of time T is period of the moon's orbit divided by 2 and multiplied by the square root of the quantity one plus the moon/Earth mass ratio, and the unit of mass is the Earth's mass. With these predictions the motion equatios of the vehicle equiped with a low-thrust propulsion installation in the linear approximation near the libration point, have been established. The parameters of the motion at the beginning and the end of these maneuvers are known, the variational problem has been formulated as a Lagrange type problem with fixed extremities. On established the differential

  5. Gas tonometry for evaluation of gastrointestinal mucosal perfusion: experimental models of trauma, shock and complex surgical maneuvers - Part 1

    Figueiredo Luiz Francisco Poli de

    2002-01-01

    Full Text Available Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by trauma, shock, sepsis and several complex surgical maneuvers. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, a common cause of death after trauma, sepsis or major surgeries. Monitoring gut perfusion during experiments may provide valuable insights over new interventions and therapies highly needed to reduce trauma and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in clinical and experimental models of trauma, shock and surgical maneuvers associated with abrupt hemodynamic changes, such as aortic occlusion and hepatic vascular exclusion. Next issue we will be presenting our experience with gas tonometry in experimental and clinical sepsis.

  6. Statistical study of overvoltages by maneuvering in switches in high voltage using EMTP-RV

    Dominguez Herrera, Diego Armando

    2013-01-01

    The transient overvoltages produced by maneuvering of switches are studied in a statistical way and through a variation the sequential closing times of switches in networks larger than 230 kV. This study is performed according to time delays and typical deviation ranges, using the tool EMTP- RV (ElectroMagnetic Trasient Program Restructured Version). A conceptual framework related with the electromagnetic transients by maneuver is developed in triphasic switches installed in nominal voltages higher than 230 kV. The methodology established for the execution of statistical studies of overvoltages by switch maneuver is reviewed and evaluated by simulating two fictitious cases in EMTP-RV [es

  7. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    Teguh, David N.; Levendag, Peter C.; Voet, Peter W.J.; Al-Mamgani, Abrahim; Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S.; Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2011-01-01

    . Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

  8. Abundant and diverse clustered regularly interspaced short palindromic repeat spacers in Clostridium difficile strains and prophages target multiple phage types within this pathogen.

    Hargreaves, Katherine R; Flores, Cesar O; Lawley, Trevor D; Clokie, Martha R J

    2014-08-26

    Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an

  9. Auger electron emitter against multiple myeloma - targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4'-thio-2'-deoxyuridine

    Morgenroth, Agnieszka; Dinger, Cornelia; Zlatopolskiy, Boris D.; Al-Momani, Ehab; Glatting, Gerhard; Mottaghy, Felix M.; Reske, Sven N.

    2011-01-01

    Introduction: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue 125 I-labeled 5-iodo-4'-thio-2'-deoxyuridine ([ 125 I]ITdU). Methods: Cellular uptake and DNA incorporation of [ 125 I]ITdU were determined in fluorodeoxyuridine-pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [ 125 I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [ 125 I]ITdU was proven by clonogenic assay. Results: [ 125 I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [ 125 I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [ 125 I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [ 125 I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. Conclusion: These studies may provide a novel treatment strategy for overcoming

  10. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    Teguh, David N. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Levendag, Peter C., E-mail: p.levendag@erasmusmc.nl [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Voet, Peter W.J.; Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S. [Elekta-CMS Software, Maryland Heights, MO 63043 (United States); Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2011-11-15

    . Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

  11. Boswellic acid suppresses growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model through modulation of multiple targets.

    Byoungduck Park

    Full Text Available Pancreatic cancer (PaCa is one of the most lethal cancers, with an estimated 5-year survival of <5% even when patients are given the best treatment available. In addition, these treatments are often toxic and expensive, thus new agents which are safe, affordable and effective are urgently needed. We describe here the results of our study with acetyl-11-keto-β-boswellic acid (AKBA, an agent obtained from an Ayurvedic medicine, gum resin of Boswellia serrata. Whether AKBA has an activity against human PaCa, was examined in in vitro models and in an orthotopic nude mouse model of PaCa. We found that AKBA inhibited the proliferation of four different PaCa cell lines (AsPC-1, PANC-28, and MIA PaCa-2 with K-Ras and p53 mutations, and BxPC-3 with wild-type K-Ras and p53 mutation. These effects correlated with an inhibition of constitutively active NF-κB and suppression of NF-κB regulating gene expression. AKBA also induced apoptosis, and sensitized the cells to apoptotic effects of gemcitabine. In the orthotopic nude mouse model of PaCa, p.o. administration of AKBA alone (100 mg/kg significantly inhibited the tumor growth; this activity was enhanced by gemcitabine. In addition, AKBA inhibited the metastasis of the PaCa to spleen, liver, and lungs. This correlated with decreases in Ki-67, a biomarker of proliferation, and CD31, a biomarker of microvessel density, in the tumor tissue. AKBA produced significant decreases in the expression of NF-κB regulating genes in the tissues. Immunohistochemical analysis also showed AKBA downregulated the expression of COX-2, MMP-9, CXCR4, and VEGF in the tissues. Overall these results demonstrate that AKBA can suppress the growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model that correlates with modulation of multiple targets.

  12. Modern Estimation Techniques and Optimal Maneuver Targeting for Autonomous Optical Navigation around Small Bodies

    National Aeronautics and Space Administration — Autonomous Optical Navigation (AON) allows for significant advances in spacecraft navigation accuracy around small bodies located far from Earth, such as asteroids...

  13. The Dix-Hallpike test and the canalith repositioning maneuver.

    Viirre, Erik; Purcell, Ian; Baloh, Robert W

    2005-01-01

    The Dix-Hallpike test and the canalith repositioning maneuver (CRM) are used to diagnose and treat benign positional vertigo (BPV). Dix-Hallpike is the standard procedure for diagnosis of BPV, but if the horizontal canal is not tested for BPV and the Dix-Hallpike is only carried out once, the condition may not be diagnosed and appropriately treated. We describe our method of testing for BPV and treating it with CRM. The Dix-Hallpike test involves rapidly moving the patient from a sitting position to "head hanging," where the patient's head is at least 10 degrees below horizontal. This is performed initially for the posterior semicircular canals. If these movements fail to elicit vertigo and nystagmus, tests of the horizontal semicircular canals are performed by laying the patient on each side. Importantly, if there is no vertigo or nystagmus elicited by testing the horizontal semi-circular canals, the posterior semicircular canals are tested again. It appears that being held in the head hanging positions and then left and right lateral positions will often allow the canaliths to collect such that the Dix-Hallpike test will become positive. Failure to repeat the tests of the posterior semicircular canals may result in a falsely negative test. Testing the horizontal canals and repeating the Dix-Hallpike test will reduce the likelihood of patients undergoing extra testing or other consequences of misdiagnosis. If, during any of this testing, a movement elicits vertigo or nystagmus, the appropriate CRM is then carried out.

  14. Combilift ideal for maneuvering oil and gas equipment

    Anon.

    2009-07-15

    This article described an innovative forklift that responds to the oil industry's need for a safer, better and easier way to move long tubular products that cannot be carried high in the air. The Gator Jaw is a duplex pipe clamp attachment that secures to the Combilift forklift carriage. The clamp arm can be hydraulically moved upwards to allow the operator full use of the forks without interference from the hold down arm. The Combilift's platform is ideal for maneuvering oil and gas equipment close to the ground. Since it can travel sideways, the length of the load is not critical. The Gator Jaw's unique design makes it possible for one forklift to handle both skids and pallets. The C-Series product extends to the subsea oil and gas industry, which works with long loads such as oil drilling tools and pipe. The benefits include safer product handling, significant space savings, increased productivity and versatile indoor and outdoor use. The machines are available with a fuel-efficient liquefied petroleum gas (LPG) or diesel engine. 1 fig.

  15. Space shuttle orbit maneuvering engine reusable thrust chamber program

    Senneff, J. M.

    1975-01-01

    Reusable thrust chamber and injector concepts were evaluated for the space shuttle orbit maneuvering engine (OME). Parametric engine calculations were carried out by computer program for N2O4/amine, LOX/amine and LOX/hydrocarbon propellant combinations for engines incorporating regenerative cooled and insulated columbium thrust chambers. The calculation methods are described including the fuel vortex film cooling method of combustion gas temperature control, and performance prediction. A method of acceptance of a regeneratively cooled heat rejection reduction using a silicone oil additive was also demonstrated by heated tube heat transfer testing. Regeneratively cooled thrust chamber operation was also demonstrated where the injector was characterized for the OME application with a channel wall regenerative thrust chamber. Bomb stability testing of the demonstration chambers/injectors demonstrated recovery for the nominal design of acoustic cavities. Cavity geometry changes were also evaluated to assess their damping margin. Performance and combustion stability was demonstrated of the originally developed 10 inch diameter combustion pattern operating in an 8 inch diameter thrust chamber.

