WorldWideScience

Sample records for small targets moving

  1. Infrared Small Moving Target Detection via Saliency Histogram and Geometrical Invariability

    Directory of Open Access Journals (Sweden)

    Minjie Wan

    2017-06-01

    Full Text Available In order to detect both bright and dark small moving targets effectively in infrared (IR video sequences, a saliency histogram and geometrical invariability based method is presented in this paper. First, a saliency map that roughly highlights the salient regions of the original image is obtained by tuning its amplitude spectrum in the frequency domain. Then, a saliency histogram is constructed by means of averaging the accumulated saliency value of each gray level in the map, through which bins corresponding to bright target and dark target are assigned with large values in the histogram. Next, single-frame detection of candidate targets is accomplished by a binarized segmentation using an adaptive threshold, and their centroid coordinates with sub-pixel accuracy are calculated through a connected components labeling method as well as a gray-weighted criterion. Finally, considering the motion characteristics in consecutive frames, an inter-frame false alarm suppression method based on geometrical invariability is developed to improve the precision rate further. Quantitative analyses demonstrate the detecting precision of this proposed approach can be up to 97% and Receiver Operating Characteristic (ROC curves further verify our method outperforms other state-of-the-arts methods in both detection rate and false alarm rate.

  2. Heterogeneous CPU-GPU moving targets detection for UAV video

    Science.gov (United States)

    Li, Maowen; Tang, Linbo; Han, Yuqi; Yu, Chunlei; Zhang, Chao; Fu, Huiquan

    2017-07-01

    Moving targets detection is gaining popularity in civilian and military applications. On some monitoring platform of motion detection, some low-resolution stationary cameras are replaced by moving HD camera based on UAVs. The pixels of moving targets in the HD Video taken by UAV are always in a minority, and the background of the frame is usually moving because of the motion of UAVs. The high computational cost of the algorithm prevents running it at higher resolutions the pixels of frame. Hence, to solve the problem of moving targets detection based UAVs video, we propose a heterogeneous CPU-GPU moving target detection algorithm for UAV video. More specifically, we use background registration to eliminate the impact of the moving background and frame difference to detect small moving targets. In order to achieve the effect of real-time processing, we design the solution of heterogeneous CPU-GPU framework for our method. The experimental results show that our method can detect the main moving targets from the HD video taken by UAV, and the average process time is 52.16ms per frame which is fast enough to solve the problem.

  3. Moving Target Photometry Using WISE and NEOWISE

    Science.gov (United States)

    Wright, Edward L.

    2015-01-01

    WISE band 1 observations have a significant noise contribution from confusion. The image subtraction done on W0855-0714 by Wright et al. (2014) shows that this noise source can be eliminated for sources that move by much more than the beamsize. This paper describes an analysis that includes a pattern of celestially fixed flux plus a source moving with a known trajectory. This technique allows the confusion noise to be modeled with nuisance parameters and removed even for sources that have not moved by many beamwidths. However, the detector noise is magnified if the motion is too small. Examples of the method applied to fast moving Y dwarfs and slow moving planets will be shown.

  4. Camouflage, detection and identification of moving targets.

    Science.gov (United States)

    Hall, Joanna R; Cuthill, Innes C; Baddeley, Roland; Shohet, Adam J; Scott-Samuel, Nicholas E

    2013-05-07

    Nearly all research on camouflage has investigated its effectiveness for concealing stationary objects. However, animals have to move, and patterns that only work when the subject is static will heavily constrain behaviour. We investigated the effects of different camouflages on the three stages of predation-detection, identification and capture-in a computer-based task with humans. An initial experiment tested seven camouflage strategies on static stimuli. In line with previous literature, background-matching and disruptive patterns were found to be most successful. Experiment 2 showed that if stimuli move, an isolated moving object on a stationary background cannot avoid detection or capture regardless of the type of camouflage. Experiment 3 used an identification task and showed that while camouflage is unable to slow detection or capture, camouflaged targets are harder to identify than uncamouflaged targets when similar background objects are present. The specific details of the camouflage patterns have little impact on this effect. If one has to move, camouflage cannot impede detection; but if one is surrounded by similar targets (e.g. other animals in a herd, or moving background distractors), then camouflage can slow identification. Despite previous assumptions, motion does not entirely 'break' camouflage.

  5. Cooperative Robots to Observe Moving Targets: Review.

    Science.gov (United States)

    Khan, Asif; Rinner, Bernhard; Cavallaro, Andrea

    2018-01-01

    The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time. We classify and critically discuss the control techniques: cooperative multirobot observation of multiple moving targets, cooperative search, acquisition, and track, cooperative tracking, and multirobot pursuit evasion. We also identify the five major elements that characterize this problem, namely, the coordination method, the environment, the target, the robot and its sensor(s). These elements are used to systematically analyze the control techniques. The majority of the studied work is based on simulation and laboratory studies, which may not accurately reflect real-world operational conditions. Importantly, while our systematic analysis is focused on multitarget observation, our proposed classification is useful also for related multirobot applications.

  6. Computing proton dose to irregularly moving targets

    International Nuclear Information System (INIS)

    Phillips, Justin; Gueorguiev, Gueorgui; Grassberger, Clemens; Dowdell, Stephen; Paganetti, Harald; Sharp, Gregory C; Shackleford, James A

    2014-01-01

    Purpose: While four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery. Methods: The procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion. Results: A passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, 95.7% with 3 cm drift in

  7. Minefield overwatch using moving target indicator radar

    Science.gov (United States)

    Donadio, Anthony; Ewing, Robert; Kenneally, William J.; Santapietro, John J.

    1999-07-01

    Traditional antipersonnel land mines are an effective military tool, but they are unable to distinguish friend from foe, or civilian from military personnel. The concept described here uses an advanced moving target indicator (MTI) radar to scan the minefield in order to detect movement towards or within the minefield, coupled with visual identification by a human operator and a communication link for command and control. Selected mines in the minefield can then be activated by means of the command link. In order to demonstrate this concept, a 3D, interactive simulation has been developed. This simulation builds on previous work by integrating a detailed analytical model of an MTI radar. This model has been tailored to the specific application of detection of slowly moving dismounted entities immersed in ground clutter. The model incorporates the effects of internal scatterer motion and antenna scanning modulation in order to provide a realistic representation of the detection problem in this environment. The angle information on the MTI target detection is then passed to a virtual 3D sight which cues a human operator to the target location. In addition, radar propagation effects and an experimental design in which the radar itself is used as a command link are explored.

  8. A ground moving target emergency tracking method for catastrophe rescue

    Science.gov (United States)

    Zhou, X.; Li, D.; Li, G.

    2014-11-01

    In recent years, great disasters happen now and then. Disaster management test the emergency operation ability of the government and society all over the world. Immediately after the occurrence of a great disaster (e.g., earthquake), a massive nationwide rescue and relief operation need to be kicked off instantly. In order to improve the organizations efficiency of the emergency rescue, the organizers need to take charge of the information of the rescuer teams, including the real time location, the equipment with the team, the technical skills of the rescuers, and so on. One of the key factors for the success of emergency operations is the real time location of the rescuers dynamically. Real time tracking methods are used to track the professional rescuer teams now. But volunteers' participation play more and more important roles in great disasters. However, real time tracking of the volunteers will cause many problems, e.g., privacy leakage, expensive data consumption, etc. These problems may reduce the enthusiasm of volunteers' participation for catastrophe rescue. In fact, the great disaster is just small probability event, it is not necessary to track the volunteers (even rescuer teams) every time every day. In order to solve this problem, a ground moving target emergency tracking method for catastrophe rescue is presented in this paper. In this method, the handheld devices using GPS technology to provide the location of the users, e.g., smart phone, is used as the positioning equipment; an emergency tracking information database including the ID of the ground moving target (including the rescuer teams and volunteers), the communication number of the handheld devices with the moving target, and the usually living region, etc., is built in advance by registration; when catastrophe happens, the ground moving targets that living close to the disaster area will be filtered by the usually living region; then the activation short message will be sent to the selected

  9. Evaluating Moving Target Defense with PLADD

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Stephen T. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Outkin, Alexander V. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Gearhart, Jared Lee [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Hobbs, Jacob Aaron [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Siirola, John Daniel [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Phillips, Cynthia A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Verzi, Stephen Joseph [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Tauritz, Daniel [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Mulder, Samuel A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Naugle, Asmeret Bier [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-09-15

    This project evaluates the effectiveness of moving target defense (MTD) techniques using a new game we have designed, called PLADD, inspired by the game FlipIt [28]. PLADD extends FlipIt by incorporating what we believe are key MTD concepts. We have analyzed PLADD and proven the existence of a defender strategy that pushes a rational attacker out of the game, demonstrated how limited the strategies available to an attacker are in PLADD, and derived analytic expressions for the expected utility of the game’s players in multiple game variants. We have created an algorithm for finding a defender’s optimal PLADD strategy. We show that in the special case of achieving deterrence in PLADD, MTD is not always cost effective and that its optimal deployment may shift abruptly from not using MTD at all to using it as aggressively as possible. We believe our effort provides basic, fundamental insights into the use of MTD, but conclude that a truly practical analysis requires model selection and calibration based on real scenarios and empirical data. We propose several avenues for further inquiry, including (1) agents with adaptive capabilities more reflective of real world adversaries, (2) the presence of multiple, heterogeneous adversaries, (3) computational game theory-based approaches such as coevolution to allow scaling to the real world beyond the limitations of analytical analysis and classical game theory, (4) mapping the game to real-world scenarios, (5) taking player risk into account when designing a strategy (in addition to expected payoff), (6) improving our understanding of the dynamic nature of MTD-inspired games by using a martingale representation, defensive forecasting, and techniques from signal processing, and (7) using adversarial games to develop inherently resilient cyber systems.

  10. Small UAS Analysis of Laser Designation and Search and Target Acquisition Capabilities in an Urban Environment

    National Research Council Canada - National Science Library

    Harclerode, Eric

    2008-01-01

    Conclusions: -Small UAS has extreme difficulty lasing moving targets in high density urban environments -Lasing moving targets in medium density terrain is possible but not certain -Lasing of stationary targets...

  11. Error Analysis of Fast Moving Target Geo-location in Wide Area Surveillance Ground Moving Target Indication Mode

    Directory of Open Access Journals (Sweden)

    Zheng Shi-chao

    2013-12-01

    Full Text Available As an important mode in airborne radar systems, Wide Area Surveillance Ground Moving Target Indication (WAS-GMTI mode has the ability of monitoring a large area in a short time, and then the detected moving targets can be located quickly. However, in real environment, many factors introduce considerable errors into the location of moving targets. In this paper, a fast location method based on the characteristics of the moving targets in WAS-GMTI mode is utilized. And in order to improve the location performance, those factors that introduce location errors are analyzed and moving targets are relocated. Finally, the analysis of those factors is proved to be reasonable by simulation and real data experiments.

  12. Detection of Moving Targets Using Soliton Resonance Effect

    Science.gov (United States)

    Kulikov, Igor K.; Zak, Michail

    2013-01-01

    The objective of this research was to develop a fundamentally new method for detecting hidden moving targets within noisy and cluttered data-streams using a novel "soliton resonance" effect in nonlinear dynamical systems. The technique uses an inhomogeneous Korteweg de Vries (KdV) equation containing moving-target information. Solution of the KdV equation will describe a soliton propagating with the same kinematic characteristics as the target. The approach uses the time-dependent data stream obtained with a sensor in form of the "forcing function," which is incorporated in an inhomogeneous KdV equation. When a hidden moving target (which in many ways resembles a soliton) encounters the natural "probe" soliton solution of the KdV equation, a strong resonance phenomenon results that makes the location and motion of the target apparent. Soliton resonance method will amplify the moving target signal, suppressing the noise. The method will be a very effective tool for locating and identifying diverse, highly dynamic targets with ill-defined characteristics in a noisy environment. The soliton resonance method for the detection of moving targets was developed in one and two dimensions. Computer simulations proved that the method could be used for detection of singe point-like targets moving with constant velocities and accelerations in 1D and along straight lines or curved trajectories in 2D. The method also allows estimation of the kinematic characteristics of moving targets, and reconstruction of target trajectories in 2D. The method could be very effective for target detection in the presence of clutter and for the case of target obscurations.

  13. Space moving target detection using time domain feature

    Science.gov (United States)

    Wang, Min; Chen, Jin-yong; Gao, Feng; Zhao, Jin-yu

    2018-01-01

    The traditional space target detection methods mainly use the spatial characteristics of the star map to detect the targets, which can not make full use of the time domain information. This paper presents a new space moving target detection method based on time domain features. We firstly construct the time spectral data of star map, then analyze the time domain features of the main objects (target, stars and the background) in star maps, finally detect the moving targets using single pulse feature of the time domain signal. The real star map target detection experimental results show that the proposed method can effectively detect the trajectory of moving targets in the star map sequence, and the detection probability achieves 99% when the false alarm rate is about 8×10-5, which outperforms those of compared algorithms.

  14. Artifacts in Radar Imaging of Moving Targets

    Science.gov (United States)

    2012-09-01

    CA, USA, 2007. [11] B. Borden, Radar imaging of airborne targets: A primer for Applied mathematicians and Physicists . New York, NY: Taylor and... Project (0704–0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE 21 September 2012 3. REPORT TYPE AND DATES COVERED...CW Continuous Wave DAC Digital to Analog Convertor DFT Discrete Fourier Transform FBP Filtered Back Projection FFT Fast Fourier Transform GPS

  15. Realism and Effectiveness of Robotic Moving Targets

    Science.gov (United States)

    2017-04-01

    avoid small obstacles. This variation may make the RHTTs more difficult to hit, though it can be argued that this variation (and difficulty) is more...training time. 17% Appearance Variation in appearance (size, features, etc.)/more human-like. 9% Nothing Nothing was disliked about the...J., Witmer, B. G., Goldberg , S. L., Parsons, K. J., & Parsons, J. (1998). Virtual environments for dismounted Soldier training and performance

  16. Moving targets. Economic competitiveness of nuclear power

    International Nuclear Information System (INIS)

    Rogner, H.H.; Langlois, L.

    2000-01-01

    Most world electricity markets are now moving towards greater competition, driven in part by technology, low fuel prices, and experience that competitive markets are more self-sustaining. Electric power is being sold in a number of markets in member countries of the Organization for Economic Cooperation and Development (OECD) for around US $0.02 per kilowatt-hour (kWh). Can nuclear generation match such prices? If not, can it be made to do so? Electricity companies are now in the business of selling a commodity (kWh) and commercial services instead of a strategic good. Excess capacity, low demand growth and lower product prices in major industrialized countries have forced power generators and their suppliers to be more concerned with the costs of their operations and profitability of their investments. These companies increasingly need a commercial, profit-oriented approach if they are to survive and prosper. Even more, they will need to make substantial cost reductions over the next few years. The nuclear industry is no exception. How does nuclear power stack up in this environment? The IAEA Planning and Economic Studies Section is doing a series of studies on precisely these questions, divided into issues affecting the near, medium and long-term future of nuclear power. This corresponds roughly to matters affecting existing plants, upgrades and life extensions, or new plants. In general, the studies find that nuclear power has the potential to be competitive in all three markets. But realizing that potential will require significant changes on the part of the industry and its regulators. This article focuses on the prevailing market situation in many industrialized countries. Several lessons also are applicable to developing countries, particularly in cases where the financing of electric power projects is expected to come from international capital markets. The overall situation is distinctly different for developing countries. Typically the capacity there for

  17. Quality of clinical trials: A moving target

    Science.gov (United States)

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  18. Quality of clinical trials: A moving target

    Directory of Open Access Journals (Sweden)

    Arun Bhatt

    2011-01-01

    Full Text Available Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.