  16. Spacecraft Attitude Tracking and Maneuver Using Combined Magnetic Actuators

    Zhou, Zhiqiang

    2010-01-01

    The accuracy of spacecraft attitude control using magnetic actuators only is low and on the order of 0.4-5 degrees. The key reason is that the magnetic torque is two-dimensional and it is only in the plane perpendicular to the magnetic field vector. In this paper novel attitude control algorithms using the combination of magnetic actuators with Reaction Wheel Assembles (RWAs) or other types of actuators, such as thrusters, are presented. The combination of magnetic actuators with one or two RWAs aligned with different body axis expands the two-dimensional control torque to three-dimensional. The algorithms can guarantee the spacecraft attitude and rates to track the commanded attitude precisely. A design example is presented for Nadir pointing, pitch and yaw maneuvers. The results show that precise attitude tracking can be reached and the attitude control accuracy is comparable with RWAs based attitude control. The algorithms are also useful for the RWAs based attitude control. When there are only one or two workable RWAs due to RWA failures, the attitude control system can switch to the control algorithms for the combined magnetic actuators with the RWAs without going to the safe mode and the control accuracy can be maintained.

  17. Open Platform for Limit Protection with Carefree Maneuver Applications

    Jeram, Geoffrey J.

    2004-01-01

    This Open Platform for Limit Protection guides the open design of maneuver limit protection systems in general, and manned, rotorcraft, aerospace applications in particular. The platform uses three stages of limit protection modules: limit cue creation, limit cue arbitration, and control system interface. A common set of limit cue modules provides commands that can include constraints, alerts, transfer functions, and friction. An arbitration module selects the "best" limit protection cues and distributes them to the most appropriate control path interface. This platform adopts a holistic approach to limit protection whereby it considers all potential interface points, including the pilot's visual, aural, and tactile displays; and automatic command restraint shaping for autonomous limit protection. For each functional module, this thesis guides the control system designer through the design choices and information interfaces among the modules. Limit cue module design choices include type of prediction, prediction mechanism, method of critical control calculation, and type of limit cue. Special consideration is given to the nature of the limit, particularly the level of knowledge about it, and the ramifications for limit protection design, especially with respect to intelligent control methods such as fuzzy inference systems and neural networks.

  18. Spacecraft Attitude Tracking and Maneuver Using Combined Magnetic Actuators

    Zhou, Zhiqiang

    2012-01-01

    A paper describes attitude-control algorithms using the combination of magnetic actuators with reaction wheel assemblies (RWAs) or other types of actuators such as thrusters. The combination of magnetic actuators with one or two RWAs aligned with different body axis expands the two-dimensional control torque to three-dimensional. The algorithms can guarantee the spacecraft attitude and rates to track the commanded attitude precisely. A design example is presented for nadir-pointing, pitch, and yaw maneuvers. The results show that precise attitude tracking can be reached and the attitude- control accuracy is comparable with RWA-based attitude control. When there are only one or two workable RWAs due to RWA failures, the attitude-control system can switch to the control algorithms for the combined magnetic actuators with the RWAs without going to the safe mode, and the control accuracy can be maintained. The attitude-control algorithms of the combined actuators are derived, which can guarantee the spacecraft attitude and rates to track the commanded values precisely. Results show that precise attitude tracking can be reached, and the attitude-control accuracy is comparable with 3-axis wheel control.

  19. Tactical approach to maneuvering within the chemical contamination labyrinth

    Joseph, T.W. [Department of Energy, Oak Ridge, TN (United States)

    1990-12-31

    The Department of Energy (DOE) recognized the need and accepts the responsibility for understanding the reality and mitigating the consequence of the complex chemical contamination legacy it inherited as well as controlling, reducing, and eliminating extant emissions and effluents. The key to maneuvering through this complicated and multifaceted labyrinth of concerns, from which a meaningful, high quality, and cost-effective restoration/mitigation machine is then set in motions, is the ability to perform accurate, factual, and explicit health and environmental/ecological risk assessments. Likewise, the common denominator for carrying out this essential task is to have access to comprehensive and reliable data of known quality with which to perform those analyses. DOE is committed to identifying the data universe; to technically scrutinize and ensure the quality of that data; to develop efficient and cost-effective means to maximize the handling, utilization, and sharing of that universe; and to undertake those assessments. DOE views this as an effort that can only be accomplished through a merging of the technical excellence that exists within federal and state agencies, academia, and industry. The task at hand is so large that only by integrating that intelligence base can we hope to accomplish the goals of establishing meaningful standards, developing functional and effective solutions, and providing quality guidance at a national scale.

  20. Steering characteristic of an articulated bus under quasi steady maneuvering

    Ubaidillah, Setiawan, Budi Agus; Aridharma, Airlangga Putra; Lenggana, Bhre Wangsa; Caesar, Bernardus Placenta Previo

    2018-02-01

    Articulated buses have been being preferred as public transportation modes due to their operational capacity. Therefore, passenger safety must be the priority of this public service vehicle. This research focused on the analytical approach of steering characteristics of an articulated bus when it maneuvered steadily. Such turning condition could be referred as a stability parameter of the bus for preliminary handling assessment. The analytical approach employed kinematics relationship between front and rear bodies as well as steering capabilities. The quasi steady model was developed to determine steering parameters such as turning radius, oversteer, and understeer. The mathematical model was useful for determining both coefficients of understeer and oversteer. The dimension of articulated bus followed a commonly used bus as utilized in Trans Jakarta busses. Based on the simulation, for one minimum center of the body, the turning radius was calculated about 8.8 m and 7.6 m at steady turning speed of 10 km/h. In neutral condition, the minimum road radius should be 6.5 m at 10 km/h and 6.9 m at 40 km/h. For two centers of the body and oversteer condition, the front body has the turning radius of 8.8 m, while, the rear body has the turning radius of 9.8 m at both turning speeds of 40 km/h. The other steering parameters were discussed accordingly.

  1. A safe-repositioning maneuver for the management of benign paroxysmal positional vertigo: Gans vs. Epley maneuver; a randomized comparative clinical trial.

    Saberi, Alia; Nemati, Shadman; Sabnan, Salah; Mollahoseini, Fatemeh; Kazemnejad, Ehsan

    2017-08-01

    Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo. Some repositioning maneuvers have been described for its management. The aim of this study was comparing the therapeutic effect of Epley and Gans maneuvers in BPPV. This randomized clinical trial was performed from September to December 2015. 73 patients with true vertigo diagnosed as BPPV enrolled the study. They randomly assigned in quadripartite blocks to modified Epley maneuver group (E) or Gans maneuver group (G). 1 day and 1 week after intervention, the objective and subjective responses to treatment were assessed. Statistical analysis was performed using the Chi-square test and regression model in the SPSS software version 21. Thirty patients enrolled each group with a mean age of 46.9 ± 13.4 (E group) and 46.7 ± 7.5 year (G group). 23.3 % of E group and 26.7 % of G group were men (p = 0.766). In E and G groups in the first day, subjective outcomes revealed 86.7 and 60 % rate of success (p = 0.02); and 86.7 and 56.7 % of patients exhibited objective improvement, respectively (p = 0.01). After 1 week, the subjective and objective outcomes revealed improvement among 70 % of E group and 46.7 % of G group (p = 0.067). The only complication with significant difference was cervical pain with a higher rate in E group (23.3 vs. 0.0 %, p = 0.005). These results revealed the similar long-term efficacy of Epley and Gans maneuver for the treatment of BPPV. Cervical pain was most frequent complication of Epley maneuver.

  2. Efficacy of Epley’s Maneuver in Treating BPPV Patients: A Prospective Observational Study

    Sushil Gaur

    2015-01-01

    Full Text Available Vertigo and balance disorders are among the most common symptoms encountered in patients who visit ENT outpatient department. This is associated with risk of falling and is compounded in elderly persons with other neurologic deficits and chronic medical problems. BPPV is the most common cause of peripheral vertigo. BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact, and medical costs. The objective of Epley’s maneuver, which is noninvasive, inexpensive, and easily administered, is to move the canaliths out of the canal to the utricle where they no longer affect the canal dynamics. Our study aims to analyze the response to Epley’s maneuver in a series of patients with posterior canal BPPV and compares the results with those treated exclusively by medical management alone. Even though many studies have been conducted to prove the efficacy of this maneuver, this study reinforces the validity of Epley’s maneuver by comparison with the medical management.

  3. Importance of back blow maneuvers in a 6 month old patient with sudden upper airway obstruction

    Pinar Gencpinar

    2015-12-01

    Full Text Available Foreign body aspiration in children under four years old is one of the most frequently observed reasons for accident related deaths. It is more common in this age group due to inadequate swallowing functions and exploration of objects with the mouth. The most frequently encountered foreign bodies are food and toy parts. Life threatening complete laryngeal obstruction is rarely observed. Dyspnea, hypersalivation, cough and cyanosis can be seen. The basic and life-saving treatment approach is complete removal of foreign body maneuvers in the sudden onset of total obstruction. Here we report a six-month old male, who ingested a foreign body and was treated with back blow maneuvers successfully. In this case we emphasized the importance of back blow maneuvers. Keywords: Upper airway obstruction, Child, Back blows maneuvers

  4. A Computer Simulation of the System-Wide Effects of Parallel-Offset Route Maneuvers

    Lauderdale, Todd A.; Santiago, Confesor; Pankok, Carl

    2010-01-01

    Most aircraft managed by air-traffic controllers in the National Airspace System are capable of flying parallel-offset routes. This paper presents the results of two related studies on the effects of increased use of offset routes as a conflict resolution maneuver. The first study analyzes offset routes in the context of all standard resolution types which air-traffic controllers currently use. This study shows that by utilizing parallel-offset route maneuvers, significant system-wide savings in delay due to conflict resolution of up to 30% are possible. It also shows that most offset resolutions replace horizontal-vectoring resolutions. The second study builds on the results of the first and directly compares offset resolutions and standard horizontal-vectoring maneuvers to determine that in-trail conflicts are often more efficiently resolved by offset maneuvers.

  5. Pulsed Electrogasdynamic Thruster for Attitude Control and Orbit Maneuver, Phase I

    National Aeronautics and Space Administration — A new pulsed electric thruster, named "pulsed electrogasdynamic thruster," for attitude control and orbit maneuver is proposed. In this thruster, propellant gas is...

  6. The application of the random regret minimization model to drivers’ choice of crash avoidance maneuvers

    Kaplan, Sigal; Prato, Carlo Giacomo

    This study explores the plausibility of regret minimization as behavioral paradigm underlying the choice of crash avoidance maneuvers. Alternatively to previous studies that considered utility maximization, this study applies the random regret minimization (RRM) model while assuming that drivers ...

  7. The application of the random regret minimization model to drivers’ choice of crash avoidance maneuvers

    Kaplan, Sigal; Prato, Carlo Giacomo

    2012-01-01

    This study explores the plausibility of regret minimization as behavioral paradigm underlying the choice of crash avoidance maneuvers. Alternatively to previous studies that considered utility maximization, this study applies the random regret minimization (RRM) model while assuming that drivers ...

  8. Determination of the optimal conditions for inclination maneuvers using a Swing-by

    Moura, O.; Celestino, C. C.; Prado, A. F. B. A.

    2018-05-01

    The search for methods to reduce the fuel consumption in orbital transfers is something relevant and always current in astrodynamics. Therefore, the maneuvers assisted by the gravity, also called Swing-by maneuvers, can be an advantageous option to save fuel. The proposal of the present research is to explore the influence of some parameters in a Swing-by of an artificial satellite orbiting a planet with one of the moons of this mother planet, with the goal of changing the inclination of the artificial satellite around the main body of the system. The fuel consumption of this maneuver is compared with the required consumption to perform the same change of inclination using the classical approach of impulsive maneuvers.

  9. The Rapier or the Club: The Relationship between Attrition and Maneuver Warfare

    Springman, Jeffrey A

    2006-01-01

    ...? This project compares the relationship between attrition and maneuver warfare. The study considers whether there are times when wars of attrition should be fought, and whether there are conditions that force wars of attrition...

  10. Use of Lung Opening Maneuver in Patients with Acute Respiratory Failure After Cardiosurgical Operations

    A. A. Yeremenko

    2006-01-01

    Full Text Available Postoperative respiratory failure is a most common complication and a main cause of postoperative death. The lung opening maneuver is a most effective method of respiratory therapy for this syndrome.Objective. To evaluate the impact of recruiting maneuver on gas exchange parameters, the biomechanical properties of the lung, and hemodynamic parameters. To determine whether the lung opening maneuver can be fully performed in patients undergoing cardiac surgery.Materials and methods. The study covered 19 patients aged 53 to 70 years who had postoperative failure. The indication for the recruiting maneuver was a decrease in the oxygenation index below 250 mm Hg during assisted ventilation (AV with FiO2>0.5, an inspiratory-expira-tory phase ratio of 1:1 to 3:1, and a positive end-expiratory pressure of 5—10 cm H2O.Results. A decrease in the oxygenation index to 139±36 mm Hg was observed before the recruiting maneuver was applied. Cd;n. averaged 41.1±8.4 ml/cm H2O. After use of the recruiting maneuver, there were increases in the oxygenation index up to 371±121 mm Hg and in Cd;n. up to 64.3±10 ml/cm H2O in all the patients. When the recruiting maneuver was employed, 14 patients were observed to have elevated blood pressures corrected with a vasopressor. One patient developed pneumothorax that was drained in proper time.Conclusion. The application of the lung opening maneuver leads to a considerable improvement of gas exchange parameters and lung mechanical properties.

  11. CFD Analysis of a Maneuvering F/A-18E Super Hornet

    2016-10-12

    tools for aircraft, ships, and radio - frequency antenna design and analysis. The resulting program is called the Computational Research and Engineering...accurately predicting the forces and moments on the F/A-18E Super Hornet while performing several complicated maneuvers. Past F/A-18E computational studies... predicting the forces and moments on the F/A-18E Super Hornet while performing several complicated maneuvers. Past F/A-18E computational studies have

  12. Know Before You Do: Anticipating Maneuvers via Learning Temporal Driving Models

    2015-04-01

    features/index.htm. Accessed: 2014-09-30. [3] Google self driving car . http://en.wikipedia.org/wiki/ Google driverless car . Accessed: 2014-10-11. [4...and outside the car , GPS, and speed information, with lane and driving maneuver annotations. II. RELATED WORK Assistive features for vehicles . Recent...made driving safer over the last decade. They prepare vehicles for unsafe road conditions and alert drivers if they perform a dangerous maneuver

  13. A general method for closed-loop inverse simulation of helicopter maneuver flight

    Wei WU

    2017-01-01

    Maneuverability is a key factor to determine whether a helicopter could finish certain flight missions successfully or not. Inverse simulation is commonly used to calculate the pilot controls of a helicopter to complete a certain kind of maneuver flight and to assess its maneuverability. A general method for inverse simulation of maneuver flight for helicopters with the flight control system online is developed in this paper. A general mathematical describing function is established to provid...

  14. A conceptual study of the use of a particle bed reactor nuclear propulsion module for the orbital maneuvering vehicle

    Malloy, J.; Potekhen, D.

    1989-01-01

    This paper examines the use of a particle bed reactor nuclear engine for direct thrust in a spacecraft based on the NASA/TRW orbital maneuvering vehicle (OMV). It presents the conceptual design of a 500 lb thrust engine that matches critical design features of the existing OMV bi-propellant propulsion system. This application contrasts with the usual tendency to consider a nuclear heat source either for high thrust direct propulsion or as a power source for electric propulsion. A nuclear propulsion module adapted to the OMV could potentially accomplish several Department of Defense missions, such as multiple round trips from a space-based support platform at 280 NM to service a constellation of satellites orbiting at 1800 NM

  15. Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells.

    Jeanine Schibler

    Full Text Available Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266, using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog. In primary human MM samples, increased glycolytic gene expression correlated with poorer overall and event-free survival outcomes. Notably, stem-like cells showed increased mitochondrial mass, rhodamine 123 accumulation, and orthodox mitochondrial configuration while more condensed mitochondria were noted in the CD138high cells. Glycolytic inhibitor 2-deoxyglucose (2-DG induced ER stress as detected by qPCR (BiP, ATF4 and immunoblotting (BiP, CHOP and increased dihydroethidium probe oxidation both CD138low and CD138high cells. Treatment with a mitochondrial-targeting agent decyl-triphenylphosphonium (10-TPP increased intracellular steady-state pro-oxidant levels in stem-like and mature MM cells. Furthermore, 10-TPP mediated increases in mitochondrial oxidant production were suppressed by ectopic expression of manganese superoxide dismutase. Relative to 2-DG or 10-TPP alone, 2-DG plus 10-TPP combination showed increased caspase 3 activation in MM cells with minimal toxicity to the normal hematopoietic progenitor cells. Notably, treatment with polyethylene glycol conjugated catalase significantly reduced 2-DG and/or 10-TPP-induced apoptosis of MM cells. Also, the combination of 2-DG with 10-TPP decreased clonogenic survival of MM cells. Taken together, this study provides a novel strategy of metabolic oxidative stress-induced cytotoxicity of MM

  16. An Analytical Solution for Yaw Maneuver Optimization on the International Space Station and Other Orbiting Space Vehicles

    Dobrinskaya, Tatiana

    2015-01-01

    This paper suggests a new method for optimizing yaw maneuvers on the International Space Station (ISS). Yaw rotations are the most common large maneuvers on the ISS often used for docking and undocking operations, as well as for other activities. When maneuver optimization is used, large maneuvers, which were performed on thrusters, could be performed either using control moment gyroscopes (CMG), or with significantly reduced thruster firings. Maneuver optimization helps to save expensive propellant and reduce structural loads - an important factor for the ISS service life. In addition, optimized maneuvers reduce contamination of the critical elements of the vehicle structure, such as solar arrays. This paper presents an analytical solution for optimizing yaw attitude maneuvers. Equations describing pitch and roll motion needed to counteract the major torques during a yaw maneuver are obtained. A yaw rate profile is proposed. Also the paper describes the physical basis of the suggested optimization approach. In the obtained optimized case, the torques are significantly reduced. This torque reduction was compared to the existing optimization method which utilizes the computational solution. It was shown that the attitude profiles and the torque reduction have a good match for these two methods of optimization. The simulations using the ISS flight software showed similar propellant consumption for both methods. The analytical solution proposed in this paper has major benefits with respect to computational approach. In contrast to the current computational solution, which only can be calculated on the ground, the analytical solution does not require extensive computational resources, and can be implemented in the onboard software, thus, making the maneuver execution automatic. The automatic maneuver significantly simplifies the operations and, if necessary, allows to perform a maneuver without communication with the ground. It also reduces the probability of command

  17. [Effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection].