  19. Spatial Release from Masking with a Moving Target

    Directory of Open Access Journals (Sweden)

    M. Torben Pastore

    2017-12-01

    Full Text Available In the visual domain, a stationary object that is difficult to detect usually becomes far more salient if it moves while the objects around it do not. This “pop out” effect is important for parsing the visual world into figure/ground relationships that allow creatures to detect food, threats, etc. We tested for an auditory correlate to this visual effect by asking listeners to identify a single word, spoken by a female, embedded with two or four masking words spoken by males. Percentage correct scores were analyzed and compared between conditions where target and maskers were presented from the same position vs. when the target was presented from one position while maskers were presented from different positions. In some trials, the target word was moved across the speaker array using amplitude panning, while in other trials that target was played from a single, static position. Results showed a spatial release from masking for all conditions where the target and maskers were not located at the same position, but there was no statistically significant difference between identification performance when the target was moving vs. when it was stationary. These results suggest that, at least for short stimulus durations (0.75 s for the stimuli in this experiment, there is unlikely to be a “pop out” effect for moving target stimuli in the auditory domain as there is in the visual domain.

  20. Moving Target Detection and Active Tracking with a Multicamera Network

    Directory of Open Access Journals (Sweden)

    Long Zhao

    2014-01-01

    Full Text Available We propose a systematic framework for Intelligence Video Surveillance System (IVSS with a multicamera network. The proposed framework consists of low-cost static and PTZ cameras, target detection and tracking algorithms, and a low-cost PTZ camera feedback control algorithm based on target information. The target detection and tracking is realized by fixed cameras using a moving target detection and tracking algorithm; the PTZ camera is manoeuvred to actively track the target from the tracking results of the static camera. The experiments are carried out using practical surveillance system data, and the experimental results show that the systematic framework and algorithms presented in this paper are efficient.

  1. Moving Target Techniques: Cyber Resilience throught Randomization, Diversity, and Dynamism

    Science.gov (United States)

    2017-03-03

    attacks. Simply put, these techniques turn systems into moving targets that will be hard for cyber attackers to compromise. MT techniques leverage...been diversified, they can attack it as if it was not diversified at all. Dynamic Data: Techniques in the dynamic data domain change the format

  2. Eye tracking a self-moved target with complex hand-target dynamics

    Science.gov (United States)

    Landelle, Caroline; Montagnini, Anna; Madelain, Laurent

    2016-01-01

    Previous work has shown that the ability to track with the eye a moving target is substantially improved when the target is self-moved by the subject's hand compared with when being externally moved. Here, we explored a situation in which the mapping between hand movement and target motion was perturbed by simulating an elastic relationship between the hand and target. Our objective was to determine whether the predictive mechanisms driving eye-hand coordination could be updated to accommodate this complex hand-target dynamics. To fully appreciate the behavioral effects of this perturbation, we compared eye tracking performance when self-moving a target with a rigid mapping (simple) and a spring mapping as well as when the subject tracked target trajectories that he/she had previously generated when using the rigid or spring mapping. Concerning the rigid mapping, our results confirmed that smooth pursuit was more accurate when the target was self-moved than externally moved. In contrast, with the spring mapping, eye tracking had initially similar low spatial accuracy (though shorter temporal lag) in the self versus externally moved conditions. However, within ∼5 min of practice, smooth pursuit improved in the self-moved spring condition, up to a level similar to the self-moved rigid condition. Subsequently, when the mapping unexpectedly switched from spring to rigid, the eye initially followed the expected target trajectory and not the real one, thereby suggesting that subjects used an internal representation of the new hand-target dynamics. Overall, these results emphasize the stunning adaptability of smooth pursuit when self-maneuvering objects with complex dynamics. PMID:27466129

  3. Moving target tracking through distributed clustering in directional sensor networks.

    Science.gov (United States)

    Enayet, Asma; Razzaque, Md Abdur; Hassan, Mohammad Mehedi; Almogren, Ahmad; Alamri, Atif

    2014-12-18

    The problem of moving target tracking in directional sensor networks (DSNs) introduces new research challenges, including optimal selection of sensing and communication sectors of the directional sensor nodes, determination of the precise location of the target and an energy-efficient data collection mechanism. Existing solutions allow individual sensor nodes to detect the target's location through collaboration among neighboring nodes, where most of the sensors are activated and communicate with the sink. Therefore, they incur much overhead, loss of energy and reduced target tracking accuracy. In this paper, we have proposed a clustering algorithm, where distributed cluster heads coordinate their member nodes in optimizing the active sensing and communication directions of the nodes, precisely determining the target location by aggregating reported sensing data from multiple nodes and transferring the resultant location information to the sink. Thus, the proposed target tracking mechanism minimizes the sensing redundancy and maximizes the number of sleeping nodes in the network. We have also investigated the dynamic approach of activating sleeping nodes on-demand so that the moving target tracking accuracy can be enhanced while maximizing the network lifetime. We have carried out our extensive simulations in ns-3, and the results show that the proposed mechanism achieves higher performance compared to the state-of-the-art works.

  4. Moving Target Detection With Compact Laser Doppler Radar

    Science.gov (United States)

    Sepp, G.; Breining, A.; Eisfeld, W.; Knopp, R.; Lill, E.; Wagner, D.

    1989-12-01

    This paper describes an experimental integrated optronic system for detection and tracking of moving objects. The system is based on a CO2 waveguide laser Doppler ra-dar with homodyne receiver and galvanometer mirror beam scanner. A "hot spot" seeker consisting of a thermal imager with image processor transmits the coordinates of IR-emitting, i.e. potentially powered, objects to the laser radar scanner. The scanner addresses these "hot" locations operating in a large field-of-view (FOV) random ac-cess mode. Hot spots exhibiting a Doppler shifted laser signal are indicated in the thermal image by velocity-to-colour encoded markers. After switching to a small FOV scanning mode, the laser Doppler radar is used to track fast moving objects. Labora-tory and field experiments with moving objects including rotating discs, automobiles and missiles are described.

  5. Moving Target Tracking through Distributed Clustering in Directional Sensor Networks

    Directory of Open Access Journals (Sweden)

    Asma Enayet

    2014-12-01

    Full Text Available The problem of moving target tracking in directional sensor networks (DSNs introduces new research challenges, including optimal selection of sensing and communication sectors of the directional sensor nodes, determination of the precise location of the target and an energy-efficient data collection mechanism. Existing solutions allow individual sensor nodes to detect the target’s location through collaboration among neighboring nodes, where most of the sensors are activated and communicate with the sink. Therefore, they incur much overhead, loss of energy and reduced target tracking accuracy. In this paper, we have proposed a clustering algorithm, where distributed cluster heads coordinate their member nodes in optimizing the active sensing and communication directions of the nodes, precisely determining the target location by aggregating reported sensing data from multiple nodes and transferring the resultant location information to the sink. Thus, the proposed target tracking mechanism minimizes the sensing redundancy and maximizes the number of sleeping nodes in the network. We have also investigated the dynamic approach of activating sleeping nodes on-demand so that the moving target tracking accuracy can be enhanced while maximizing the network lifetime. We have carried out our extensive simulations in ns-3, and the results show that the proposed mechanism achieves higher performance compared to the state-of-the-art works.

  6. Research on moving target defense based on SDN

    Science.gov (United States)

    Chen, Mingyong; Wu, Weimin

    2017-08-01

    An address mutation strategy was proposed. This strategy provided an unpredictable change in address, replacing the real address of the packet forwarding process and path mutation, thus hiding the real address of the host and path. a mobile object defense technology based on Spatio-temporal Mutation on this basis is proposed, Using the software Defined Network centralized control architecture advantage combines sFlow traffic monitoring technology and Moving Target Defense. A mutated time period which can be changed in real time according to the network traffic is changed, and the destination address is changed while the controller abruptly changes the address while the data packet is transferred between the switches to construct a moving target, confusing the host within the network, thereby protecting the host and network.

  7. Neuromorphic Modeling of Moving Target Detection in Insects

    Science.gov (United States)

    2007-12-31

    Standard Form 298 (Rev. 8/98) Prescribed by ANSI Std. Z39, 18 Grants FA9550-04-1-0283 and FA9550-04-1-0294 Neuromorphic Modeling of Moving Target Detection...natural for neuromorphic sensory processing. We developed visual motion detection circuitry, including photodetectors, early vision, and models for both...Lincoln Labs 3DM2 run, Tanner Research reserved and utilized space corresponding to two MOSIS ’tiny chips ’ (2mm square each), each with three interconnected

  8. Moving target feature phenomenology data collection at China Lake

    Science.gov (United States)

    Gross, David C.; Hill, Jeff; Schmitz, James L.

    2002-08-01

    This paper describes the DARPA Moving Target Feature Phenomenology (MTFP) data collection conducted at the China Lake Naval Weapons Center's Junction Ranch in July 2001. The collection featured both X-band and Ku-band radars positioned on top of Junction Ranch's Parrot Peak. The test included seven targets used in eleven configurations with vehicle motion consisting of circular, straight-line, and 90-degree turning motion. Data was collected at 10-degree and 17-degree depression angles. Key parameters in the collection were polarization, vehicle speed, and road roughness. The collection also included a canonical target positioned at Junction Ranch's tilt-deck turntable. The canonical target included rotating wheels (military truck tire and civilian pick-up truck tire) and a flat plate with variable positioned corner reflectors. The canonical target was also used to simulate a rotating antenna and a vibrating plate. The target vehicles were instrumented with ARDS pods for differential GPS and roll, pitch and yaw measurements. Target motion was also documented using a video camera slaved to the X-band radar antenna and by a video camera operated near the target site.

  9. CHAOS: An SDN-Based Moving Target Defense System

    Directory of Open Access Journals (Sweden)

    Yuan Shi

    2017-01-01

    Full Text Available Moving target defense (MTD has provided a dynamic and proactive network defense to reduce or move the attack surface that is available for exploitation. However, traditional network is difficult to realize dynamic and active security defense effectively and comprehensively. Software-defined networking (SDN points out a brand-new path for building dynamic and proactive defense system. In this paper, we propose CHAOS, an SDN-based MTD system. Utilizing the programmability and flexibility of SDN, CHAOS obfuscates the attack surface including host mutation obfuscation, ports obfuscation, and obfuscation based on decoy servers, thereby enhancing the unpredictability of the networking environment. We propose the Chaos Tower Obfuscation (CTO method, which uses the Chaos Tower Structure (CTS to depict the hierarchy of all the hosts in an intranet and define expected connection and unexpected connection. Moreover, we develop fast CTO algorithms to achieve a different degree of obfuscation for the hosts in each layer. We design and implement CHAOS as an application of SDN controller. Our approach makes it very easy to realize moving target defense in networks. Our experimental results show that a network protected by CHAOS is capable of decreasing the percentage of information disclosure effectively to guarantee the normal flow of traffic.

  10. Cooperative multi-robot observation of multiple moving targets

    International Nuclear Information System (INIS)

    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

  11. Multiple operating system rotation environment moving target defense

    Science.gov (United States)

    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.

  12. Moving finite element method for ICF target implosion

    Science.gov (United States)

    Furuta, J.; Kawata, S.; Niu, K.

    1985-03-01

    One dimensional hydrodynamic codes for the analysis of internal confinement fusion (ICF) target implosion which include various effects were developed, but most of them utilize the artificial viscosity (e.g., Von Neumann's viscosity) which cannot reveal accurately the shock waves. A gain of ICF target implosion is much due to the dissipation at the shock fronts, so it is necessary to express correctly the shock waves which are affected by the viscosity. The width of the shock waves is usually a few times as large as the length of mean free path, therefore the meshes for the shock waves must be set to about 10 to the 4th to 10 to the 5th power. It is a serious problem because of the computational memories or CPU time. In the moving finite element (MPE) method, both nodal amplitudes and nodal positions move continuously with time in such a way as to satisfy simultaneous ordinary differential equations (OPDs) which minimize partial differential equation (PDE) residuals.

  13. Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

    Science.gov (United States)

    Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

    2016-12-01

    Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

  14. Inspecting rapidly moving surfaces for small defects using CNN cameras

    Science.gov (United States)

    Blug, Andreas; Carl, Daniel; Höfler, Heinrich

    2013-04-01

    A continuous increase in production speed and manufacturing precision raises a demand for the automated detection of small image features on rapidly moving surfaces. An example are wire drawing processes where kilometers of cylindrical metal surfaces moving with 10 m/s have to be inspected for defects such as scratches, dents, grooves, or chatter marks with a lateral size of 100 μm in real time. Up to now, complex eddy current systems are used for quality control instead of line cameras, because the ratio between lateral feature size and surface speed is limited by the data transport between camera and computer. This bottleneck is avoided by "cellular neural network" (CNN) cameras which enable image processing directly on the camera chip. This article reports results achieved with a demonstrator based on this novel analogue camera - computer system. The results show that computational speed and accuracy of the analogue computer system are sufficient to detect and discriminate the different types of defects. Area images with 176 x 144 pixels are acquired and evaluated in real time with frame rates of 4 to 10 kHz - depending on the number of defects to be detected. These frame rates correspond to equivalent line rates on line cameras between 360 and 880 kHz, a number far beyond the available features. Using the relation between lateral feature size and surface speed as a figure of merit, the CNN based system outperforms conventional image processing systems by an order of magnitude.

  15. A moving target for accelerated charged particle induced X-ray measurement

    International Nuclear Information System (INIS)

    Chuang, L.S.; Shima, K.; Ebihara, H.; Seki, R.; Mikumo, T.

    1980-01-01

    To attain good reproducibility as well as to enable an absolute determination in the measurement of X-ray fluorescences, resulting from bombardment of a heterogeneous sample by accelerated charged particles, a moving-target mechanism incorporating an electronic remote control system has been devised. The system is designed to scan the whole sample area with a chosen constant linear speed, by a fixed particle beam with a cross-sectional area a small fraction of that of the sample. Using 16 MeV protons and 40 MeV oxygen-ion beams, test runs of this system showed that the attempted objectives are attainable with good accuracies: reproducibility of the data for a given target is better than 3%, the linearity of the calibration curve is in good agreement, within the weighing errors of the standard elements and the uncertainty due to beam current fluctuation, with the expected values, and the results of absolute determinations using both metal foils and heterogeneous powder samples are in good agreement with accepted results using different methods. Detailed accounts of the moving-target system, and the test for reproducibility and linearity are presented. An absolute determination of the quantities related to accelerated charged-particle induced X-ray fluorescence (PIXE) using the moving target is presented for samples in different forms. (orig./HP)

  16. Small volume target for F-18 production

    Science.gov (United States)

    Pellicioli, M.; Schuler, J.; Marchand, P.; Brasse, D.

    2017-05-01

    In order to reduce the volume of O-18 enriched water used for each F-18 production for research a small volume target of 1 ml has been designed at IPHC. The designed is derived from ACSI 3.8ml F-18 target and uses both water and Helium cooling. After one year of use production yield is reported.