    Fan, Yuan-hua; Liu, Yuan-fei; Zhu, Hua-yong; Zhang, Min

    2012-02-01

    To evaluate effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection, based on the protective pulmonary ventilation strategy. Ninety-seven cases with severe pulmonary infection admitted to intensive care unit (ICU) of Ganzhou City People's Hospital undergoing mechanical ventilation were involved. Volume controlled ventilation mode with small tidal volume (8 ml/kg) and positive end-expiratory pressure (PEEP) of 6 cm H(2)O [1 cm H(2)O = 0.098 kPa] was conducted. Each patient underwent recruitment maneuver in supine position and then in prone position [PEEP 20 cm H(2)O+pressure control (PC) 20 cm H(2)O]. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation [SpO(2)] and blood gas analysis data were recorded before and after recruitment maneuver in either position. A double-lumen venous catheter was inserted into internal jugular vein or subclavian vein, and a pulse index contour cardiac output (PiCCO) catheter was introduced into femoral artery. Cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI), intra-thoracic blood volume index (ITBVI), extra vascular lung water index (EVLWI), global end-diastolic volume index (GEDVI), global ejection fraction (GEF), stroke volume variation (SVV) and central vein pressure (CVP) were monitored. (1) Compared with data before recruitment maneuver, there were no significant differences in HR and MAP after supine position and prone position recruitment maneuver, but significant differences in SpO(2) were found between before and after recruitment maneuver when patients' position was changed (supine position: 0.954 ± 0.032 vs. 0.917 ± 0.025, P recruitment maneuver (P recruitment maneuver, CI [L×min(-1)×m(-2)], SVI (ml/m(2)), GEDVI (ml/m(2)) and GEF were decreased significantly during recruitment maneuver (supine position: CI 3.2 ± 0.4 vs. 3.8 ± 0.6, SVI 32.4 ± 5.6 vs. 38.8 ± 6.5, GEDVI 689 ± 44 vs. 766 ± 32, GEF 0.267 ± 0

  18. Signal and data processing of small targets 1990; Proceedings of the Meeting, Orlando, FL, Apr. 16-18, 1990

    Drummond, Oliver E.

    Various papers on signal and data processing of small targets are presented. Individual topics addressed include: clutter rejection using multispectral processing, new sensor for automatic guidance, Doppler domain localized generalized-likelihood-ratio detector, linear filter for resolution of point sources, analysis of order-statistic filters for robust detection, distribution functions for additive Gaussian and gamma noise, temperature discrimination of closely space objects, knowledge-based tracking algorithm, detecting and tracking low-observable targets using IR, weak target detection using the entropy concept, measurement-based neural-net multitarget tracker, object-track closed-form solution in angle space, passive-sensor data association for tracking. Also discussed are: application of MHT to dim moving targets, automatic static covariance analysis with mathematica, neural network implementation of plot/track association, application of Bayesian networks to multitarget tracking, tracking clusters and extended objects with multiple sensors, target tracking by human operator, finite impulse response estimator, multitarget tracking using an extended Kalman filter, maneuvering target tracking using a two-state model algorithm, mixture reduction algorithms for target tracking in clutter, scene interpretation approach to high-level target tracking.

  19. Prevention of shoulder dystocia: A randomized controlled trial to evaluate an obstetric maneuver.

    Poujade, Olivier; Azria, Elie; Ceccaldi, Pierre-François; Davitian, Carine; Khater, Carine; Chatel, Paul; Pernin, Emilie; Aflak, Nizar; Koskas, Martin; Bourgeois-Moine, Agnès; Hamou-Plotkine, Laurence; Valentin, Morgane; Renner, Jean-Paul; Roy, Carine; Estellat, Candice; Luton, Dominique

    2018-08-01

    Shoulder dystocia is a major obstetric emergency defined as a failure of delivery of the fetal shoulder(s). This study evaluated whether an obstetric maneuver, the push back maneuver performed gently on the fetal head during delivery, could reduce the risk of shoulder dystocia. We performed a multicenter, randomized, single-blind trial to compare the push back maneuver with usual care in parturient women at term. The primary outcome, shoulder dystocia, was considered to have occurred if, after delivery of the fetal head, any additional obstetric maneuver, beginning with the McRoberts maneuver, other than gentle downward traction and episiotomy was required. We randomly assigned 522 women to the push back maneuver group (group P) and 523 women to the standard vaginal delivery group (group S). Finally, 473 women assigned to group P and 472 women assigned to group S delivered vaginally. The rate of shoulder dystocia was significantly lower in group P (1·5%) than in group S (3·8%) (odds ratio [OR] 0·38 [0·16-0·92]; P = 0·03). After adjustment for predefined main risk factors, dystocia remained significantly lower in group P than in group S. There were no significant between-group differences in neonatal complications, including brachial plexus injury, clavicle fracture, hematoma and generalized asphyxia. In this trial in 945 women who delivered vaginally, the push back maneuver significantly decreased the risk of shoulder dystocia, as compared with standard vaginal delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Five surgical maneuvers on nasal mucosa movement in cleft palate repair: A cadaver study.

    Nguyen, Dennis C; Patel, Kamlesh B; Parikh, Rajiv P; Skolnick, Gary B; Woo, Albert S

    2016-06-01

    This biomechanical study aims to characterize the nasal mucosa during palatoplasty, thereby describing the soft tissue attachments at different zones and quantifying movement following their release. Palatal nasal mucosa was exposed and divided in the midline in 10 adult cadaver heads. Five consecutive maneuvers were performed: (1) elevation of nasal mucosa off the maxilla, (2) dissection of nasal mucosa from soft palate musculature, (3) separation of nasal mucosa from palatine aponeurosis, (4) release of mucosa at the pterygopalatine junction, and (5) mobilization of vomer flaps. The mucosal movements across the midline at the midpalate (MP) and posterior nasal spine (PNS) following each maneuver were measured. At the MP, maneuvers 1-4 cumulatively provided 3.8 mm (36.9%), 4.9 mm (47.6%), 6.1 mm (59.2%), and 10.3 mm, respectively. Vomer flap (10.5 mm) elevation led to mobility equivalent to that of maneuvers 1-4 (p = 0.72). At the PNS, cumulative measurements after maneuvers 1-4 were 1.3 mm (10%), 2.4 mm (18.6%), 5.7 mm (44.2%), and 12.9 mm. Here, vomer flaps (6.5 mm) provided less movement (p < 0.001). Maneuver 4 yielded the greatest amount of movement of the lateral nasal mucosa at both MP (4.2 mm, 40.8%) and PNS (7.2 mm, 55.8%). At the MP, complete release of the lateral nasal mucosa achieves as much movement as the vomer flap. At the hard-soft palate junction, the maneuvers progressively add to the movement of the lateral nasal mucosa. The most powerful step is release of attachments along the posterior aspect of the medial pterygoid. Published by Elsevier Ltd.

  1. Mechanical Constraints on Flight at High Elevation Decrease Maneuvering Performance of Hummingbirds.

    Segre, Paolo S; Dakin, Roslyn; Read, Tyson J G; Straw, Andrew D; Altshuler, Douglas L

    2016-12-19

    High-elevation habitats offer ecological advantages including reduced competition, predation, and parasitism [1]. However, flying organisms at high elevation also face physiological challenges due to lower air density and oxygen availability [2]. These constraints are expected to affect the flight maneuvers that are required to compete with rivals, capture prey, and evade threats [3-5]. To test how individual maneuvering performance is affected by elevation, we measured the free-flight maneuvers of male Anna's hummingbirds in a large chamber translocated to a high-elevation site and then measured their performance at low elevation. We used a multi-camera tracking system to identify thousands of maneuvers based on body position and orientation [6]. At high elevation, the birds' translational velocities, accelerations, and rotational velocities were reduced, and they used less demanding turns. To determine how mechanical and metabolic constraints independently affect performance, we performed a second experiment to evaluate flight maneuvers in an airtight chamber infused with either normoxic heliox, to lower air density, or nitrogen, to lower oxygen availability. The hypodense treatment caused the birds to reduce their accelerations and rotational velocities, whereas the hypoxic treatment had no significant effect on maneuvering performance. Collectively, these experiments reveal how aerial maneuvering performance changes with elevation, demonstrating that as birds move up in elevation, air density constrains their maneuverability prior to any influence of oxygen availability. Our results support the hypothesis that changes in competitive ability at high elevations are the result of mechanical limits to flight performance [7]. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Target preparation

    Hinn, G.M.

    1984-01-01

    A few of the more interesting of the 210 targets prepared in the Laboratory last year are listed. In addition the author continues to use powdered silver mixed with /sup 9,10/BeO to produce sources for accelerator radio dating of Alaskan and South Polar snow. Currently, he is trying to increase production by multiple sample processing. Also the author routinely makes 3 μg/cm 2 cracked slacked carbon stripper foils and is continuing research with some degree of success in making enriched 28 Si targets starting with the oxide

  3. Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

    Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.

    2015-01-01

    lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide......Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination...

  4. An Adaptive Algorithm of Maneuvering Targets Tracking Based on Maneuvering Frequency%基于机动频率自适应的目标跟踪算法

    任少伟; 王睿; 张平定

    2004-01-01

    利用观测新息在目标机动时发生变化的信息,设计了一种自适应的机动目标跟踪算法,通过对目标状态误差的估计,从而自适应的改变机动频率,使跟踪算法与目标的真实状态更接近,该算法具有运算量小、跟踪精度高、易于工程化实现的特点.

  5. Ship operation and failure mode analysis using a maneuver simulator

    Cabrerizo-Morales, Miguel Angel; Molina, Rafael; de los Santos, Francisco; Camarero, Alberto

    2013-04-01

    In a ship or floating structure operation the agents that contribute to the systems behaviour are not only those derived from fluid-structure interaction, but also the ones linked to mooring-control line set-up evolution and human interaction. Therefore, the analysis of such systems is affected by boundary conditions that change during a complete operation. Frequently, monitoring techniques in laboratory (model) and field (prototype) are based in different instrumental techniques adding difficulty to data comparison and, in some cases, inducing precision and repeatability errors. For this reason, the main aim of this study is to develop the methods and tools to achieve a deep knowledge of those floating systems and obtain capabilities to optimize their operationally thresholds. This abstract presents a methodology and an instrumental system applicable both in field and laboratory: SRECMOCOS Project (Small scale REal-time Caisson MOnitoring and COntrol System). SRECMOCOS compiles three modules. For the monitoring and control of the structure it has been developed a synchronized open and modular microcontroller-based electronic system that comprises sensors, to monitor agents and reactions, and actuators to perform pertinent actions after processing the sensors' data. A secondary objective has been to design and implement a global scaled simulator (1:22), at the 3D basin of The Harbour Research Lab at Technical University of Madrid, in which climatic agents and those derived from the rig/maneuvering setup and the structural design were included. The particular case of Campamento's drydock, in Algeciras Bay (Spain), has been used to apply and validate the methodology. SRECMOCOS Project conjugates control, monitoring and wireless communication systems in a real time basis, offering the possibility to register and simulate all the parameters involved in port operations. This approach offers a step forward into a monitoring strategy to be included in monitoring

  6. The influence of airway supporting maneuvers on glottis view in pediatric fiberoptic bronchoscopy

    Tarik Umutoglu

    2015-10-01

    Full Text Available ABSTRACTINTRODUCTION:Flexible fiber optic bronchoscopy is a valuable intervention for evaluation and management of respiratory diseases in both infants, pediatric and adult patients. The aim of this study is to investigate the influence of the airway supporting maneuvers on glottis view during pediatric flexible fiberoptic bronchoscopy.MATERIALS AND METHODS:In this randomized, controlled, crossover study; patients aged between 0 and 15 years who underwent flexible fiberoptic bronchoscopy procedure having American Society of Anesthesiologists I---II risk score were included. Patients having risk of difficult intubation, intubated or patients with tracheostomy, and patients with reduced neck mobility or having cautions for neck mobility were excluded from this study. After obtaining best glottic view at the neutral position, patients were positioned jaw trust with open mouth, jaw trust with teeth prottution, head tilt chin lift and triple airway maneuvers and best glottis scores were recorded.RESULTS:Total of 121 pediatric patients, 57 girls and 64 boys, were included in this study. Both jaw trust with open mouth and jaw trust with teeth prottution maneuvers improved the glottis view compared with neutral position (p 0.05. Head tilt chin lift and triple airway maneuvers improved glottis view when compared with both jaw trust with open mouth and jaw trust with teeth prottution maneuvers and neutral position (p 0.05.

  7. oVEMP as an objective indicator of successful repositioning maneuver.

    Asal, Samir; Sobhy, Osama; Balbaa, Amany

    Benign paroxysmal positioning vertigo (BPPV) is the most common peripheral vestibular disorder. Canalolithiasis in the posterior semi-circular canal is the most common underlying pathology that can be treated effectively by repositioning maneuvers. Our hypothesis suggested that successful maneuvers can lead to repositioning of dislodged otoconia to the utricle. Air conducted oVEMP, which is thought to originate from the contra-lateral utricular organ was measured in twenty patients with unilateral BPPV and we compared n1-p1 peak to peak amplitude of the affected ears in 3 separate intervals: on pre-treatment when typical nystagmus was confirmed, immediately after, and 1 week after repositioning maneuvers to assess change, if any, in amplitude. This study showed significant increase of oVEMP amplitude in the affected ears after successful repositioning maneuver that was more significant after 1 week. oVEMP can be used as a reliable objective test for ensuring a successful maneuver rather than subjective dependence on the patient's symptoms, which may be misleading due to a remission. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  8. A Comparison of Obstetric Maneuvers for the Acute Management of Shoulder Dystocia

    Hoffman, Matthew K; Bailit, Jennifer L; Branch, D. Ware; Burkman, Ronald T; Van Veldhusien, Paul; Lu, Li; Kominiarek, Michelle A.; Hibbard, Judith U; Landy, Helain J; Haberman, Shoshana; Wilkins, Isabelle; Gonzalez Quintero, Victor H; Gregory, Kimberly D; Hatjis, Christos G; Ramirez, Mildred M; Reddy, Uma M.; Troendle, James; Zhang, Jun

    2011-01-01

    Objective To assess the efficacy of obstetric maneuvers for resolving shoulder dystocia, and the effect that these maneuvers have on neonatal injury when shoulder dystocia occurs. Methods Using an electronic database encompassing 206,969 deliveries, we identified all women with a vertex fetus beyond 34 0/7 weeks of gestation who incurred a shoulder dystocia during the process of delivery. Women whose fetuses had a congenital anomaly and women with an antepartum stillbirth were excluded. Medical records of all cases were reviewed by trained abstractors. Cases involving neonatal injury (defined as brachial plexus injury, clavicular or humerus fracture, or hypoxic ischemic encephalopathy or intrapartum neonatal death attributed to the shoulder dystocia) were compared to those without injury. RESULTS Among 132,098 women who delivered a term cephalic liveborn fetus vaginally, 2,018 incurred a shoulder dystocia (1.5%), and 101 (5.2%) of these incurred a neonatal injury. Delivery of the posterior shoulder was associated with the highest rate of delivery when compared to other maneuvers (84.4% compared with 24.3% to 72.0% for other maneuvers; Pdystocia. The need for additional maneuvers was associated with higher rates of neonatal injury. PMID:21555962

  9. Automated low-thrust guidance for the orbital maneuvering vehicle

    Rose, Richard E.; Schmeichel, Harry; Shortwell, Charles P.; Werner, Ronald A.

    1988-01-01

    This paper describes the highly autonomous OMV Guidance Navigation and Control system. Emphasis is placed on a key feature of the design, the low thrust guidance algorithm. The two guidance modes, orbit change guidance and rendezvous guidance, are discussed in detail. It is shown how OMV will automatically transfer from its initial orbit to an arbitrary target orbit and reach a specified rendezvous position relative to the target vehicle.

  10. Ground Track Acquisition and Maintenance Maneuver Modeling for Low-Earth Orbit Satellite

    Byoung-Sun Lee

    1997-12-01

    Full Text Available This paper presents a comprehensive analytical approach for determining key maneuver parameters associated with the acquisition and maintenance of the ground track for a low-earth orbit. A livearized model relating changes in the drift rate of the ground track directly to changes in the orbital semi-major axis is also developed. The effect of terrestrial atmospheric drag on the semi-major axis is also explored, being quantified through an analytical expression for the decay rate as a function of density. The non-singular Lagrange planetary equations, further simplified for nearly circular orbits, provide the desired relationships between the corrective in-plane impulsive velocity increments and the corresponding effects on the orbit elements. The resulting solution strategy offers excellent insight into the dynamics affecting the timing, magnitude, and frequency of these maneuvers. Simulations are executed for the ground track acquisition and maintenance maneuver as a pre-flight planning and analysis.

  11. Associating crash avoidance maneuvers with driver attributes and accident characteristics: a mixed logit model approach

    Kaplan, Sigal; Prato, Carlo Giacomo

    2012-01-01

    from the key role of proactive and state-aware road users within the concept of sustainable safety systems, as well as from the key role of effective corrective maneuvers in the success of automated in-vehicle warning and driver assistance systems. Methods: The analysis is conducted by means of a mixed...... about the risks of driving under fatigue and distraction being comparable to the risks of driving under the influence of alcohol and drugs. Moreover, the results suggest the need to educate drivers about hazard perception, designing a forgiving infrastructure within a sustainable safety systems......Objective: The current study focuses on the propensity of drivers to engage in crash avoidance maneuvers in relation to driver attributes, critical events, crash characteristics, vehicles involved, road characteristics, and environmental conditions. The importance of avoidance maneuvers derives...

  12. Effect of Conflict Resolution Maneuver Execution Delay on Losses of Separation

    Cone, Andrew C.

    2010-01-01

    This paper examines uncertainty in the maneuver execution delay for data linked conflict resolution maneuvers. This uncertainty could cause the previously cleared primary conflict to reoccur or a secondary conflict to appear. Results show that the likelihood of a primary conflict reoccurring during a horizontal conflict resolution maneuver increases with larger initial turn-out angles and with shorter times until loss of separation. There is also a significant increase in the probability of a primary conflict reoccurring when the time until loss falls under three minutes. Increasing horizontal separation by an additional 1.5 nmi lowers the risk, but does not completely eliminate it. Secondary conflicts were shown to have a small probability of occurring in all tested configurations.

  13. Contingency Trajectory Design for a Lunar Orbit Insertion Maneuver Failure by the LADEE Spacecraft

    Genova, A. L.

    2014-01-01

    This paper presents results from a contingency trajectory analysis performed for the Lunar Atmosphere & Dust Environment Explorer (LADEE) mission in the event of a missed lunar-orbit insertion (LOI) maneuver by the LADEE spacecraft. The effects of varying solar perturbations in the vicinity of the weak stability boundary (WSB) in the Sun-Earth system on the trajectory design are analyzed and discussed. It is shown that geocentric recovery trajectory options existed for the LADEE spacecraft, depending on the spacecraft's recovery time to perform an Earth escape-prevention maneuver after the hypothetical LOI maneuver failure and subsequent path traveled through the Sun-Earth WSB. If Earth-escape occurred, a heliocentric recovery option existed, but with reduced science capacapability for the spacecraft in an eccentric, not circular near-equatorial retrograde lunar orbit.