  17. RNA as a small molecule druggable target.

    Science.gov (United States)

    Rizvi, Noreen F; Smith, Graham F

    2017-12-01

    Small molecule drugs have readily been developed against many proteins in the human proteome, but RNA has remained an elusive target for drug discovery. Increasingly, we see that RNA, and to a lesser extent DNA elements, show a persistent tertiary structure responsible for many diverse and complex cellular functions. In this digest, we have summarized recent advances in screening approaches for RNA targets and outlined the discovery of novel, drug-like small molecules against RNA targets from various classes and therapeutic areas. The link of structure, function, and small-molecule Druggability validates now for the first time that RNA can be the targets of therapeutic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Terrestrial carbon storage dynamics: Chasing a moving target

    Science.gov (United States)

    Luo, Y.; Shi, Z.; Jiang, L.; Xia, J.; Wang, Y.; Kc, M.; Liang, J.; Lu, X.; Niu, S.; Ahlström, A.; Hararuk, O.; Hastings, A.; Hoffman, F. M.; Medlyn, B. E.; Rasmussen, M.; Smith, M. J.; Todd-Brown, K. E.; Wang, Y.

    2015-12-01

    Terrestrial ecosystems have been estimated to absorb roughly 30% of anthropogenic CO2 emissions. Past studies have identified myriad drivers of terrestrial carbon storage changes, such as fire, climate change, and land use changes. Those drivers influence the carbon storage change via diverse mechanisms, which have not been unified into a general theory so as to identify what control the direction and rate of terrestrial carbon storage dynamics. Here we propose a theoretical framework to quantitatively determine the response of terrestrial carbon storage to different exogenous drivers. With a combination of conceptual reasoning, mathematical analysis, and numeric experiments, we demonstrated that the maximal capacity of an ecosystem to store carbon is time-dependent and equals carbon input (i.e., net primary production, NPP) multiplying by residence time. The capacity is a moving target toward which carbon storage approaches (i.e., the direction of carbon storage change) but usually does not attain. The difference between the capacity and the carbon storage at a given time t is the unrealized carbon storage potential. The rate of the storage change is proportional to the magnitude of the unrealized potential. We also demonstrated that a parameter space of NPP, residence time, and carbon storage potential can well characterize carbon storage dynamics quantified at six sites ranging from tropical forests to tundra and simulated by two versions (carbon-only and coupled carbon-nitrogen) of the Australian Community Atmosphere-Biosphere Land Ecosystem (CABLE) Model under three climate change scenarios (CO2 rising only, climate warming only, and RCP8.5). Overall this study reveals the unified mechanism unerlying terrestrial carbon storage dynamics to guide transient traceability analysis of global land models and synthesis of empirical studies.

  19. Engaging a moving target: Adapting to rates of climate change

    Science.gov (United States)

    Shayegh, S.; Caldeira, K.; Moreno-Cruz, J.

    2015-12-01

    Climate change is affecting the planet and its human and natural systems at an increasing rate. As temperatures continue to rise, the international community has increasingly been considering adaptation measures to prepare for future climate change. However, most discussion around adaptation strategies has focused on preparedness for some expected amount of climate change impacts, e.g. 2 meters sea level rise. In this study, we discuss adaptation to rates of change as an alternative conceptual framework for thinking about adaptation. Adaptation is not only about adapting to amounts of change, but the rate at which these changes occur is also critically important. We ground our discussion with an example of optimal coastal investment in the face of ongoing sea level rise. Sea level rise threatens coastal assets. Finite resources could be devoted to building infrastructure further inland or to building coastal defense systems. A possible policy response could be to create a "no-build" coastal buffer zone that anticipates a future higher sea level. We present a quantitative model that illustrates the interplay among various important factors (rate of sea level rise, discount rate, capital depreciation rate, attractiveness of coastal land, etc). For some cases, strategies that combine periodic defensive investments (e.g. dikes) with planned retreat can maximize welfare when adapting to rates of climate change. In other cases, planned retreat may be optimal. It is important to prepare for ongoing increasing amounts of climate change. Preparing for a fixed amount of climate change can lead to a suboptimal solution. Climate is likely to continue changing throughout this century and beyond. To reduce adverse climate impacts, ecosystems and human systems will need to continuously adapt to a moving target.

  20. Small target detection using objectness and saliency

    Science.gov (United States)

    Zhang, Naiwen; Xiao, Yang; Fang, Zhiwen; Yang, Jian; Wang, Li; Li, Tao

    2017-10-01

    We are motived by the need for generic object detection algorithm which achieves high recall for small targets in complex scenes with acceptable computational efficiency. We propose a novel object detection algorithm, which has high localization quality with acceptable computational cost. Firstly, we obtain the objectness map as in BING[1] and use NMS to get the top N points. Then, k-means algorithm is used to cluster them into K classes according to their location. We set the center points of the K classes as seed points. For each seed point, an object potential region is extracted. Finally, a fast salient object detection algorithm[2] is applied to the object potential regions to highlight objectlike pixels, and a series of efficient post-processing operations are proposed to locate the targets. Our method runs at 5 FPS on 1000*1000 images, and significantly outperforms previous methods on small targets in cluttered background.

  1. Detection algorithm of infrared small target based on improved SUSAN operator

    Science.gov (United States)

    Liu, Xingmiao; Wang, Shicheng; Zhao, Jing

    2010-10-01

    The methods of detecting small moving targets in infrared image sequences that contain moving nuisance objects and background noise is analyzed in this paper. A novel infrared small target detection algorithm based on improved SUSAN operator is put forward. The algorithm selects double templates for the infrared small target detection: one size is greater than the small target point size and another size is equal to the small target point size. First, the algorithm uses the big template to calculate the USAN of each pixel in the image and detect the small target, the edge of the image and isolated noise pixels; Then the algorithm uses the another template to calculate the USAN of pixels detected in the first step and improves the principles of SUSAN algorithm based on the characteristics of the small target so that the algorithm can only detect small targets and don't sensitive to the edge pixels of the image and isolated noise pixels. So the interference of the edge of the image and isolate noise points are removed and the candidate target points can be identified; At last, the target is detected by utilizing the continuity and consistency of target movement. The experimental results indicate that the improved SUSAN detection algorithm can quickly and effectively detect the infrared small targets.

  2. DMPD: Fifty years of interferon research: aiming at a moving target. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available mmunity. 2006 Sep;25(3):343-8. (.png) (.svg) (.html) (.csml) Show Fifty years of interferon research: aiming at a moving target. Pubm...edID 16979566 Title Fifty years of interferon research: aiming at a moving target.

  3. Management of the interplay effect when using dynamic MLC sequences to treat moving targets

    International Nuclear Information System (INIS)

    Court, Laurence E.; Wagar, Matthew; Ionascu, Dan; Berbeco, Ross; Chin, Lee

    2008-01-01

    Interplay between organ motion and leaf motion has been shown to generally have a small dosimetric impact for most clinical intensity-modulated radiation therapy treatments. However, it has also been shown that for some MLC sequences there can be large daily variations in the delivered dose, depending on details of patient motion or the number of fractions. This study investigates guidelines for dynamic MLC sequences that will keep daily dose variations due to the interplay between organ motion and leaf motion within 10%. Dose distributions for a range of MLC separations (0.2-5.0 cm) and displacements between adjacent MLCs (0-1.5 cm) were exported from ECLIPSE to purpose-written software, which simulated the dose distribution delivered to a moving target. Target motion parallel and perpendicular to the MLC motion was investigated for a range of amplitudes (0.5-4.0 cm), periods (1.5-10 s), and MLC speeds (0.1-3.0 cm/s) with target motions modeled as sin 6 . Results were confirmed experimentally by measuring the dose delivered to an ion chamber array in a moving phantom for different MLC sequences. The simulation results were used to identify MLC sequences that kept dose variations within 10% compared to the dose delivered with no motion. The maximum allowable MLC speed, when target motion is parallel to the MLC motion, was found to be a simple function of target period and MLC separation. When the target motion is perpendicular to MLC motion, the maximum allowable MLC speed can be described as a function of MLC separation and the displacement of adjacent MLCs. These guidelines were successfully applied to two-dimensional motion, and a simple program was written to import MLC sequence files and evaluate whether the maximum daily dose discrepancy caused by the interplay effect will be larger than 10%. This software was experimentally evaluated, and found to conservatively predict whether a given MLC sequence could give large daily dose discrepancies

  4. Forward Models for Following a Moving Target with the Puma 560 Robot Manipulator

    Directory of Open Access Journals (Sweden)

    Daniel Fernando Tello Gamarra

    2015-12-01

    Full Text Available This paper describes how a forward model could be applied in a manipulator robot to accomplish the task of following a moving target. The forward model has been implemented in the puma 560 robot manipulator in simulation after a babbling motor phase using ANFIS neural networks. The forward model delivers a rough estimation of the position in the operational space of a moving target. Using this information a Cartesian controller tracks the moving target. An implementation of the proposed architecture and the Piepmeir algorithm for the problem of following a moving target is also shown in the paper. The control architecture proposed in this paper was also tested with MLP and RBF neural networks. Results and simulations are shown to demonstrate the applicability of our proposed architecture for tracking a moving target.

  5. Economic targets for small PWR reactor designs

    International Nuclear Information System (INIS)

    Board, J.

    1991-01-01

    Small reactors are likely to be less economic than large reactors, but the lower financial exposure with small reactors may be attractive to utilities contemplating a restart to a nuclear programme. New nuclear plant can be economic, but success will depend more on how the plant are built, rather than what type or size is built. A target for new plant for operation early in the next century should be a generation cost of 3p to 3.5 p/kWh. This corresponds to an overnight capital cost of Pound 1000/kWh to Pound 1100/kWh. (author)

  6. Infrared dim moving target tracking via sparsity-based discriminative classifier and convolutional network

    Science.gov (United States)

    Qian, Kun; Zhou, Huixin; Wang, Bingjian; Song, Shangzhen; Zhao, Dong

    2017-11-01

    Infrared dim and small target tracking is a great challenging task. The main challenge for target tracking is to account for appearance change of an object, which submerges in the cluttered background. An efficient appearance model that exploits both the global template and local representation over infrared image sequences is constructed for dim moving target tracking. A Sparsity-based Discriminative Classifier (SDC) and a Convolutional Network-based Generative Model (CNGM) are combined with a prior model. In the SDC model, a sparse representation-based algorithm is adopted to calculate the confidence value that assigns more weights to target templates than negative background templates. In the CNGM model, simple cell feature maps are obtained by calculating the convolution between target templates and fixed filters, which are extracted from the target region at the first frame. These maps measure similarities between each filter and local intensity patterns across the target template, therefore encoding its local structural information. Then, all the maps form a representation, preserving the inner geometric layout of a candidate template. Furthermore, the fixed target template set is processed via an efficient prior model. The same operation is applied to candidate templates in the CNGM model. The online update scheme not only accounts for appearance variations but also alleviates the migration problem. At last, collaborative confidence values of particles are utilized to generate particles' importance weights. Experiments on various infrared sequences have validated the tracking capability of the presented algorithm. Experimental results show that this algorithm runs in real-time and provides a higher accuracy than state of the art algorithms.

  7. Impact of water drops on small targets

    Science.gov (United States)

    Rozhkov, A.; Prunet-Foch, B.; Vignes-Adler, M.

    2002-10-01

    The collision of water drops against small targets was studied experimentally by means of a high-speed photography technique. The drop impact velocity was about 3.5 m/s. Drop diameters were in the range of 2.8-4.0 mm. The target was a stainless steel disk of 3.9 mm diameter. The drop spread beyond the target like a central cap surrounded by a thin, slightly conical lamella bounded by a thicker rim. By mounting a small obstacle near the target, surface-tension driven Mach waves in the flowing lamella were generated, which are formally equivalent to the familiar compressibility driven Mach waves in gas dynamics. From the measurement of the Mach angle, the values of some flow parameters could be obtained as functions of time, which provided insight into the flow structure. The liquid flowed from the central cap to the liquid rim through the thin lamella at constant momentum flux. At a certain stage of the process, most of the liquid accumulated in the rim and the internal part of the lamella became metastable. In this situation, a rupture wave propagating through the metastable internal part of the lamella caused the rim to retract while forming outwardly directed secondary jets. The jets disintegrated into secondary droplets due to the Savart-Plateau-Rayleigh instability. Prior to the end of the retraction, an internal circular wave of rupture was formed. It originated at the target and then it propagated to meet the retracting rim. Their meeting resulted in a crown of tiny droplets. A theoretical analysis of the ejection process is proposed.

  8. Moving target detection based on temporal-spatial information fusion for infrared image sequences

    Science.gov (United States)

    Toing, Wu-qin; Xiong, Jin-yu; Zeng, An-jun; Wu, Xiao-ping; Xu, Hao-peng

    2009-07-01

    Moving target detection and localization is one of the most fundamental tasks in visual surveillance. In this paper, through analyzing the advantages and disadvantages of the traditional approaches about moving target detection, a novel approach based on temporal-spatial information fusion is proposed for moving target detection. The proposed method combines the spatial feature in single frame and the temporal properties within multiple frames of an image sequence of moving target. First, the method uses the spatial image segmentation for target separation from background and uses the local temporal variance for extracting targets and wiping off the trail artifact. Second, the logical "and" operator is used to fuse the temporal and spatial information. In the end, to the fusion image sequence, the morphological filtering and blob analysis are used to acquire exact moving target. The algorithm not only requires minimal computation and memory but also quickly adapts to the change of background and environment. Comparing with other methods, such as the KDE, the Mixture of K Gaussians, etc., the simulation results show the proposed method has better validity and higher adaptive for moving target detection, especially in infrared image sequences with complex illumination change, noise change, and so on.

  9. Postural control of elderly: moving to predictable and unpredictable targets.

    NARCIS (Netherlands)

    Jongman, Vera; Lamoth, Claudine J C; van Keeken, Helco; Caljouw, Simone R

    2012-01-01

    Impaired postural control with muscle weakness is an important predictor of falls within the elderly population.Particular daily activities that require weight shifting in order to be able to reach a specific target (a cup on a table) require continuous adjustments to keep the body's center of mass

  10. c-Raf in KRas Mutant Cancers: A Moving Target.

    Science.gov (United States)

    McCormick, Frank

    2018-02-12

    Therapies for KRas cancers remain a major clinical need. In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRas G12V /Trp53 tumors, without obvious systemic toxicity and without affecting MAPK signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Moving Target Techniques: Leveraging Uncertainty for Cyber Defense

    Science.gov (United States)

    2015-12-15

    program’s source code and is not possible with proprietary, third - party software for which source code is not made available. Furthermore, ensuring...implemented in most modern operating systems including Linux, Windows, Mac OSX, Android , and iOS. By randomizing the addresses, ASLR makes exploit...applications, and software versions that are running on the target machine to develop an attack against it. During the third phase, the attacker

  12. Volume rendering in treatment planning for moving targets

    Energy Technology Data Exchange (ETDEWEB)

    Gemmel, Alexander [GSI-Biophysics, Darmstadt (Germany); Massachusetts General Hospital, Boston (United States); Wolfgang, John A.; Chen, George T.Y. [Massachusetts General Hospital, Boston (United States)

    2009-07-01

    Advances in computer technologies have facilitated the development of tools for 3-dimensional visualization of CT-data sets with volume rendering. The company Fovia has introduced a high definition volume rendering engine (HDVR trademark by Fovia Inc., Palo Alto, USA) that is capable of representing large CT data sets with high user interactivity even on standard PCs. Fovia provides a software development kit (SDK) that offers control of all the features of the rendering engine. We extended the SDK by functionalities specific to the task of treatment planning for moving tumors. This included navigation of the patient's anatomy in beam's eye view, fast point-and-click measurement of lung tumor trajectories as well as estimation of range perturbations due to motion by calculation of (differential) water equivalent path lengths for protons and carbon ions on 4D-CT data sets. We present patient examples to demonstrate the advantages and disadvantages of volume rendered images as compared to standard 2-dimensional axial plane images. Furthermore, we show an example of a range perturbation analysis. We conclude that volume rendering is a powerful technique for the representation and analysis of large time resolved data sets in treatment planning.