  14. Analysis of effects of manhole covers on motorcycle driver maneuvers: a nonparametric classification tree approach.

    Chang, Li-Yen

    2014-01-01

    A manhole cover is a removable plate forming the lid over the opening of a manhole to allow traffic to pass over the manhole and to prevent people from falling in. Because most manhole covers are placed in roadway traffic lanes, if these manhole covers are not appropriately installed or maintained, they can represent unexpected hazards on the road, especially for motorcycle drivers. The objective of this study is to identify the effects of manhole cover characteristics as well as driver factors and traffic and roadway conditions on motorcycle driver maneuvers. A video camera was used to record motorcycle drivers' maneuvers when they encountered an inappropriately installed or maintained manhole cover. Information on 3059 drivers' maneuver decisions was recorded. Classification and regression tree (CART) models were applied to explore factors that can significantly affect motorcycle driver maneuvers when passing a manhole cover. Nearly 50 percent of the motorcycle drivers decelerated or changed their driving path to reduce the effects of the manhole cover. The manhole cover characteristics including the level difference between manhole cover and pavement, the pavement condition over the manhole cover, and the size of the manhole cover can significantly affect motorcycle driver maneuvers. Other factors, including traffic conditions, lane width, motorcycle speed, and loading conditions, also have significant effects on motorcycle driver maneuvers. To reduce the effects and potential risks from the manhole covers, highway authorities not only need to make sure that any newly installed manhole covers are as level as possible but also need to regularly maintain all the manhole covers to ensure that they are in good condition. In the long run, the size of manhole covers should be kept as small as possible so that the impact of manhole covers on motorcycle drivers can be effectively reduced. Supplemental materials are available for this article. Go to the publisher

  15. Effect of a hybrid maneuver in treating posterior canal benign paroxysmal positional vertigo.

    Badawy, Wanees M A; Gad El-Mawla, Ebtessam K; Chedid, Ahmed E F; Mustafa, Ahmed H A

    2015-02-01

    Benign paroxysmal positional vertigo (BPPV) is the most common disorder of the vestibular system of the inner ear, which is a vital part of maintaining balance. Although the efficacy of the Epley maneuver-also known as the canalith repositioning maneuver (CRM)-is well established, data comparing CRM versus a hybrid treatment are lacking. The purpose of this study was to determine the effect of a hybrid treatment, the Gans repositioning maneuver (GRM) either with or without postmaneuver restrictions, compared with CRM on treatment of posterior canal BPPV (PC-BPPV). Study design was a randomized controlled trial. A total of 45 patients (30 males and 15 females) with unilateral PC-BPPV were randomly allocated to one of three equal groups on the basis of the date of the first visit with matched assignment for gender: a GRMR group (GRM with postmaneuver restrictions), a GRM group, and a CRM group. Patients received weekly administration of the maneuver until resolution of symptoms. The Dix-Hallpike test was performed before treatment at every appointment, and finally after 1 mo from the last maneuver. Nystagmus duration and vertigo intensity were recorded. The supine roll test was performed in case the Dix-Hallpike test was negative to test otoconial migration. Data were analyzed with repeated-measures analysis of variance, paired t-tests with a Bonferroni correction, and the Spearman rank correlation coefficient. All patients showed improvement within the groups, and PC-BPPV symptoms were resolved by an average of 2, 1.7, and 1.6 maneuvers for GRMR, GRM, and CRM, respectively, with no statistical differences among the three groups (p > 0.05). Only two patients had recurrence, and one patient had horizontal BPPV at 1 mo follow-up. We demonstrated that the GRM as a new treatment is effective in treating PC-BPPV with no benefits to postmaneuver restrictions. American Academy of Audiology.

  16. Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets

    Cunbao Liu

    2017-11-01

    Full Text Available Cathelicidin-BF, derived from the banded krait (Bungarus fasciatus, is a typically cationic, amphiphilic and α-helical antimicrobial peptide (AMP with 30 amino acids that exerts powerful effects on multidrug-resistant (MDR clinical isolates, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, but whether it targets plasma membranes or intracellular targets to kill bacteria is still controversial. In the present study, we demonstrated that the disruption of bacterial membranes with high concentrations of cathelicidin-BF was the cause of bacterial death, as with conventional antibiotics at high concentrations. At lower concentrations, cathelicidin-BF did not cause bacterial plasma membrane disruption, but it was able to cross the membrane and aggregate at the nucleoid regions. Functional proteins of the transcription processes of P. aeruginosa and A. baumannii were affected by sublethal doses of cathelicidin-BF, as demonstrated by comparative proteomics using isobaric tags for relative and absolute quantification and subsequent gene ontology (GO analysis. Analysis using the Kyoto Encyclopedia of Genes and Genomes showed that cathelicidin-BF mainly interferes with metabolic pathways related to amino acid synthesis, metabolism of cofactors and vitamins, metabolism of purine and energy supply, and other processes. Although specific targets of cathelicidin-BF must still be validated, our study offers strong evidence that cathelicidin-BF may act upon intracellular targets to kill superbugs, which may be helpful for further efforts to discover novel antibiotics to fight against them.

  17. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

    Lang, Yaoguo; Xu, Shidong; Ma, Jianqun; Wu, Jun [Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Jin, Shi; Cao, Shoubo [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Yu, Yan, E-mail: yuyan@hrbmu.edu.cn [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China)

    2014-07-18

    Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

  18. The RNA Template Channel of the RNA-Dependent RNA Polymerase as a Target for Development of Antiviral Therapy of Multiple Genera within a Virus Family

    van der Linden, Lonneke; Vives-Adrián, Laia; Selisko, Barbara; Ferrer-Orta, Cristina; Liu, Xinran; Lanke, Kjerstin; Ulferts, Rachel; De Palma, Armando M; Tanchis, Federica; Goris, Nesya; Lefebvre, David; De Clercq, Kris; Leyssen, Pieter; Lacroix, Céline; Pürstinger, Gerhard; Coutard, Bruno; Canard, Bruno; Boehr, David D; Arnold, Jamie J; Cameron, Craig E; Verdaguer, Nuria; Neyts, Johan; van Kuppeveld, Frank J M

    2015-01-01

    The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy.

  19. Maneuver Acoustic Flight Test of the Bell 430 Helicopter Data Report

    Watts, Michael E.; Greenwood, Eric; Smith, Charles D.; Snider, Royce; Conner, David A.

    2014-01-01

    A cooperative ight test by NASA, Bell Helicopter and the U.S. Army to characterize the steady state acoustics and measure the maneuver noise of a Bell Helicopter 430 aircraft was accomplished. The test occurred during June/July 2011 at Eglin Air Force Base, Florida. This test gathered a total of 410 test points over 10 test days and compiled an extensive database of dynamic maneuver measurements. Three microphone arrays with up to 31 microphon. es in each were used to acquire acoustic data. Aircraft data included Differential Global Positioning System, aircraft state and rotor state information. This paper provides an overview of the test and documents the data acquired.

  20. Catheter Entrapment During Posterior Mitral Leaflet Pushing Maneuver for MitraClip Implantation.

    Castrodeza, Javier; Amat-Santos, Ignacio J; Tobar, Javier; Varela-Falcón, Luis H

    2016-06-01

    MitraClip (Abbott Vascular) therapy has been reported to be an effective procedure for mitral regurgitation, especially in high-risk patients. Recently, the novel pushing maneuver technique has been described for approaching restricted and short posterior leaflets with a pigtail catheter in order to facilitate grasping of the clip. However, complications or unexpected situations may occur. We report the case of an 84-year-old patient who underwent MitraClip implantation wherein the pushing maneuver was complicated by the clip accidentally gripping the pigtail catheter along with the two leaflets.

  1. Effects of the Eccentricity of a Perturbing Third Body on the Orbital Correction Maneuvers of a Spacecraft

    R. C. Domingos

    2014-01-01

    Full Text Available The fuel consumption required by the orbital maneuvers when correcting perturbations on the orbit of a spacecraft due to a perturbing body was estimated. The main goals are the measurement of the influence of the eccentricity of the perturbing body on the fuel consumption required by the station keeping maneuvers and the validation of the averaged methods when applied to the problem of predicting orbital maneuvers. To study the evolution of the orbits, the restricted elliptic three-body problem and the single- and double-averaged models are used. Maneuvers are made by using impulsive and low thrust maneuvers. The results indicated that the averaged models are good to make predictions for the orbital maneuvers when the spacecraft is in a high inclined orbit. The eccentricity of the perturbing body plays an important role in increasing the effects of the perturbation and the fuel consumption required for the station keeping maneuvers. It is shown that the use of more frequent maneuvers decreases the annual cost of the station keeping to correct the orbit of a spacecraft. An example of an eccentric planetary system of importance to apply the present study is the dwarf planet Haumea and its moons, one of them in an eccentric orbit.

  2. 78 FR 11555 - Special Conditions: Embraer S.A., Model EMB-550 Airplane; Design Roll Maneuver for Electronic...

    2013-02-19

    ... Law 92-574, the ``Noise Control Act of 1972.'' The FAA issues special conditions, as defined in 14 CFR...; Design Roll Maneuver for Electronic Flight Controls AGENCY: Federal Aviation Administration (FAA), DOT... design roll maneuver for electronic flight controls, specifically an electronic flight control system...