  13. SAR Imaging of Ground Moving Targets with Non-ideal Motion Error Compensation(in English

    Directory of Open Access Journals (Sweden)

    Zhou Hui

    2015-06-01

    Full Text Available Conventional ground moving target imaging algorithms mainly focus on the range cell migration correction and the motion parameter estimation of the moving target. However, in real Synthetic Aperture Radar (SAR data processing, non-ideal motion error compensation is also a critical process, which focuses and has serious impacts on the imaging quality of moving targets. Non-ideal motion error can not be compensated by either the stationary SAR motion error compensation algorithms or the autofocus techniques. In this paper, two sorts of non-ideal motion errors that affect the Doppler centroid of the moving target is analyzed, and a novel non-ideal motion error compensation algorithm is proposed based on the Inertial Navigation System (INS data and the range walk trajectory. Simulated and real data processing results are provided to demonstrate the effectiveness of the proposed algorithm.

  14. Schema generation in recurrent neural nets for intercepting a moving target.

    Science.gov (United States)

    Fleischer, Andreas G

    2010-06-01

    The grasping of a moving object requires the development of a motor strategy to anticipate the trajectory of the target and to compute an optimal course of interception. During the performance of perception-action cycles, a preprogrammed prototypical movement trajectory, a motor schema, may highly reduce the control load. Subjects were asked to hit a target that was moving along a circular path by means of a cursor. Randomized initial target positions and velocities were detected in the periphery of the eyes, resulting in a saccade toward the target. Even when the target disappeared, the eyes followed the target's anticipated course. The Gestalt of the trajectories was dependent on target velocity. The prediction capability of the motor schema was investigated by varying the visibility range of cursor and target. Motor schemata were determined to be of limited precision, and therefore visual feedback was continuously required to intercept the moving target. To intercept a target, the motor schema caused the hand to aim ahead and to adapt to the target trajectory. The control of cursor velocity determined the point of interception. From a modeling point of view, a neural network was developed that allowed the implementation of a motor schema interacting with feedback control in an iterative manner. The neural net of the Wilson type consists of an excitation-diffusion layer allowing the generation of a moving bubble. This activation bubble runs down an eye-centered motor schema and causes a planar arm model to move toward the target. A bubble provides local integration and straightening of the trajectory during repetitive moves. The schema adapts to task demands by learning and serves as forward controller. On the basis of these model considerations the principal problem of embedding motor schemata in generalized control strategies is discussed.

  15. Moving Beyond Motive-based categories of Targeted Violence

    Energy Technology Data Exchange (ETDEWEB)

    Weine, Stevan [Univ. of Illinois, Chicago, IL (United States); Cohen, John [Rutgers Univ., New Brunswick, NJ (United States); Brannegan, David [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-10-01

    Today’s categories for responding to targeted violence are motive-based and tend to drive policies, practices, training, media coverage, and research. These categories are based on the assumption that there are significant differences between ideological and non-ideological actors and between domestic and international actors. We question the reliance on these categories and offer an alternative way to frame the response to multiple forms of targeted violence. We propose adopting a community-based multidisciplinary approach to assess risk and provide interventions that are focused on the pre-criminal space. We describe four capabilities that should be implemented locally by establishing and maintaining multidisciplinary response teams that combine community and law-enforcement components: (1) community members are educated, making them better able to identify and report patterns associated with elevated risk for violence; (2) community-based professionals are trained to assess the risks for violent behavior posed by individuals; (3) community-based professionals learn to implement strategies that directly intervene in causal factors for those individuals who are at elevated risk; and (4) community-based professionals learn to monitor and assess an individual’s risk for violent behaviors on an ongoing basis. Community-based multidisciplinary response teams have the potential to identify and help persons in the pre-criminal space and to reduce barriers that have traditionally impeded community/law-enforcement collaboration.

  16. Biomarkers for immunotherapy in bladder cancer: a moving target.

    Science.gov (United States)

    Aggen, David H; Drake, Charles G

    2017-11-21

    Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.

  17. The search for an alerted moving target; 2005BU2-OA

    NARCIS (Netherlands)

    Vermeulen, J.F.J.; Brink, M. van den

    2005-01-01

    We investigate a two-sided, multi-stage search problem where a continuous search effort is made by one or more search units to detect a moving target in a continuous target space, under noisy detection conditions. A specific example of this problem is hunting for an enemy submarine by naval forces.

  18. Saccadic interception of a moving visual target after a spatiotemporal perturbation.

    Science.gov (United States)

    Fleuriet, Jérome; Goffart, Laurent

    2012-01-11

    Animals can make saccadic eye movements to intercept a moving object at the right place and time. Such interceptive saccades indicate that, despite variable sensorimotor delays, the brain is able to estimate the current spatiotemporal (hic et nunc) coordinates of a target at saccade end. The present work further tests the robustness of this estimate in the monkey when a change in eye position and a delay are experimentally added before the onset of the saccade and in the absence of visual feedback. These perturbations are induced by brief microstimulation in the deep superior colliculus (dSC). When the microstimulation moves the eyes in the direction opposite to the target motion, a correction saccade brings gaze back on the target path or very near. When it moves the eye in the same direction, the performance is more variable and depends on the stimulated sites. Saccades fall ahead of the target with an error that increases when the stimulation is applied more caudally in the dSC. The numerous cases of compensation indicate that the brain is able to maintain an accurate and robust estimate of the location of the moving target. The inaccuracies observed when stimulating the dSC that encodes the visual field traversed by the target indicate that dSC microstimulation can interfere with signals encoding the target motion path. The results are discussed within the framework of the dual-drive and the remapping hypotheses.

  19. SAR Ground Moving Target Indication Based on Relative Residue of DPCA Processing

    Directory of Open Access Journals (Sweden)

    Jia Xu

    2016-10-01

    Full Text Available For modern synthetic aperture radar (SAR, it has much more urgent demands on ground moving target indication (GMTI, which includes not only the point moving targets like cars, truck or tanks but also the distributed moving targets like river or ocean surfaces. Among the existing GMTI methods, displaced phase center antenna (DPCA can effectively cancel the strong ground clutter and has been widely used. However, its detection performance is closely related to the target’s signal-to-clutter ratio (SCR as well as radial velocity, and it cannot effectively detect the weak large-sized river surfaces in strong ground clutter due to their low SCR caused by specular scattering. This paper proposes a novel method called relative residue of DPCA (RR-DPCA, which jointly utilizes the DPCA cancellation outputs and the multi-look images to improve the detection performance of weak river surfaces. Furthermore, based on the statistics analysis of the RR-DPCA outputs on the homogenous background, the cell average (CA method can be well applied for subsequent constant false alarm rate (CFAR detection. The proposed RR-DPCA method can well detect the point moving targets and distributed moving targets simultaneously. Finally, the results of both simulated and real data are provided to demonstrate the effectiveness of the proposed SAR/GMTI method.

  20. Visual SLAM and Moving-object Detection for a Small-size Humanoid Robot

    Directory of Open Access Journals (Sweden)

    Yin-Tien Wang

    2010-09-01

    Full Text Available In the paper, a novel moving object detection (MOD algorithm is developed and integrated with robot visual Simultaneous Localization and Mapping (vSLAM. The moving object is assumed to be a rigid body and its coordinate system in space is represented by a position vector and a rotation matrix. The MOD algorithm is composed of detection of image features, initialization of image features, and calculation of object coordinates. Experimentation is implemented on a small-size humanoid robot and the results show that the performance of the proposed algorithm is efficient for robot visual SLAM and moving object detection.

  1. Wideband Radar Echo Frequency-domain Simulation and Analysis for High Speed Moving Targets

    Directory of Open Access Journals (Sweden)

    Ning Chao

    2014-04-01

    Full Text Available A frequency-domain method is proposed for wideband radar echo simulation of high-speed moving targets. Based on the physical process of electromagnetic waves observing a moving target, a frequency-domain echo model of wideband radar is constructed, and the block diagram of the radar echo simulation in frequency-domain is presented. Then, the impacts of radial velocity and slant range on the matching filtering of LFM radar are analyzed, and some quantitative conclusions on the shift and expansion of the radar profiles are obtained. Simulation results illustrate the correctness and efficiency of the proposed method.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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%.

  4. Numerical simulation on range of high-energy electron moving in accelerator target

    International Nuclear Information System (INIS)

    Shao Wencheng; Sun Punan; Dai Wenjiang

    2008-01-01

    In order to determine the range of high-energy electron moving in accelerator target, the range of electron with the energy range of 1 to 100 MeV moving in common target material of accelerator was calculated by Monte-Carlo method. Comparison between the calculated result and the published data were performed. The results of Monte-Carlo calculation are in good agreement with the published data. Empirical formulas were obtained for the range of high-energy electron with the energy range of 1 to 100 MeV in common target material by curve fitting, offering a series of referenced data for the design of targets in electron accelerator. (authors)

  5. An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

    Science.gov (United States)

    Aleksandrova, I. V.; Bazdenkov, S. V.; Chtcherbakov, V. I.; Gromov, A. I.; Koresheva, E. R.; Koshelev, E. A.; Osipov, I. E.; Yaguzinskiy, L. S.

    2004-04-01

    Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets.

  6. An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

    International Nuclear Information System (INIS)

    Aleksandrova, I V; Bazdenkov, S V; Chtcherbakov, V I; Gromov, A I; Koresheva, E R; Koshelev, E A; Osipov, I E; Yaguzinskiy, L S

    2004-01-01

    Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets

  7. Electrostatics, small particles, and laser fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1978-01-01

    The success of any Inertial Confinement Fusion system for the production of useful power depends critically on the production of suitable targets. This is true whether the arrangement is that proposed by Nuckolls et al. or some other arrangement. The target must have characteristics such as material composition, structure, and surface finish which are tailored to the laser pulse length, energy, peak and average power and pulse shape. To provide useful power on a continuous basis, it is likely that the repetition rate will be 1.0 to 10 per second. Thus, in a 24 hour running period 864,000 targets may be necessary and one must be placed at the focal point of the laser every tenth of a second. For economic operation it is necessary that the targets be produced at costs of less than $1.00 per target

  8. IMRT delivery to a moving target by dynamic MLC tracking: delivery for targets moving in two dimensions in the beam's eye view

    International Nuclear Information System (INIS)

    McQuaid, D; Webb, S

    2006-01-01

    A new modification of the dynamic multileaf collimator (dMLC) delivery technique for intensity-modulated therapy (IMRT) is outlined. This technique enables the tracking of a target moving through rigid-body translations in a 2D trajectory in the beam's eye view. The accuracy of the delivery versus that of deliveries with no tracking and of 1D tracking techniques is quantified with clinically derived intensity-modulated beams (IMBs). Leaf trajectories calculated in the target-reference frame were iteratively synchronized assuming regular target motion. This allowed the leaves defined in the lab-reference frame to simultaneously follow the target motion and to deliver the required IMB without violation of the leaf maximum-velocity constraint. The leaves are synchronized until the gradient of the leaf position at every instant is less than a calculated maximum. The delivered fluence in the target-reference frame was calculated with a simple primary-fluence model. The new 2D tracking technique was compared with the delivered fluence produced by no-tracking deliveries and by 1D tracking deliveries for 33 clinical IMBs. For the clinical IMBs normalized to a maximum fluence of 200 MUs, the rms difference between the desired and the delivered IMB was 15.6 ± 3.3 MU for the case of a no-tracking delivery, 7.9 ± 1.6 MU for the case where only the primary component of motion was corrected and 5.1 ± 1.1 MU for the 2D tracking delivery. The residual error is due to interpolation and sampling effects. The 2D tracking delivery technique requires an increase in the delivery time evaluated as between 0 and 50% of the unsynchronized delivery time for each beam with a mean increase of 13% for the IMBs tested. The 2D tracking dMLC delivery technique allows an optimized IMB to be delivered to moving targets with increased accuracy and with acceptable increases in delivery time. When combined with real-time knowledge of the target motion at delivery time, this technique facilitates

  9. Saccadic foveation of a moving visual target in the rhesus monkey.

    Science.gov (United States)

    Fleuriet, Jérome; Hugues, Sandrine; Perrinet, Laurent; Goffart, Laurent

    2011-02-01

    When generating a saccade toward a moving target, the target displacement that occurs during the period spanning from its detection to the saccade end must be taken into account to accurately foveate the target and to initiate its pursuit. Previous studies have shown that these saccades are characterized by a lower peak velocity and a prolonged deceleration phase. In some cases, a second peak eye velocity appears during the deceleration phase, presumably reflecting the late influence of a mechanism that compensates for the target displacement occurring before saccade end. The goal of this work was to further determine in the head restrained monkey the dynamics of this putative compensatory mechanism. A step-ramp paradigm, where the target motion was orthogonal to a target step occurring along the primary axes, was used to estimate from the generated saccades: a component induced by the target step and another one induced by the target motion. Resulting oblique saccades were compared with saccades to a static target with matched horizontal and vertical amplitudes. This study permitted to estimate the time taken for visual motion-related signals to update the programming and execution of saccades. The amplitude of the motion-related component was slightly hypometric with an undershoot that increased with target speed. Moreover, it matched with the eccentricity that the target had 40-60 ms before saccade end. The lack of significant difference in the delay between the onsets of the horizontal and vertical components between saccades directed toward a static target and those aimed at a moving target questions the late influence of the compensatory mechanism. The results are discussed within the framework of the "dual drive" and "remapping" hypotheses.

  10. Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB Radar Systems

    Directory of Open Access Journals (Sweden)

    Jana Rovňáková

    2013-09-01

    Full Text Available In the case of through-the-wall localization of moving targets by ultra wideband (UWB radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

  11. Low-resolution Airborne Radar Air/ground Moving Target Classification and Recognition

    Directory of Open Access Journals (Sweden)

    Wang Fu-you

    2014-10-01

    Full Text Available Radar Target Recognition (RTR is one of the most important needs of modern and future airborne surveillance radars, and it is still one of the key technologies of radar. The majority of present algorithms are based on wide-band radar signal, which not only needs high performance radar system and high target Signal-to-Noise Ratio (SNR, but also is sensitive to angle between radar and target. Low-Resolution Airborne Surveillance Radar (LRASR in downward-looking mode, slow flying aircraft and ground moving truck have similar Doppler velocity and Radar Cross Section (RCS, leading to the problem that LRASR air/ground moving targets can not be distinguished, which also disturbs detection, tracking, and classification of low altitude slow flying aircraft to solve these issues, an algorithm based on narrowband fractal feature and phase modulation feature is presented for LRASR air/ground moving targets classification. Real measured data is applied to verify the algorithm, the classification results validate the proposed method, helicopters and truck can be well classified, the average discrimination rate is more than 89% when SNR ≥ 15 dB.

  12. Study on moving target detection to passive radar based on FM broadcast transmitter

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Target detection by a noncooperative illuminator is a topic of general interest in the electronic warfare field.First of all,direct-path interference(DPI)suppression which is the technique of bottleneck of moving target detection by a noncooperative frequency modulation(FM) broadcast transmitter is analyzed in this article;Secondly,a space-time-frequency domain synthetic solution to this problem is introduced:Adaptive nulling array processing is considered in the space domain,DPI cancellation based on adaptive fractional delay interpolation(AFDI)technique is used in planned time domain,and long-time coherent integration is utilized in the frequency domain;Finally,an experimental system is planned by considering FM broadcast transmitter as a noncooperative illuminator,Simulation results by real collected data show that the proposed method has a better performance of moving target detection.

  13. Familiar trajectories facilitate the interpretation of physical forces when intercepting a moving target.

    Science.gov (United States)

    Mijatović, Antonija; La Scaleia, Barbara; Mercuri, Nicola; Lacquaniti, Francesco; Zago, Myrka

    2014-12-01

    Familiarity with the visual environment affects our expectations about the objects in a scene, aiding in recognition and interaction. Here we tested whether the familiarity with the specific trajectory followed by a moving target facilitates the interpretation of the effects of underlying physical forces. Participants intercepted a target sliding down either an inclined plane or a tautochrone. Gravity accelerated the target by the same amount in both cases, but the inclined plane represented a familiar trajectory whereas the tautochrone was unfamiliar to the participants. In separate sessions, the gravity field was consistent with either natural gravity or artificial reversed gravity. Target motion was occluded from view over the last segment. We found that the responses in the session with unnatural forces were systematically delayed relative to those with natural forces, but only for the inclined plane. The time shift is consistent with a bias for natural gravity, in so far as it reflects an a priori expectation that a target not affected by natural forces will arrive later than one accelerated downwards by gravity. Instead, we did not find any significant time shift with unnatural forces in the case of the tautochrone. We argue that interception of a moving target relies on the integration of the high-level cue of trajectory familiarity with low-level cues related to target kinematics.

  14. Metallic beryllium-7 target of small diameter

    CERN Document Server

    Zyuzin, A Yu; Vincent, J S; Buckley, K R; Bateman, N P; Snover, K A; Csandjan, J M; Steiger, T D; Adelberger, E G; Swanson, H E

    1999-01-01

    The stellar sup 7 Be(p, gamma) sup 8 B reaction rate has the largest uncertainty among all nuclear reaction rates in the standard solar model. However, the solar neutrino flux predicted for the majority of proposed and existing solar neutrino detectors is directly dependent on the rate of sup 7 Be(p, gamma) sup 8 B reaction. The existing solar neutrino detectors measure rate of sup 8 B decay neutrinos that is too low. This constitutes largely the solar neutrino problem. Existing measurements of the sup 7 Be(p, gamma) sup 8 B reaction rate disagree with one another, indicating the need for more precise experiments. To provide the required targets a new procedure for sup 7 Be production, separation and target manufacturing has been developed. First, a lithium target has been designed for sup 7 Be production at TRIUMF's 13 MeV cyclotron. The lithium target has been extensively tested at 50 mu A proton beam current yielding 8.1 MBq/mu A h of sup 7 Be. An adsorption filtration technique has been developed for sup ...

  15. Targeting and localized signalling by small GTPases

    NARCIS (Netherlands)

    ten Klooster, Jean Paul; Hordijk, Peter L.

    2007-01-01

    Polarized cellular responses, for example, cell migration, require the co-ordinated assembly of signalling complexes at a particular subcellular location, such as the leading edge of cells. Small GTPases of the Ras superfamily play central roles in many (polarized) responses to growth factors,

  16. Ultrasound image based visual servoing for moving target ablation by high intensity focused ultrasound.

    Science.gov (United States)

    Seo, Joonho; Koizumi, Norihiro; Mitsuishi, Mamoru; Sugita, Naohiko

    2017-12-01

    Although high intensity focused ultrasound (HIFU) is a promising technology for tumor treatment, a moving abdominal target is still a challenge in current HIFU systems. In particular, respiratory-induced organ motion can reduce the treatment efficiency and negatively influence the treatment result. In this research, we present: (1) a methodology for integration of ultrasound (US) image based visual servoing in a HIFU system; and (2) the experimental results obtained using the developed system. In the visual servoing system, target motion is monitored by biplane US imaging and tracked in real time (40 Hz) by registration with a preoperative 3D model. The distance between the target and the current HIFU focal position is calculated in every US frame and a three-axis robot physically compensates for differences. Because simultaneous HIFU irradiation disturbs US target imaging, a sophisticated interlacing strategy was constructed. In the experiments, respiratory-induced organ motion was simulated in a water tank with a linear actuator and kidney-shaped phantom model. Motion compensation with HIFU irradiation was applied to the moving phantom model. Based on the experimental results, visual servoing exhibited a motion compensation accuracy of 1.7 mm (RMS) on average. Moreover, the integrated system could make a spherical HIFU-ablated lesion in the desired position of the respiratory-moving phantom model. We have demonstrated the feasibility of our US image based visual servoing technique in a HIFU system for moving target treatment. © 2016 The Authors The International Journal of Medical Robotics and Computer Assisted Surgery Published by John Wiley & Sons Ltd.

  17. Small Surface Target Detection with EO/IR Sensors

    NARCIS (Netherlands)

    Jong, A.N. de; Kemp, R.A.W.

    1998-01-01

    The detection of small surface targets at sea is an increasing requirement for warships. The present sensors on board do not provide the required detection probabilities for these low observable targets like small rubber boats, floating mines, periscopes, people etc. The reason for the low

  18. Application of Fractional Fourier Transform to Moving Target Indication via Along-Track Interferometry

    Directory of Open Access Journals (Sweden)

    Chiu Shen

    2005-01-01

    Full Text Available A relatively unknown yet powerful technique, the so-called fractional Fourier transform (FrFT, is applied to SAR along-track interferometry (SAR-ATI in order to estimate moving target parameters. By mapping a target's signal onto a fractional Fourier axis, the FrFT permits a constant-velocity target to be focused in the fractional Fourier domain thereby affording orders of magnitude improvement in SCR. Moving target velocity and position parameters are derived and expressed in terms of an optimum fractional angle and a measured fractional Fourier position , allowing a target to be accurately repositioned and its velocity components computed without actually forming an SAR image. The new estimation algorithm is compared with the matched filter bank approach, showing some of the advantages of the FrFT method. The proposed technique is applied to the data acquired by the two-aperture CV580 airborne radar system configured in its along-track mode. Results show that the method is effective in estimating target velocity and position parameters.

  19. Deployment Design of Wireless Sensor Network for Simple Multi-Point Surveillance of a Moving Target

    Science.gov (United States)

    Tsukamoto, Kazuya; Ueda, Hirofumi; Tamura, Hitomi; Kawahara, Kenji; Oie, Yuji

    2009-01-01

    In this paper, we focus on the problem of tracking a moving target in a wireless sensor network (WSN), in which the capability of each sensor is relatively limited, to construct large-scale WSNs at a reasonable cost. We first propose two simple multi-point surveillance schemes for a moving target in a WSN and demonstrate that one of the schemes can achieve high tracking probability with low power consumption. In addition, we examine the relationship between tracking probability and sensor density through simulations, and then derive an approximate expression representing the relationship. As the results, we present guidelines for sensor density, tracking probability, and the number of monitoring sensors that satisfy a variety of application demands. PMID:22412326

  20. DMLC motion tracking of moving targets for intensity modulated arc therapy treatment

    DEFF Research Database (Denmark)

    Zimmerman, Jens; Korreman, Stine; Persson, Gitte

    2009-01-01

    (DMLC). The aim of this work was to evaluate the dose delivered to moving targets using the RapidArc (Varian Medical Systems, Inc.) technology with and without a DMLC tracking algorithm. MATERIAL AND METHODS: A Varian Clinac iX was equipped with a preclinical RapidArc and a 3D DMLC tracking application......) and state (1). CONCLUSIONS: DMLC tracking together with RapidArc make a feasible combination and is capable of improving the dose distribution delivered to a moving target. It seems to be of importance to minimize noise influencing the tracking, to gain the full benefit from the application........ A motion platform was placed on the couch, with the detectors on top: a PTW seven29 and a Scandidos Delta4. One lung plan and one prostate plan were delivered. Motion was monitored using a Real-time Position Management (RPM) system. Reference measurements were performed for both plans with both detectors...

  1. Optical characterisation of small surface targets

    CSIR Research Space (South Africa)

    Schwering, PBW

    2007-09-01

    Full Text Available , 3, 5 km distance from IMT (Institute for Maritime Technology) in Simon’ Town, in-bound head-on runs, as well as in-bound and out-bound weaving zig-zag runs. Target positions were accurately measured with a Differential GPS (DGPS) system. In some... to sea spray generated by the boat’s pitching action going through the sea swells (more pronounced at longer ranger). 4. BACKGROUND CLUTTER Of major interest in development of automatic detection and classification systems is the signal processing...

  2. A new method of small target detection based on neural network

    Science.gov (United States)

    Hu, Jing; Hu, Yongli; Lu, Xinxin

    2018-02-01

    The detection and tracking of moving dim target in infrared image have been an research hotspot for many years. The target in each frame of images only occupies several pixels without any shape and structure information. Moreover, infrared small target is often submerged in complicated background with low signal-to-clutter ratio, making the detection very difficult. Different backgrounds exhibit different statistical properties, making it becomes extremely complex to detect the target. If the threshold segmentation is not reasonable, there may be more noise points in the final detection, which is unfavorable for the detection of the trajectory of the target. Single-frame target detection may not be able to obtain the desired target and cause high false alarm rate. We believe the combination of suspicious target detection spatially in each frame and temporal association for target tracking will increase reliability of tracking dim target. The detection of dim target is mainly divided into two parts, In the first part, we adopt bilateral filtering method in background suppression, after the threshold segmentation, the suspicious target in each frame are extracted, then we use LSTM(long short term memory) neural network to predict coordinates of target of the next frame. It is a brand-new method base on the movement characteristic of the target in sequence images which could respond to the changes in the relationship between past and future values of the values. Simulation results demonstrate proposed algorithm can effectively predict the trajectory of the moving small target and work efficiently and robustly with low false alarm.

  3. Detection of Fast Moving and Accelerating Targets Compensating Range and Doppler Migration

    Science.gov (United States)

    2014-06-01

    TR–2978 UNCLASSIFIED the chirp bandwidth is changed from pulse to pulse to realise the range migration com- pensation. Also, Dai et. al. [11] proposed...injected at different closing velocities and acceleration values . Figure 1(a) shows the range-Doppler map of a non-accelarating target moving at 100 knots...increase the noise floor. Hence, consideration must be given to establish a criteria for the combination processing to achieve a net SNR improvement for a

  4. Does the Brain Extrapolate the Position of a Transient Moving Target?

    Science.gov (United States)

    Quinet, Julie; Goffart, Laurent

    2015-08-26

    When an object moves in the visual field, its motion evokes a streak of activity on the retina and the incoming retinal signals lead to robust oculomotor commands because corrections are observed if the trajectory of the interceptive saccade is perturbed by a microstimulation in the superior colliculus. The present study complements a previous perturbation study by investigating, in the head-restrained monkey, the generation of saccades toward a transient moving target (100-200 ms). We tested whether the saccades land on the average of antecedent target positions or beyond the location where the target disappeared. Using target motions with different speed profiles, we also examined the sensitivity of the process that converts time-varying retinal signals into saccadic oculomotor commands. The results show that, for identical overall target displacements on the visual display, saccades toward a faster target land beyond the endpoint of saccades toward a target moving slower. The rate of change in speed matters in the visuomotor transformation. Indeed, in response to identical overall target displacements and durations, the saccades have smaller amplitude when they are made in response to an accelerating target than to a decelerating one. Moreover, the motion-related signals have different weights depending upon their timing relative to the target onset: early signals are more influential in the specification of saccade amplitude than later signals. We discuss the "predictive" properties of the visuo-saccadic system and the nature of this location where the saccades land, after providing some critical comments to the "hic-et-nunc" hypothesis (Fleuriet and Goffart, 2012). Complementing the work of Fleuriet and Goffart (2012), this study is a contribution to the more general scientific research aimed at understanding how ongoing action is dynamically and adaptively adjusted to the current spatiotemporal aspects of its goal. Using the saccadic eye movement as a probe

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

    Directory of Open Access Journals (Sweden)

    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. Spot Weight Adaptation for Moving Target in Spot Scanning Proton Therapy.

    Science.gov (United States)

    Morel, Paul; Wu, Xiaodong; Blin, Guillaume; Vialette, Stéphane; Flynn, Ryan; Hyer, Daniel; Wang, Dongxu

    2015-01-01

    This study describes a real-time spot weight adaptation method in spot-scanning proton therapy for moving target or moving patient, so that the resultant dose distribution closely matches the planned dose distribution. The method proposed in this study adapts the weight (MU) of the delivering pencil beam to that of the target spot; it will actually hit during patient/target motion. The target spot that a certain delivering pencil beam may hit relies on patient monitoring and/or motion modeling using four-dimensional (4D) CT. After the adapted delivery, the required total weight [Monitor Unit (MU)] for this target spot is then subtracted from the planned value. With continuous patient motion and continuous spot scanning, the planned doses to all target spots will eventually be all fulfilled. In a proof-of-principle test, a lung case was presented with realistic temporal and motion parameters; the resultant dose distribution using spot weight adaptation was compared to that without using this method. The impact of the real-time patient/target position tracking or prediction was also investigated. For moderate motion (i.e., mean amplitude 0.5 cm), D95% to the planning target volume (PTV) was only 81.5% of the prescription (RX) dose; with spot weight adaptation PTV D95% achieves 97.7% RX. For large motion amplitude (i.e., 1.5 cm), without spot weight adaptation PTV D95% is only 42.9% of RX; with spot weight adaptation, PTV D95% achieves 97.7% RX. Larger errors in patient/target position tracking or prediction led to worse final target coverage; an error of 3 mm or smaller in patient/target position tracking is preferred. The proposed spot weight adaptation method was able to deliver the planned dose distribution and maintain target coverage when patient motion was involved. The successful implementation of this method would rely on accurate monitoring or prediction of patient/target motion.

  7. Spot Weight Adaptation for Moving Target in Spot Scanning Proton Therapy

    Directory of Open Access Journals (Sweden)

    Paul eMorel

    2015-05-01

    Full Text Available Purpose: This study describes a real-time spot weight adaptation method in spot-scanning proton therapy for moving target or moving patient, so that the resultant dose distribution closely matches the planned dose distribution. Materials and Methods: The method proposed in this study adapts the weight (MU of the delivering pencil beam to that of the target spot it will actually hit during patient/target motion. The target spot a certain delivering pencil beam may hit relies on patient monitoring and/or motion modeling using four-dimensional (4D CT. After the adapted delivery, the required total weight (MU for this target spot is then subtracted from the planned value. With continuous patient motion and continuous spot scanning, the planned doses to all target spots will eventually be all fulfilled. In a proof-of-principle test, a lung case was presented with realistic temporal and motion parameters; the resultant dose distribution using spot weight adaptation was compared to that without using this method. The impact of the real-time patient/target position tracking or prediction was also investigated.Results: For moderate motion (i.e., mean amplitude 0.5 cm, D95% to the planning target volume (PTV was only 81.5% of the prescription (RX dose; with spot weight adaptation PTV D95% achieves 97.7%RX. For large motion amplitude (i.e., 1.5 cm, without spot weight adaptation PTV D95% is only 42.9% of RX; with spot weight adaptation, PTV D95% achieves 97.7%RX. Larger errors in patient/target position tracking or prediction led to worse final target coverage; an error of 3mm or smaller in patient/target position tracking is preferred. Conclusion: The proposed spot weight adaptation method was able to deliver the planned dose distribution and maintain target coverage when patient motion was involved. The successful implementation of this method would rely on accurate monitoring or prediction of patient/target motion.