  3. 77 FR 70384 - Special Conditions: Embraer S.A., Model EMB-550 Airplane; Design Roll Maneuver for Electronic...

    2012-11-26

    ... Law 92-574, the ``Noise Control Act of 1972.'' The FAA issues special conditions, as defined in 14 CFR... Maneuver for Electronic Flight Controls AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... design roll maneuver for electronic flight controls, specifically an electronic flight control system...

  4. Pressure applied by the healthcare staff on a cricoids cartilage simulator during Sellick's maneuver in rapid sequence intubation

    J.A. Calvache (Jose Andrés); L.C.B. Sandoval (Luz); W.A. Vargas (William Andres)

    2013-01-01

    textabstractBackground: Sellick's maneuver or cricoid pressure is a strategy used to prevent bronchoaspiration during the rapid intubation sequence. Several studies have described that the force required for an adequate maneuver is of 2.5-3.5 kg. The purpose of this paper was to determine the force

  5. Optical Remote Sensing for Fence-Line Monitoring using Open-Path Quantum Cascade Laser (QCL) mono-static system for multiple target compounds in the Mid IR 7-13um (Fingerprint) region.

    Zemek, P. G.

    2017-12-01

    Quantum Cascade Lasers (QCLs) are quickly replacing Tunable Diode Lasers (TDL) for multi-target species identification and quantification in both extractive and open-path (OP) Optical Remote Sensing (ORS) fence-line instrumentation. As was seen with TDL incorporation and pricing drops as the adoption by the telecommunications industry and its current scaling has improved robustness and pricing, the QCL is also, albiet more slowly, becoming a mature market. There are several advantages of QCLs over conventional TDLs such as improved brightness and beam density, high resolution, as well as the incorporation of external etalons or internal gratings to scan over wide spectral areas. QCLs typically operate in the Mid infra-red (MIR) as opposed to the Near-Infrared (NIR) region used with TDL. The MidIR is a target rich absorption band area where compounds have high absorbtivity coefficients resulting in better detection limits as compared to TDL instruments. The use of novel chemometrics and more sensitive non-cryo-cooled detectors has allowed some of the first QCL open-path instruments in both active and passive operation. Data and field studies of one of the newest QCL OP systems is presented that allows one system to measure multiple target compounds. Multiple QCL spectral regions may be stitched together to increase the capability of QCLs over TDL OP systems. A comparison of several ORS type systems will be presented.

  6. Charged particle fusion targets

    Bangerter, R.O.; Meeker, D.J.

    1977-01-01

    The power, voltage, energy and other requirements of electron and ion beam fusion targets are reviewed. Single shell, multiple shell and magnetically insulated target designs are discussed. Questions of stability are also considered. In particular, it is shown that ion beam targets are stabilized by an energy spread in the ion beam

  7. The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.

    Lonneke van der Linden

    2015-03-01

    Full Text Available The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71 for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. Most non-nucleoside inhibitors (NNIs target surface cavities, which are structurally more flexible than the nucleotide-binding pocket, and hence have a more narrow spectrum of activity and are more prone to resistance development. Here, we report a novel NNI, GPC-N114 (2,2'-[(4-chloro-1,2-phenylenebis(oxy]bis(5-nitro-benzonitrile with broad-spectrum activity against enteroviruses and cardioviruses (another genus in the picornavirus family. Surprisingly, coxsackievirus B3 (CVB3 and poliovirus displayed a high genetic barrier to resistance against GPC-N114. By contrast, EMCV, a cardiovirus, rapidly acquired resistance due to mutations in 3Dpol. In vitro polymerase activity assays showed that GPC-N114 i inhibited the elongation activity of recombinant CVB3 and EMCV 3Dpol, (ii had reduced activity against EMCV 3Dpol with the resistance mutations, and (iii was most efficient in inhibiting 3Dpol when added before the RNA template-primer duplex. Elucidation of a crystal structure of the inhibitor bound to CVB3 3Dpol confirmed the RNA-binding channel as the target for GPC-N114. Docking studies of the compound into the crystal structures of the compound-resistant EMCV 3Dpol mutants suggested that the resistant phenotype is due to subtle changes that interfere with the binding of GPC-N114 but not of the RNA template-primer. In conclusion, this study presents the first NNI that targets the RNA template channel of the picornavirus polymerase and identifies a new pocket that can be used for the design of broad-spectrum inhibitors. Moreover, this study provides important new insight

  8. High- and Low-Order Overtaking-Ability Affordances: Drivers Rely on the Maximum Velocity and Acceleration of Their Cars to Perform Overtaking Maneuvers.

    Basilio, Numa; Morice, Antoine H P; Marti, Geoffrey; Montagne, Gilles

    2015-08-01

    The aim of this study was to answer the question, Do drivers take into account the action boundaries of their car when overtaking? The Morice et al. affordance-based approach to visually guided overtaking suggests that the "overtake-ability" affordance can be formalized as the ratio of the "minimum satisfying velocity" (MSV) of the maneuver to the maximum velocity (V(max)) of the driven car. In this definition, however, the maximum acceleration (A(max)) of the vehicle is ignored. We hypothesize that drivers may be sensitive to an affordance redefined with the ratio of the "minimum satisfying acceleration" (MSA) to the A(max) of the car. Two groups of nine drivers drove cars differing in their A(max). They were instructed to attempt overtaking maneuvers in 25 situations resulting from the combination of five MSA and five MSV values. When overtaking frequency was expressed as a function of MSV and MSA, maneuvers were found to be initiated differently for the two groups. However, when expressed as a function of MSV/V(max) and MSA/A(max), overtaking frequency was quite similar for both groups. Finally, a multiple regression coefficient analysis demonstrated that overtaking decisions are fully explained by a composite variable comprising MSA/A(max) and the time required to reach MSV. Drivers reliably decide whether overtaking is safe (or not) by using low- and high-order variables taking into account their car's maximum velocity and acceleration, respectively, as predicted by "affordance-based control" theory. Potential applications include the design of overtaking assistance, which should exploit the MSA/A(max) variables in order to suggest perceptually relevant overtaking solutions. © 2015, Human Factors and Ergonomics Society.

  9. Huang's three-step maneuver shortens the learning curve of laparoscopic spleen-preserving splenic hilar lymphadenectomy.

    Huang, Chang-Ming; Huang, Ze-Ning; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Jun, Lu; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Tu, Ru-Hong

    2017-12-01

    The goal of this study was to investigate the difference between the learning curves of different maneuvers in laparoscopic spleen-preserving splenic hilar lymphadenectomy for advanced upper gastric cancer. From January 2010 to April 2014, 53 consecutive patients who underwent laparoscopic spleen-preserving splenic hilar lymphadenectomy via the traditional-step maneuver (group A) and 53 consecutive patients via Huang's three-step maneuver (group B) were retrospectively analyzed. No significant difference in patient characteristics were found between the two groups. The learning curves of groups A and B were divided into phase 1 (1-43 cases and 1-30 cases, respectively) and phase 2 (44-53 cases and 31-53 cases, respectively). Compared with group A, the dissection time, bleeding loss and vascular injury were significantly decreased in group B. No significant differences in short-term outcomes were found between the two maneuvers. The multivariate analysis indicated that the body mass index, short gastric vessels, splenic artery type and maneuver were significantly associated with the dissection time in group B. No significant difference in the survival curve was found between the maneuvers. The learning curve of Huang's three-step maneuver was shorter than that of the traditional-step maneuver, and the former represents an ideal maneuver for laparoscopic spleen-preserving splenic hilar lymphadenectomy.To shorten the learning curve at the beginning of laparoscopic spleen-preserving splenic hilar lymphadenectomy, beginners should beneficially use Huang's three-step maneuver and select patients with advanced upper gastric cancer with a body mass index of less than 25 kg/m 2 and the concentrated type of splenic artery. Copyright © 2017. Published by Elsevier Ltd.

  10. Nanosatellite Maneuver Planning for Point Cloud Generation With a Rangefinder

    2015-06-05

    may drive large eccentricity changes or pull the chaser too far away from its target. Limitations on waypoint selection are considered below. B...the local horizontal (RAAN ∼0◦) will have high relative orbit eccentricities and consequently result in increased propellant consumption. The...obtain an edge metric score below 0.3. Coverage time is capped at 36 h. It is assumed that the chaser employs reaction wheels as the actuators of the

  11. Analysis of risk factors influencing the outcome of the Epley maneuver.

    Domínguez-Durán, E; Domènech-Vadillo, E; Álvarez-Morujo de Sande, M G; González-Aguado, R; Guerra-Jiménez, G; Ramos-Macías, Á; Morales-Angulo, C; Martín-Mateos, A J; Figuerola-Massana, E; Galera-Ruiz, H

    2017-10-01

    Benign paroxysmal positional vertigo (BPPV) is the most frequent type of vertigo. The treatment of canalithiasis of the posterior semicircular canal consists in performing a particle-repositioning maneuver, such as the Epley maneuver (EM). However, the EM is not effective in all cases. The objective of this study is to identify risk factors, which predict the EM failure, among the clinical variables recorded in anamnesis and patient examination. This is an observational prospective multicentric study. All patients presenting with BPPV were recruited and applied the EM and appointed for a follow-up visit 7 days later. The following variables were recorded: sex, age, arterial hypertension, diabetes, hyperlipidemia, smoking habit, alcohol consumption, migraine, osteoporosis, diseases of the inner ear, previous ipsilateral BPPV, previous traumatic brain injury, previous sudden head deceleration, time of evolution, sulpiride or betahistine treatment, experienced symptoms, outcome of the Halmagyi maneuver, laterality, cephalic hyperextension of the neck, intensity of nystagmus, intensity of vertigo, duration of nystagmus, occurrence of orthotropic nystagmus, symptoms immediately after the EM, postural restrictions, and symptoms 7 days after the EM. Significant differences in the rate of loss of nystagmus were found for six variables: hyperlipidemia, previous ipsilateral BPPV, intensity of nystagmus, duration of nystagmus, post-maneuver sweating, and subjective status. The most useful significant variables in the clinical practice to predict the success of the EM are previous BPPV and intensity of nystagmus. In the other significant variables, no physiopathological hypothesis can be formulated or differences between groups are too small.