  8. Recent advances in developing small molecules targeting RNA.

    Science.gov (United States)

    Guan, Lirui; Disney, Matthew D

    2012-01-20

    RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

  9. Detection of Moving Targets Based on Doppler Spectrum Analysis Technique for Passive Coherent Radar

    Directory of Open Access Journals (Sweden)

    Zhao Yao-dong

    2013-06-01

    Full Text Available A novel method of moving targets detection taking Doppler spectrum analysis technique for Passive Coherent Radar (PCR is provided. After dividing the receiving signals into segments as pulse series, it utilizes the technique of pulse compress and Doppler processing to detect and locate the targets. Based on the algorithm for Pulse-Doppler (PD radar, the equipollence between continuous and pulsed wave in match filtering is proved and details of this method are introduced. To compare it with the traditional method of Cross-Ambiguity Function (CAF calculation, the relationship and mathematical modes of them are analyzed, with some suggestions on parameters choosing. With little influence to the gain of targets, the method can greatly promote the processing efficiency. The validity of the proposed method is demonstrated by offline processing real collected data sets and simulation results.

  10. Performance Evaluation of Moving Small-Cell Network with Proactive Cache

    Directory of Open Access Journals (Sweden)

    Young Min Kwon

    2016-01-01

    Full Text Available Due to rapid growth in mobile traffic, mobile network operators (MNOs are considering the deployment of moving small-cells (mSCs. mSC is a user-centric network which provides voice and data services during mobility. mSC can receive and forward data traffic via wireless backhaul and sidehaul links. In addition, due to the predictive nature of users demand, mSCs can proactively cache the predicted contents in off-peak-traffic periods. Due to these characteristics, MNOs consider mSCs as a cost-efficient solution to not only enhance the system capacity but also provide guaranteed quality of service (QoS requirements to moving user equipment (UE in peak-traffic periods. In this paper, we conduct extensive system level simulations to analyze the performance of mSCs with varying cache size and content popularity and their effect on wireless backhaul load. The performance evaluation confirms that the QoS of moving small-cell UE (mSUE notably improves by using mSCs together with proactive caching. We also show that the effective use of proactive cache significantly reduces the wireless backhaul load and increases the overall network capacity.

  11. Estimation of direction of arrival of a moving target using subspace based approaches

    Science.gov (United States)

    Ghosh, Ripul; Das, Utpal; Akula, Aparna; Kumar, Satish; Sardana, H. K.

    2016-05-01

    In this work, array processing techniques based on subspace decomposition of signal have been evaluated for estimation of direction of arrival of moving targets using acoustic signatures. Three subspace based approaches - Incoherent Wideband Multiple Signal Classification (IWM), Least Square-Estimation of Signal Parameters via Rotation Invariance Techniques (LS-ESPRIT) and Total Least Square- ESPIRIT (TLS-ESPRIT) are considered. Their performance is compared with conventional time delay estimation (TDE) approaches such as Generalized Cross Correlation (GCC) and Average Square Difference Function (ASDF). Performance evaluation has been conducted on experimentally generated data consisting of acoustic signatures of four different types of civilian vehicles moving in defined geometrical trajectories. Mean absolute error and standard deviation of the DOA estimates w.r.t. ground truth are used as performance evaluation metrics. Lower statistical values of mean error confirm the superiority of subspace based approaches over TDE based techniques. Amongst the compared methods, LS-ESPRIT indicated better performance.

  12. RNA targeting by small molecules: Binding of protoberberine ...

    Indian Academy of Sciences (India)

    2012-06-25

    Jun 25, 2012 ... Studies on RNA targeting by small molecules to specifically control certain cellular functions is an .... form secondary structures such as stem-loop, hairpin, etc. ..... paired third strand of the triplex without affecting the stability.

  13. Small target pre-detection with an attention mechanism

    Science.gov (United States)

    Wang, Yuehuan; Zhang, Tianxu; Wang, Guoyou

    2002-04-01

    We introduce the concept of predetection based on an attention mechanism to improve the efficiency of small-target detection by limiting the image region of detection. According to the characteristics of small-target detection, local contrast is taken as the only feature in predetection and a nonlinear sampling model is adopted to make the predetection adaptive to detect small targets with different area sizes. To simplify the predetection itself and decrease the false alarm probability, neighboring nodes in the sampling grid are used to generate a saliency map, and a short-term memory is adopted to accelerate the `pop-out' of targets. We discuss the fact that the proposed approach is simple enough in computational complexity. In addition, even in a cluttered background, attention can be led to targets in a satisfying few iterations, which ensures that the detection efficiency will not be decreased due to false alarms. Experimental results are presented to demonstrate the applicability of the approach.

  14. Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

    LENUS (Irish Health Repository)

    Gasch, Claudia

    2017-01-01

    It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

  15. Slower resting alpha frequency is associated with superior localisation of moving targets.

    Science.gov (United States)

    Howard, Christina J; Arnold, Craig P A; Belmonte, Matthew K

    2017-10-01

    We examined the neurophysiological underpinnings of individual differences in the ability to maintain up-to-date representations of the positions of moving objects. In two experiments similar to the multiple object tracking (MOT) task, we asked observers to monitor continuously one or several targets as they moved unpredictably for a semi-random period. After all objects disappeared, observers were immediately prompted to report the perceived final position of one queried target. Precision of these position reports declined with attentional load, and reports tended to best resemble positions occupied by the queried target between 0 and 30ms in the past. Measurement of event-related potentials showed a contralateral delay activity over occipital scalp, maximal in the right hemisphere. The peak power-spectral frequency of observers' eyes-closed resting occipital alpha oscillations reliably predicted performance, such that lower-frequency alpha was associated with superior spatial localisation. Slower resting alpha might be associated with a cognitive style that depends less on memory-related processing and instead emphasises attention to changing stimuli. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  16. The importance of surrounding tissues and window settings for contouring of moving targets

    Energy Technology Data Exchange (ETDEWEB)

    Borm, Kai Joachim [Technische Universitaet Muenchen, Medical School, Munich (Germany); Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Oechsner, Markus; Berndt, Johannes; Combs, Stephanie Elisabeth; Molls, Michael; Duma, Marciana Nona [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany)

    2015-09-15

    The aim of the study was to assess the importance of surrounding tissues for the delineation of moving targets in tissue-specific phantoms and to find optimal settings for lung, soft tissue, and liver tumors. Tumor movement was simulated by a water-filled table tennis ball (target volume, TV). Three phantoms were created: corkboards to simulate lung tissue (lung phantom, LunPh), animal fat as fatty soft tissue (fatty tissue phantom, FatPh), and water enhanced with contrast medium as the liver tissue (liver phantom, LivPh). Slow planning three-dimensional compute tomography images (3D-CTs) were acquired with and without phantom movements. One-dimensional tumor movement (1D), three-dimensional tumor movement (3D), as well as a real patient's tumor trajectories were simulated. The TV was contoured using two lung window settings, two soft-tissue window settings, and one liver window setting. The volumes were compared to mathematical calculated values. TVs were underestimated in all phantoms due to movement. The use of soft-tissue windows in the LivPh led to a significantunderestimation of the TV (70.8 % of calculated TV). When common window settings [LunPh + 200 HU/-1,000 HU (upper window/lower window threshold); FatPh: + 240 HU/-120 HU; LivPh: + 175 HU/+ 50 HU] were used, the contoured TVs were: LivPh, 84.0 %; LunPh, 93.2 %, and FatPh, 92.8 %. The lower window threshold had a significant impact on the size of the delineated TV, whereas changes of the upper threshold led only to small differences. The decisive factor for window settings is the lower window threshold (for adequate TV delineation in the lung and fatty-soft tissue it should be lower than density values of surrounding tissue). The use of a liver window should be considered. (orig.) [German] Das Ziel dieser Arbeit war es, den Einfluss des umgebenden Gewebes auf die Konturierung bewegter Objekte zu untersuchen. Um die optimalen CT-Fensterungen fuer Lungen-, Weichteil- und Lebertumoren zu bestimmen

  17. Implosion of the small cavity and large cavity cannonball targets

    International Nuclear Information System (INIS)

    Nishihara, Katsunobu; Yamanaka, Chiyoe.

    1984-01-01

    Recent results of cannonball target implosion research are briefly reviewed with theoretical predictions for GEKKO XII experiments. The cannonball targets are classified into two types according to the cavity size ; small cavity and large cavity. The compression mechanisms of the two types are discussed. (author)

  18. Liquid-4He target with a small refrigerator

    International Nuclear Information System (INIS)

    Kato, S.; Kitami, T.; Maruyama, K.; Murata, Y.; Endo, S.; Niki, K.; Morita, T.

    1989-10-01

    A liquid- 4 He target system with a small refrigerator has been developed for the first time to study γ 4 He reactions at intermediate energies. The density of the target is controlled within an accuracy of 3 %. The target system has been operated successfully for more than 1,000 hours of the experiment using the π-sr TAGX spectrometer at the 1.3-GeV Tokyo electron synchrotron. (author)

  19. FrFT-CSWSF: Estimating cross-range velocities of ground moving targets using multistatic synthetic aperture radar

    Directory of Open Access Journals (Sweden)

    Li Chenlei

    2014-10-01

    Full Text Available Estimating cross-range velocity is a challenging task for space-borne synthetic aperture radar (SAR, which is important for ground moving target indication (GMTI. Because the velocity of a target is very small compared with that of the satellite, it is difficult to correctly estimate it using a conventional monostatic platform algorithm. To overcome this problem, a novel method employing multistatic SAR is presented in this letter. The proposed hybrid method, which is based on an extended space-time model (ESTIM of the azimuth signal, has two steps: first, a set of finite impulse response (FIR filter banks based on a fractional Fourier transform (FrFT is used to separate multiple targets within a range gate; second, a cross-correlation spectrum weighted subspace fitting (CSWSF algorithm is applied to each of the separated signals in order to estimate their respective parameters. As verified through computer simulation with the constellations of Cartwheel, Pendulum and Helix, this proposed time-frequency-subspace method effectively improves the estimation precision of the cross-range velocities of multiple targets.

  20. Dynamical scene analysis with a moving camera: mobile targets detection system

    International Nuclear Information System (INIS)

    Hennebert, Christine

    1996-01-01

    This thesis work deals with the detection of moving objects in monocular image sequences acquired with a mobile camera. We propose a method able to detect small moving objects in visible or infrared images of real outdoor scenes. In order to detect objects of very low apparent motion, we consider an analysis on a large temporal interval. We have chosen to compensate for the dominant motion due to the camera displacement for several consecutive images in order to form a sub-sequence of images for which the camera seems virtually static. We have also developed a new approach allowing to extract the different layers of a real scene in order to deal with cases where the 2D motion due to the camera displacement cannot be globally compensated for. To this end, we use a hierarchical model with two levels: the local merging step and the global merging one. Then, an appropriate temporal filtering is applied to registered image sub-sequence to enhance signals corresponding to moving objects. The detection issue is stated as a labeling problem within a statistical regularization based on Markov Random Fields. Our method has been validated on numerous real image sequences depicting complex outdoor scenes. Finally, the feasibility of an integrated circuit for mobile object detection has been proved. This circuit could lead to an ASIC creation. (author) [fr

  1. Remote-controlled flexible pose measurement system and method for a moving target in wind tunnel

    Directory of Open Access Journals (Sweden)

    Wei LIU

    2018-01-01

    Full Text Available The measurement of position and attitude parameters for the isolated target from a high-speed aircraft is a great challenge in the field of wind tunnel simulation technology. This paper proposes a remote-controlled flexible pose measurement system in wind tunnel conditions for the separation of a target from an aircraft. The position and attitude parameters of a moving object are obtained by utilizing a single camera with a focal length and camera orientation that can be changed based on different measurement conditions. Using this proposed system and method, both the flexibility and efficiency of the pose measurement system can be enhanced in wind tunnel conditions to meet the measurement requirements of different objects and experiments, which is also useful for the development of an intelligent position and attitude measurement system. The position and the focal length of the camera also can be controlled remotely during measurements to enlarge both the vertical and horizontal measurement range of this system. Experiments are conducted in the laboratory to measure the position and attitude of moving objects with high flexibility and efficiency, and the measurement precision of the measurement system is also verified through experiments.

  2. Final Report for Bio-Inspired Approaches to Moving-Target Defense Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Glenn A.; Oehmen, Christopher S.

    2012-09-01

    This report records the work and contributions of the NITRD-funded Bio-Inspired Approaches to Moving-Target Defense Strategies project performed by Pacific Northwest National Laboratory under the technical guidance of the National Security Agency’s R6 division. The project has incorporated a number of bio-inspired cyber defensive technologies within an elastic framework provided by the Digital Ants. This project has created the first scalable, real-world prototype of the Digital Ants Framework (DAF)[11] and integrated five technologies into this flexible, decentralized framework: (1) Ant-Based Cyber Defense (ABCD), (2) Behavioral Indicators, (3) Bioinformatic Clas- sification, (4) Moving-Target Reconfiguration, and (5) Ambient Collaboration. The DAF can be used operationally to decentralize many such data intensive applications that normally rely on collection of large amounts of data in a central repository. In this work, we have shown how these component applications may be decentralized and may perform analysis at the edge. Operationally, this will enable analytics to scale far beyond current limitations while not suffering from the bandwidth or computational limitations of centralized analysis. This effort has advanced the R6 Cyber Security research program to secure digital infrastructures by developing a dynamic means to adaptively defend complex cyber systems. We hope that this work will benefit both our client’s efforts in system behavior modeling and cyber security to the overall benefit of the nation.

  3. Location detection and tracking of moving targets by a 2D IR-UWB radar system.

    Science.gov (United States)

    Nguyen, Van-Han; Pyun, Jae-Young

    2015-03-19

    In indoor environments, the Global Positioning System (GPS) and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB) technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB) radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF) is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

  4. Location Detection and Tracking of Moving Targets by a 2D IR-UWB Radar System

    Directory of Open Access Journals (Sweden)

    Van-Han Nguyen

    2015-03-01

    Full Text Available In indoor environments, the Global Positioning System (GPS and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

  5. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

    Science.gov (United States)

    Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

    2004-12-01

    HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

  6. Small Moves, NUI. Small Moves: Beginning to Investigate Biogeochemical Exchange From the Seafloor to the Exterior of an Ice-Covered Ocean

    Science.gov (United States)

    German, C. R.; Boetius, A.

    2017-12-01

    We present results from two recent cruises, using the new Nereid Under Ice (NUI) vehicle aboard the FS Polarstern, in which we investigated biogeochemical fluxes from the deep seafloor of the Gakkel Ridge, an ultraslow spreading ridge that spans the ice-covered Arctic Ocean, and the mechanisms by which biogeochemical signals might be transferred from within the underlying ocean to the overlying Arctic ice. The scientific advances for this work progress hand in hand with technological capability. During a first cruise in 2014, our NUI-based investigations focused on photosynthetically-driven biogeochemical cycling in the uppermost water column and how to study such processes using in situ sensing immediately at and beneath the rough topography of the overlying ice-cover. For that work we relied entirely upon human-in-the-loop control of the vehicle via a single optical fiber light tether than provided real-time monitoring and control of the vehicle as it ranged laterally out under the ice up to 1km distant from the ship, conducting physical, geochemical and biological surveys. Instrumentation used for that work included multibeam mapping and imaging (digital still photographs and HD video), in situ spectroscopy to study light transmission through the ice and biogeochemical mapping of the ocean water column using a combination of CTD sensing, fluorometry and an in situ nitrate analyzer. Returning to the Arctic in 2016 we extended our exploration modes with NUI further, investigating for seafloor fluid flow at a shallow setting on the flanks of the Gakkel Ridge where the seabed rises from >4000m to movement of the ship (horizontal displacements of 1km or more) at the ice-covered ocean surface. While the existing NUI vehicle does not map directly to model payloads for future SLS missions to Europa or Enceladus it does provide for important small moves in the right direction.

  7. Robust Detection of Moving Human Target in Foliage-Penetration Environment Based on Hough Transform

    Directory of Open Access Journals (Sweden)

    P. Lei

    2014-04-01

    Full Text Available Attention has been focused on the robust moving human target detection in foliage-penetration environment, which presents a formidable task in a radar system because foliage is a rich scattering environment with complex multipath propagation and time-varying clutter. Generally, multiple-bounce returns and clutter are additionally superposed to direct-scatter echoes. They obscure true target echo and lead to poor visual quality time-range image, making target detection particular difficult. Consequently, an innovative approach is proposed to suppress clutter and mitigate multipath effects. In particular, a clutter suppression technique based on range alignment is firstly applied to suppress the time-varying clutter and the instable antenna coupling. Then entropy weighted coherent integration (EWCI algorithm is adopted to mitigate the multipath effects. In consequence, the proposed method effectively reduces the clutter and ghosting artifacts considerably. Based on the high visual quality image, the target trajectory is detected robustly and the radial velocity is estimated accurately with the Hough transform (HT. Real data used in the experimental results are provided to verify the proposed method.

  8. Infrared small target detection with kernel Fukunaga Koontz transform

    Science.gov (United States)

    Liu, Rui-ming; Liu, Er-qi; Yang, Jie; Zhang, Tian-hao; Wang, Fang-lin

    2007-09-01

    The Fukunaga-Koontz transform (FKT) has been proposed for many years. It can be used to solve two-pattern classification problems successfully. However, there are few researchers who have definitely extended FKT to kernel FKT (KFKT). In this paper, we first complete this task. Then a method based on KFKT is developed to detect infrared small targets. KFKT is a supervised learning algorithm. How to construct training sets is very important. For automatically detecting targets, the synthetic target images and real background images are used to train KFKT. Because KFKT can represent the higher order statistical properties of images, we expect better detection performance of KFKT than that of FKT. The well-devised experiments verify that KFKT outperforms FKT in detecting infrared small targets.

  9. Low, slow, small target recognition based on spatial vision network

    Science.gov (United States)

    Cheng, Zhao; Guo, Pei; Qi, Xin

    2018-03-01

    Traditional photoelectric monitoring is monitored using a large number of identical cameras. In order to ensure the full coverage of the monitoring area, this monitoring method uses more cameras, which leads to more monitoring and repetition areas, and higher costs, resulting in more waste. In order to reduce the monitoring cost and solve the difficult problem of finding, identifying and tracking a low altitude, slow speed and small target, this paper presents spatial vision network for low-slow-small targets recognition. Based on camera imaging principle and monitoring model, spatial vision network is modeled and optimized. Simulation experiment results demonstrate that the proposed method has good performance.

  10. Low Complexity Moving Target Parameter Estimation for MIMO Radar using 2D-FFT

    KAUST Repository

    Jardak, Seifallah

    2017-06-16

    In multiple-input multiple-output radar, to localize a target and estimate its reflection coefficient, a given cost function is usually optimized over a grid of points. The performance of such algorithms is directly affected by the grid resolution. Increasing the number of grid points enhances the resolution of the estimator but also increases its computational complexity exponentially. In this work, two reduced complexity algorithms are derived based on Capon and amplitude and phase estimation (APES) to estimate the reflection coefficient, angular location and, Doppler shift of multiple moving targets. By exploiting the structure of the terms, the cost-function is brought into a form that allows us to apply the two-dimensional fast-Fourier-transform (2D-FFT) and reduce the computational complexity of estimation. Using low resolution 2D-FFT, the proposed algorithm identifies sub-optimal estimates and feeds them as initial points to the derived Newton gradient algorithm. In contrast to the grid-based search algorithms, the proposed algorithm can optimally estimate on- and off-the-grid targets in very low computational complexity. A new APES cost-function with better estimation performance is also discussed. Generalized expressions of the Cramér-Rao lower bound are derived to asses the performance of the proposed algorithm.

  11. Modified linear predictive coding approach for moving target tracking by Doppler radar

    Science.gov (United States)

    Ding, Yipeng; Lin, Xiaoyi; Sun, Ke-Hui; Xu, Xue-Mei; Liu, Xi-Yao

    2016-07-01

    Doppler radar is a cost-effective tool for moving target tracking, which can support a large range of civilian and military applications. A modified linear predictive coding (LPC) approach is proposed to increase the target localization accuracy of the Doppler radar. Based on the time-frequency analysis of the received echo, the proposed approach first real-time estimates the noise statistical parameters and constructs an adaptive filter to intelligently suppress the noise interference. Then, a linear predictive model is applied to extend the available data, which can help improve the resolution of the target localization result. Compared with the traditional LPC method, which empirically decides the extension data length, the proposed approach develops an error array to evaluate the prediction accuracy and thus, adjust the optimum extension data length intelligently. Finally, the prediction error array is superimposed with the predictor output to correct the prediction error. A series of experiments are conducted to illustrate the validity and performance of the proposed techniques.

  12. Low Complexity Moving Target Parameter Estimation for MIMO Radar using 2D-FFT

    KAUST Repository

    Jardak, Seifallah; Ahmed, Sajid; Alouini, Mohamed-Slim

    2017-01-01

    In multiple-input multiple-output radar, to localize a target and estimate its reflection coefficient, a given cost function is usually optimized over a grid of points. The performance of such algorithms is directly affected by the grid resolution. Increasing the number of grid points enhances the resolution of the estimator but also increases its computational complexity exponentially. In this work, two reduced complexity algorithms are derived based on Capon and amplitude and phase estimation (APES) to estimate the reflection coefficient, angular location and, Doppler shift of multiple moving targets. By exploiting the structure of the terms, the cost-function is brought into a form that allows us to apply the two-dimensional fast-Fourier-transform (2D-FFT) and reduce the computational complexity of estimation. Using low resolution 2D-FFT, the proposed algorithm identifies sub-optimal estimates and feeds them as initial points to the derived Newton gradient algorithm. In contrast to the grid-based search algorithms, the proposed algorithm can optimally estimate on- and off-the-grid targets in very low computational complexity. A new APES cost-function with better estimation performance is also discussed. Generalized expressions of the Cramér-Rao lower bound are derived to asses the performance of the proposed algorithm.

  13. Attenuation correction for freely moving small animal brain PET studies based on a virtual scanner geometry

    International Nuclear Information System (INIS)

    Angelis, G I; Kyme, A Z; Ryder, W J; Fulton, R R; Meikle, S R

    2014-01-01

    Attenuation correction in positron emission tomography brain imaging of freely moving animals is a very challenging problem since the torso of the animal is often within the field of view and introduces a non negligible attenuating factor that can degrade the quantitative accuracy of the reconstructed images. In the context of unrestrained small animal imaging, estimation of the attenuation correction factors without the need for a transmission scan is highly desirable. An attractive approach that avoids the need for a transmission scan involves the generation of the hull of the animal’s head based on the reconstructed motion corrected emission images. However, this approach ignores the attenuation introduced by the animal’s torso. In this work, we propose a virtual scanner geometry which moves in synchrony with the animal’s head and discriminates between those events that traversed only the animal’s head (and therefore can be accurately compensated for attenuation) and those that might have also traversed the animal’s torso. For each recorded pose of the animal’s head a new virtual scanner geometry is defined and therefore a new system matrix must be calculated leading to a time-varying system matrix. This new approach was evaluated on phantom data acquired on the microPET Focus 220 scanner using a custom-made phantom and step-wise motion. Results showed that when the animal’s torso is within the FOV and not appropriately accounted for during attenuation correction it can lead to bias of up to 10% . Attenuation correction was more accurate when the virtual scanner was employed leading to improved quantitative estimates (bias < 2%), without the need to account for the attenuation introduced by the extraneous compartment. Although the proposed method requires increased computational resources, it can provide a reliable approach towards quantitatively accurate attenuation correction for freely moving animal studies. (paper)

  14. Performance limits for exo-clutter Ground Moving Target Indicator (GMTI) radar.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2010-09-01

    The performance of a Ground Moving Target Indicator (GMTI) radar system depends on a variety of factors, many which are interdependent in some manner. It is often difficult to 'get your arms around' the problem of ascertaining achievable performance limits, and yet those limits exist and are dictated by physics. This report identifies and explores those limits, and how they depend on hardware system parameters and environmental conditions. Ultimately, this leads to a characterization of parameters that offer optimum performance for the overall GMTI radar system. While the information herein is not new to the literature, its collection into a single report hopes to offer some value in reducing the 'seek time'.

  15. Reduced complexity FFT-based DOA and DOD estimation for moving target in bistatic MIMO radar

    KAUST Repository

    Ali, Hussain

    2016-06-24

    In this paper, we consider a bistatic multiple-input multiple-output (MIMO) radar. We propose a reduced complexity algorithm to estimate the direction-of-arrival (DOA) and direction-of-departure (DOD) for moving target. We show that the calculation of parameter estimation can be expressed in terms of one-dimensional fast-Fourier-transforms which drastically reduces the complexity of the optimization algorithm. The performance of the proposed algorithm is compared with the two-dimension multiple signal classification (2D-MUSIC) and reduced-dimension MUSIC (RD-MUSIC) algorithms. It is shown by simulations, our proposed algorithm has better estimation performance and lower computational complexity compared to the 2D-MUSIC and RD-MUSIC algorithms. Moreover, simulation results also show that the proposed algorithm achieves the Cramer-Rao lower bound. © 2016 IEEE.

  16. TargetRNA: a tool for predicting targets of small RNA action in bacteria

    OpenAIRE

    Tjaden, Brian

    2008-01-01

    Many small RNA (sRNA) genes in bacteria act as posttranscriptional regulators of target messenger RNAs. Here, we present TargetRNA, a web tool for predicting mRNA targets of sRNA action in bacteria. TargetRNA takes as input a genomic sequence that may correspond to an sRNA gene. TargetRNA then uses a dynamic programming algorithm to search each annotated message in a specified genome for mRNAs that evince basepair-binding potential to the input sRNA sequence. Based on the calculated basepair-...

  17. Global analysis of small molecule binding to related protein targets.

    Directory of Open Access Journals (Sweden)

    Felix A Kruger

    2012-01-01

    Full Text Available We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity.

  18. Urea transporter proteins as targets for small-molecule diuretics.

    Science.gov (United States)

    Esteva-Font, Cristina; Anderson, Marc O; Verkman, Alan S

    2015-02-01

    Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.

  19. A Novel Detection Method for Underwater Moving Targets by Measuring Their ELF Emissions with Inductive Sensors

    Directory of Open Access Journals (Sweden)

    Jinhong Wang

    2017-07-01

    Full Text Available In this article, we propose a novel detection method for underwater moving targets by detecting their extremely low frequency (ELF emissions with inductive sensors. The ELF field source of the targets is modeled by a horizontal electric dipole at distances more than several times of the targets’ length. The formulas for the fields produced in air are derived with a three-layer model (air, seawater and seafloor and are evaluated with a complementary numerical integration technique. A proof of concept measurement is presented. The ELF emissions from a surface ship were detected by inductive electronic and magnetic sensors as the ship was leaving a harbor. ELF signals are of substantial strength and have typical characteristic of harmonic line spectrum, and the fundamental frequency has a direct relationship with the ship’s speed. Due to the high sensitivity and low noise level of our sensors, it is capable of resolving weak ELF signals at long distance. In our experiment, a detection distance of 1300 m from the surface ship above the sea surface was realized, which shows that this method would be an appealing complement to the usual acoustic detection and magnetic anomaly detection capability.

  20. Tumor trailing strategy for intensity-modulated radiation therapy of moving targets

    International Nuclear Information System (INIS)

    Trofimov, Alexei; Vrancic, Christian; Chan, Timothy C. Y.; Sharp, Gregory C.; Bortfeld, Thomas

    2008-01-01

    Internal organ motion during the course of radiation therapy of cancer affects the distribution of the delivered dose and, generally, reduces its conformality to the targeted volume. Previously proposed approaches aimed at mitigating the effect of internal motion in intensity-modulated radiation therapy (IMRT) included expansion of the target margins, motion-correlated delivery (e.g., respiratory gating, tumor tracking), and adaptive treatment plan optimization employing a probabilistic description of motion. We describe and test the tumor trailing strategy, which utilizes the synergy of motion-adaptive treatment planning and delivery methods. We regard the (rigid) target motion as a superposition of a relatively fast cyclic component (e.g., respiratory) and slow aperiodic trends (e.g., the drift of exhalation baseline). In the trailing approach, these two components of motion are decoupled and dealt with separately. Real-time motion monitoring is employed to identify the 'slow' shifts, which are then corrected by applying setup adjustments. The delivery does not track the target position exactly, but trails the systematic trend due to the delay between the time a shift occurs, is reliably detected, and, subsequently, corrected. The ''fast'' cyclic motion is accounted for with a robust motion-adaptive treatment planning, which allows for variability in motion parameters (e.g., mean and extrema of the tidal volume, variable period of respiration, and expiratory duration). Motion-surrogate data from gated IMRT treatments were used to provide probability distribution data for motion-adaptive planning and to test algorithms that identified systematic trends in the character of motion. Sample IMRT fields were delivered on a clinical linear accelerator to a programmable moving phantom. Dose measurements were performed with a commercial two-dimensional ion-chamber array. The results indicate that by reducing intrafractional motion variability, the trailing strategy

  1. Program-target methods of management small business

    Directory of Open Access Journals (Sweden)

    Gurova Ekaterina

    2017-01-01

    Full Text Available Experience of small businesses in Russia are just beginning their path to development. difficulties arise with the involvement of small businesses in the implementation of government development programmes. Small business in modern conditions to secure a visible prospect of development without the implementation of state support programmes. Ways and methods of regulation of development of the market economy are diverse. The total mass of the huge role is played by the program-target methods of regulation. The article describes the basic principles on the use of program-target approach to the development of a specific sector of the economy, as small businesses, designed to play an important role in getting the national economy out of crisis. The material in this publication is built from the need to maintain the connection between the theory of government regulation, practice of formation of development programs at the regional level and the needs of small businesses. Essential for the formation of entrepreneurship development programmes is to preserve the flexibility of small businesses in making management decisions related to the selection and change of activities.