  12. Multislice spiral computed tomography to determine the effects of a recruitment maneuver in experimental lung injury

    Henzler, Dietrich; Rossaint, Rolf [University Hospital, RWTH Aachen, Anesthesiology Department, Aachen (Germany); Mahnken, Andreas H.; Wildberger, Joachim E.; Guenther, Rolf W. [University Hospital of the RWTH Aachen, Clinic of Diagnostic Radiology, Aachen (Germany); Kuhlen, Ralf [University Hospital of the RWTH Aachen, Operative Intensive Care Department, Aachen (Germany)

    2006-06-15

    Although recruitment of atelectatic lung is a common aim in acute respiratory distress syndrome (ARDS), the effects of a recruitment maneuver have not been assessed quantitatively. By multislice spiral CT (MSCT), we analyzed the changes in lung volumes calculated from the changes in the CT values of hyperinflated (V{sub HYP}), normally (V{sub NORM}), poorly (V{sub POOR}) and nonaerated (V{sub NON}) lung in eight mechanically ventilated pigs with saline lavage-induced acute lung injury before and after a recruitment maneuver. This was compared to single slice analysis near the diaphragm. The increase in aerated lung was mainly for V{sub POOR} and the less in V{sub NORM}. Total lung volume and intrathoracic gas increased. No differences were found for tidal volumes measured by spirometry or determined by CT. The inspiratory-expiratory volume differences were not different after the recruitment maneuver in V{sub NON} (from 62{+-}18 ml to 43{+-}26 ml, P=0.114), and in V{sub NORM} (from 216{+-}51 ml to 251{+-}37 ml, P=0.102). Single slice analysis significantly underestimated the increase in normally and poorly aerated lung. Quantitative analysis of lung volumes by whole lung MSCT revealed the increase of poorly aerated lung as the main mechanism of a standard recruitment maneuver. MSCT can provide additional information as compared to single slice CT. (orig.)

  13. Cooperative maneuvering in close environments among cybercars and dual-mode cars

    Milanés, V.; Alonso, J.; Bouraoui, L.; Ploeg, J.

    2011-01-01

    This paper describes the results of vehicle-to-vehicle (V2V) and infrastructure-to-vehicle (I2V) experiments implementing cooperative maneuvering for three different vehicles driving automatically. The cars used were cybercars from the Institut National de Recherche en Informatique et Automatique

  14. The Prospect of Responsive Spacecraft Using Aeroassisted, Trans-Atmospheric Maneuvers

    2014-06-19

    99 V. Design of Experiments Approach to Atmospheric Skip Entry Maneuver Optimization .....100 Chapter Overview...Transfer Diagram .................................................................................................11 3.1. Comparison of Geocentric ...Comparison of Geocentric /Geodetic Latitude for Apollo 10 (2-Gravity Model, Fourth-Order Runge-Kutta Solver

  15. Conflict Resolution Performance in an Experimental Study of En Route Free Maneuvering Operations

    Doble, Nathan A.; Barhydt, Richard; Hitt, James M., II

    2005-01-01

    NASA has developed a far-term air traffic management concept, termed Distributed Air/Ground Traffic Management (DAG-TM). One component of DAG-TM, En Route Free Maneuvering, allows properly trained flight crews of equipped autonomous aircraft to assume responsibility for separation from other autonomous aircraft and from Instrument Flight Rules (IFR) aircraft. Ground-based air traffic controllers continue to separate IFR traffic and issue flow management constraints to all aircraft. To examine En Route Free Maneuvering operations, a joint human-in-the-loop experiment was conducted in summer 2004 at the NASA Ames and Langley Research Centers. Test subject pilots used desktop flight simulators to resolve traffic conflicts and adhere to air traffic flow constraints issued by subject controllers. The experimental airspace integrated both autonomous and IFR aircraft at varying traffic densities. This paper presents a subset of the En Route Free Maneuvering experimental results, focusing on airborne and ground-based conflict resolution, and the effects of increased traffic levels on the ability of pilots and air traffic controllers to perform this task. The results show that, in general, increases in autonomous traffic do not significantly impact conflict resolution performance. In addition, pilot acceptability of autonomous operations remains high throughout the range of traffic densities studied. Together with previously reported findings, these results continue to support the feasibility of the En Route Free Maneuvering component of DAG-TM.

  16. 46 CFR 35.20-40 - Maneuvering characteristics-T/OC.

    2010-10-01

    ... for the normal load and normal ballast condition for: (1) Calm weather—wind 10 knots or less, calm sea... response of the (name of the vessel) may be different from those listed above if any of the following conditions, upon which the maneuvering information is based, are varied: (1) Calm weather—wind 10 knots or...

  17. Linearity of electrical impedance tomography during maximum effort breathing and forced expiration maneuvers.

    Ngo, Chuong; Leonhardt, Steffen; Zhang, Tony; Lüken, Markus; Misgeld, Berno; Vollmer, Thomas; Tenbrock, Klaus; Lehmann, Sylvia

    2017-01-01

    Electrical impedance tomography (EIT) provides global and regional information about ventilation by means of relative changes in electrical impedance measured with electrodes placed around the thorax. In combination with lung function tests, e.g. spirometry and body plethysmography, regional information about lung ventilation can be achieved. Impedance changes strictly correlate with lung volume during tidal breathing and mechanical ventilation. Initial studies presumed a correlation also during forced expiration maneuvers. To quantify the validity of this correlation in extreme lung volume changes during forced breathing, a measurement system was set up and applied on seven lung-healthy volunteers. Simultaneous measurements of changes in lung volume using EIT imaging and pneumotachography were obtained with different breathing patterns. Data was divided into a synchronizing phase (spontaneous breathing) and a test phase (maximum effort breathing and forced maneuvers). The EIT impedance changes correlate strictly with spirometric data during slow breathing with increasing and maximum effort ([Formula: see text]) and during forced expiration maneuvers ([Formula: see text]). Strong correlations in spirometric volume parameters [Formula: see text] ([Formula: see text]), [Formula: see text]/FVC ([Formula: see text]), and flow parameters PEF, [Formula: see text], [Formula: see text], [Formula: see text] ([Formula: see text]) were observed. According to the linearity during forced expiration maneuvers, EIT can be used during pulmonary function testing in combination with spirometry for visualisation of regional lung ventilation.

  18. Multislice spiral computed tomography to determine the effects of a recruitment maneuver in experimental lung injury

    Henzler, Dietrich; Rossaint, Rolf; Mahnken, Andreas H.; Wildberger, Joachim E.; Guenther, Rolf W.; Kuhlen, Ralf

    2006-01-01

    Although recruitment of atelectatic lung is a common aim in acute respiratory distress syndrome (ARDS), the effects of a recruitment maneuver have not been assessed quantitatively. By multislice spiral CT (MSCT), we analyzed the changes in lung volumes calculated from the changes in the CT values of hyperinflated (V HYP ), normally (V NORM ), poorly (V POOR ) and nonaerated (V NON ) lung in eight mechanically ventilated pigs with saline lavage-induced acute lung injury before and after a recruitment maneuver. This was compared to single slice analysis near the diaphragm. The increase in aerated lung was mainly for V POOR and the less in V NORM . Total lung volume and intrathoracic gas increased. No differences were found for tidal volumes measured by spirometry or determined by CT. The inspiratory-expiratory volume differences were not different after the recruitment maneuver in V NON (from 62±18 ml to 43±26 ml, P=0.114), and in V NORM (from 216±51 ml to 251±37 ml, P=0.102). Single slice analysis significantly underestimated the increase in normally and poorly aerated lung. Quantitative analysis of lung volumes by whole lung MSCT revealed the increase of poorly aerated lung as the main mechanism of a standard recruitment maneuver. MSCT can provide additional information as compared to single slice CT. (orig.)

  19. Associating Crash Avoidance Maneuvers with Driver Attributes and Accident Characteristics: A Mixed Logit Model Approach

    Kaplan, Sigal; Prato, Carlo Giacomo

    2012-01-01

    as from the key role of the ability of drivers to perform effective corrective maneuvers for the success of automated in-vehicle warning and driver assistance systems. The analysis is conducted by means of a mixed logit model that accommodates correlations across alternatives and heteroscedasticity. Data...

  20. Leveraging Manet and Mobile Devices in Ship-to-Objective Maneuver and Expeditionary MAGTF Operations

    2014-09-01

    support and firepower. ECO allows for the Marine Corps to deploy a lower- level maneuver unit as an economy of force measure to assert combat power over...to the Global Information Grid ( GIG ) is the course of action the Marine Corps should adopt (Price & McHuen, 2009). My proposed research addresses