  2. Mismatched summation mechanisms in older adults for the perception of small moving stimuli.

    Science.gov (United States)

    McDougall, Thomas J; Nguyen, Bao N; McKendrick, Allison M; Badcock, David R

    2018-01-01

    Previous studies have found evidence for reduced cortical inhibition in aging visual cortex. Reduced inhibition could plausibly increase the spatial area of excitation in receptive fields of older observers, as weaker inhibitory processes would allow the excitatory receptive field to dominate and be psychophysically measureable over larger areas. Here, we investigated aging effects on spatial summation of motion direction using the Battenberg summation method, which aims to control the influence of locally generated internal noise changes by holding overall display size constant. This method produces more accurate estimates of summation area than conventional methods that simply increase overall stimulus dimensions. Battenberg stimuli have a checkerboard arrangement, where check size (luminance-modulated drifting gratings alternating with mean luminance areas), but not display size, is varied and compared with performance for a full field stimulus to provide a measure of summation. Motion direction discrimination thresholds, where contrast was the dependent variable, were measured in 14 younger (24-34 years) and 14 older (62-76 years) adults. Older observers were less sensitive for all check sizes, but the relative sensitivity across sizes, also differed between groups. In the older adults, the full field stimulus offered smaller performance improvements compared to that for younger adults, specifically for the small checked Battenberg stimuli. This suggests aging impacts on short-range summation mechanisms, potentially underpinned by larger summation areas for the perception of small moving stimuli. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Learning the trajectory of a moving visual target and evolution of its tracking in the monkey

    Science.gov (United States)

    Bourrelly, Clara; Quinet, Julie; Cavanagh, Patrick

    2016-01-01

    An object moving in the visual field triggers a saccade that brings its image onto the fovea. It is followed by a combination of slow eye movements and catch-up saccades that try to keep the target image on the fovea as long as possible. The accuracy of this ability to track the “here-and-now” location of a visual target contrasts with the spatiotemporally distributed nature of its encoding in the brain. We show in six experimentally naive monkeys how this performance is acquired and gradually evolves during successive daily sessions. During the early exposure, the tracking is mostly saltatory, made of relatively large saccades separated by low eye velocity episodes, demonstrating that accurate (here and now) pursuit is not spontaneous and that gaze direction lags behind its location most of the time. Over the sessions, while the pursuit velocity is enhanced, the gaze is more frequently directed toward the current target location as a consequence of a 25% reduction in the number of catch-up saccades and a 37% reduction in size (for the first saccade). This smoothing is observed at several scales: during the course of single trials, across the set of trials within a session, and over successive sessions. We explain the neurophysiological processes responsible for this combined evolution of saccades and pursuit in the absence of stringent training constraints. More generally, our study shows that the oculomotor system can be used to discover the neural mechanisms underlying the ability to synchronize a motor effector with a dynamic external event. PMID:27683886

  4. Monetary policy and inflation targeting in a small open-economy

    OpenAIRE

    Abdul Karim, Zulkefly; Md. Said, Fathin Faezah; Jusoh, Mansor; Md. Thahir, Md. Zyadi

    2009-01-01

    This paper investigates the transmission mechanism of monetary policy and inflation targeting in a small open-economy by using backward-looking of aggregate supply (AS) and aggregate demand (AD) framework. Since September 1998 until July 2005, Malaysia has implemented a currency pegged to the U.S dollar in responding to the Asian financial crisis. However, since the 21st of July 2005 until at present, the Central Bank of Malaysia (CBM) has eliminated pegging with the U.S dollar and moved to t...

  5. Targeting p53 by small molecules in hematological malignancies

    OpenAIRE

    Saha, Manujendra N; Qiu, Lugui; Chang, Hong

    2013-01-01

    p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their ant...

  6. The registration of non-cooperative moving targets laser point cloud in different view point

    Science.gov (United States)

    Wang, Shuai; Sun, Huayan; Guo, Huichao

    2018-01-01

    Non-cooperative moving target multi-view cloud registration is the key technology of 3D reconstruction of laser threedimension imaging. The main problem is that the density changes greatly and noise exists under different acquisition conditions of point cloud. In this paper, firstly, the feature descriptor is used to find the most similar point cloud, and then based on the registration algorithm of region segmentation, the geometric structure of the point is extracted by the geometric similarity between point and point, The point cloud is divided into regions based on spectral clustering, feature descriptors are created for each region, searching to find the most similar regions in the most similar point of view cloud, and then aligning the pair of point clouds by aligning their minimum bounding boxes. Repeat the above steps again until registration of all point clouds is completed. Experiments show that this method is insensitive to the density of point clouds and performs well on the noise of laser three-dimension imaging.

  7. Small molecule screening identifies targetable zebrafish pigmentation pathways

    DEFF Research Database (Denmark)

    Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D

    2012-01-01

    Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...... and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types...

  8. An indirect adaptive neural control of a visual-based quadrotor robot for pursuing a moving target.

    Science.gov (United States)

    Shirzadeh, Masoud; Amirkhani, Abdollah; Jalali, Aliakbar; Mosavi, Mohammad R

    2015-11-01

    This paper aims to use a visual-based control mechanism to control a quadrotor type aerial robot which is in pursuit of a moving target. The nonlinear nature of a quadrotor, on the one hand, and the difficulty of obtaining an exact model for it, on the other hand, constitute two serious challenges in designing a controller for this UAV. A potential solution for such problems is the use of intelligent control methods such as those that rely on artificial neural networks and other similar approaches. In addition to the two mentioned problems, another problem that emerges due to the moving nature of a target is the uncertainty that exists in the target image. By employing an artificial neural network with a Radial Basis Function (RBF) an indirect adaptive neural controller has been designed for a quadrotor robot in search of a moving target. The results of the simulation for different paths show that the quadrotor has efficiently tracked the moving target. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  9. Piezoelectric translator. A simple and inexpensive device to move microelectrodes and micropipettes small distances rapidly.

    Science.gov (United States)

    Lederer, W J

    1983-09-01

    A device is described that is capable of rapidly moving microelectrodes and micropipettes over distances up to 15 mu. This piezoelectric transLator uses the diaphragm from virtually any available piezoelectric buzzer in combination with simple physical support and drive electronics. All of the necessary details for the construction of this small device are presented. Each finished unit is about 2 cm long with a diameter of 2 cm and can be readily adapted to existing manipulators. The translator has been found useful in aiding the independent penetration by one or more microelectrodes of single cells or of more complicated multicellular preparations (including those that lie behind a connective tissue layer). This new device offers fine control of microelectrode motion that cannot be obtained by the other methods used to aid microelectrode and micropipette penetration of cell membranes (e.g. capacitance overcompensation--"ringing in"' or "tickling"--or tapping the manipulator base). Finally, the device described in this paper is extremely simple and inexpensive to build.

  10. Small Intracranial Aneurysm Treatment Using Target (®) Ultrasoft (™) Coils.

    Science.gov (United States)

    Jindal, Gaurav; Miller, Timothy; Iyohe, Moronke; Shivashankar, Ravi; Prasad, Vikram; Gandhi, Dheeraj

    2016-06-01

    The introduction of small, soft, complex-shaped microcoils has helped facilitate the endovascular treatment of small intracranial aneurysms (IAs) over the last several years. Here, we evaluate the initial safety and efficacy of treating small IAs using only Target(®) Ultrasoft(™) coils. A retrospective review of a prospectively maintained clinical database at a single, high volume, teaching hospital was performed from September 2011 to May 2015. IAs smaller than or equal to 5.0 mm in maximal dimension treated with only Target(®) Ultrasoft(™) coils were included. A total of 50 patients with 50 intracranial aneurysms were included. Subarachnoid hemorrhage from index aneurysm rupture was the indication for treatment in 23 of 50 (46%) cases, and prior subarachnoid hemorrhage (SAH) from another aneurysm was the indication for treatment in eight of 50 (16%) cases. The complete aneurysm occlusion rate was 70% (35/50), the minimal residual aneurysm rate was 14% (7/50), and residual aneurysm rate was 16% (8/50). One intraoperative aneurysm rupture occurred. Three patients died during hospitalization from clinical sequelae of subarachnoid hemorrhage. Follow-up at a mean of 13.6 months demonstrated complete aneurysm occlusion in 75% (30/40) of cases, near complete occlusion in 15% (6/40) of cases, and residual aneurysm in 10% (4/40) of cases, all four of which were retreated. Our initial results using only Target(®) Ultrasoft(™) coils for the endovascular treatment of small intracranial aneurysms demonstrate initial excellent safety and efficacy profiles.

  11. 3D range-gated super-resolution imaging based on stereo matching for moving platforms and targets

    Science.gov (United States)

    Sun, Liang; Wang, Xinwei; Zhou, Yan

    2017-11-01

    3D range-gated superresolution imaging is a novel 3D reconstruction technique for target detection and recognition with good real-time performance. However, for moving targets or platforms such as airborne, shipborne, remote operated vehicle and autonomous vehicle, 3D reconstruction has a large error or failure. In order to overcome this drawback, we propose a method of stereo matching for 3D range-gated superresolution reconstruction algorithm. In experiment, the target is a doll of Mario with a height of 38cm at the location of 34m, and we obtain two successive frame images of the Mario. To confirm our method is effective, we transform the original images with translation, rotation, scale and perspective, respectively. The experimental result shows that our method has a good result of 3D reconstruction for moving targets or platforms.

  12. An Adaptive Moving Target Imaging Method for Bistatic Forward-Looking SAR Using Keystone Transform and Optimization NLCS.

    Science.gov (United States)

    Li, Zhongyu; Wu, Junjie; Huang, Yulin; Yang, Haiguang; Yang, Jianyu

    2017-01-23

    Bistatic forward-looking SAR (BFSAR) is a kind of bistatic synthetic aperture radar (SAR) system that can image forward-looking terrain in the flight direction of an aircraft. Until now, BFSAR imaging theories and methods for a stationary scene have been researched thoroughly. However, for moving-target imaging with BFSAR, the non-cooperative movement of the moving target induces some new issues: (I) large and unknown range cell migration (RCM) (including range walk and high-order RCM); (II) the spatial-variances of the Doppler parameters (including the Doppler centroid and high-order Doppler) are not only unknown, but also nonlinear for different point-scatterers. In this paper, we put forward an adaptive moving-target imaging method for BFSAR. First, the large and unknown range walk is corrected by applying keystone transform over the whole received echo, and then, the relationships among the unknown high-order RCM, the nonlinear spatial-variances of the Doppler parameters, and the speed of the mover, are established. After that, using an optimization nonlinear chirp scaling (NLCS) technique, not only can the unknown high-order RCM be accurately corrected, but also the nonlinear spatial-variances of the Doppler parameters can be balanced. At last, a high-order polynomial filter is applied to compress the whole azimuth data of the moving target. Numerical simulations verify the effectiveness of the proposed method.

  13. An Adaptive Moving Target Imaging Method for Bistatic Forward-Looking SAR Using Keystone Transform and Optimization NLCS

    Directory of Open Access Journals (Sweden)

    Zhongyu Li

    2017-01-01

    Full Text Available Bistatic forward-looking SAR (BFSAR is a kind of bistatic synthetic aperture radar (SAR system that can image forward-looking terrain in the flight direction of an aircraft. Until now, BFSAR imaging theories and methods for a stationary scene have been researched thoroughly. However, for moving-target imaging with BFSAR, the non-cooperative movement of the moving target induces some new issues: (I large and unknown range cell migration (RCM (including range walk and high-order RCM; (II the spatial-variances of the Doppler parameters (including the Doppler centroid and high-order Doppler are not only unknown, but also nonlinear for different point-scatterers. In this paper, we put forward an adaptive moving-target imaging method for BFSAR. First, the large and unknown range walk is corrected by applying keystone transform over the whole received echo, and then, the relationships among the unknown high-order RCM, the nonlinear spatial-variances of the Doppler parameters, and the speed of the mover, are established. After that, using an optimization nonlinear chirp scaling (NLCS technique, not only can the unknown high-order RCM be accurately corrected, but also the nonlinear spatial-variances of the Doppler parameters can be balanced. At last, a high-order polynomial filter is applied to compress the whole azimuth data of the moving target. Numerical simulations verify the effectiveness of the proposed method.

  14. An optimisation algorithm for determination of treatment margins around moving and deformable targets

    International Nuclear Information System (INIS)

    Redpath, Anthony Thomas; Muren, Ludvig Paul

    2005-01-01

    Purpose: Determining treatment margins for inter-fractional motion of moving and deformable clinical target volumes (CTVs) remains a major challenge. This paper describes and applies an optimisation algorithm designed to derive such margins. Material and methods: The algorithm works by expanding the CTV, as determined from a pre-treatment or planning scan, to enclose the CTV positions observed during treatment. CTV positions during treatment may be obtained using, for example, repeat CT scanning and/or repeat electronic portal imaging (EPI). The algorithm can be applied to both individual patients and to a set of patients. The margins derived will minimise the excess volume outside the envelope that encloses all observed CTV positions (the CTV envelope). Initially, margins are set such that the envelope is more than adequately covered when the planning CTV is expanded. The algorithm uses an iterative method where the margins are sampled randomly and are then either increased or decreased randomly. The algorithm is tested on a set of 19 bladder cancer patients that underwent weekly repeat CT scanning and EPI throughout their treatment course. Results: From repeated runs on individual patients, the algorithm produces margins within a range of ±2 mm that lie among the best results found with an exhaustive search approach, and that agree within 3 mm with margins determined by a manual approach on the same data. The algorithm could be used to determine margins to cover any specified geometrical uncertainty, and allows for the determination of reduced margins by relaxing the coverage criteria, for example disregarding extreme CTV positions, or an arbitrarily selected volume fraction of the CTV envelope, and/or patients with extreme geometrical uncertainties. Conclusion: An optimisation approach to margin determination is found to give reproducible results within the accuracy required. The major advantage with this algorithm is that it is completely empirical, and it is

  15. Margin estimation and disturbances of irradiation field in layer-stacking carbon-ion beams for respiratory moving targets.

    Science.gov (United States)

    Tajiri, Shinya; Tashiro, Mutsumi; Mizukami, Tomohiro; Tsukishima, Chihiro; Torikoshi, Masami; Kanai, Tatsuaki

    2017-11-01

    Carbon-ion therapy by layer-stacking irradiation for static targets has been practised in clinical treatments. In order to apply this technique to a moving target, disturbances of carbon-ion dose distributions due to respiratory motion have been studied based on the measurement using a respiratory motion phantom, and the margin estimation given by the square root of the summation Internal margin2+Setup margin2 has been assessed. We assessed the volume in which the variation in the ratio of the dose for a target moving due to respiration relative to the dose for a static target was within 5%. The margins were insufficient for use with layer-stacking irradiation of a moving target, and an additional margin was required. The lateral movement of a target converts to the range variation, as the thickness of the range compensator changes with the movement of the target. Although the additional margin changes according to the shape of the ridge filter, dose uniformity of 5% can be achieved for a spherical target 93 mm in diameter when the upward range variation is limited to 5 mm and the additional margin of 2.5 mm is applied in case of our ridge filter. Dose uniformity in a clinical target largely depends on the shape of the mini-peak as well as on the bolus shape. We have shown the relationship between range variation and dose uniformity. In actual therapy, the upper limit of target movement should be considered by assessing the bolus shape. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  16. Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jai-Woong; Sawant, Amit; Suh, Yelin; Cho, Byung-Chul; Suh, Tae-Suk; Keall, Paul [Department of Biomedical Engineering, College of Medicine, Catholic University of Korea, Seoul, Korea 131-700 and Research Institute of Biomedical Engineering, Catholic University of Korea, Seoul, 131-700 (Korea, Republic of); Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States); Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States) and Department of Radiation Oncology, Asan Medical Center, Seoul, 138-736 (Korea, Republic of); Department of Biomedical Engineering, College of Medicine, Catholic University of Korea, Seoul, 131-700 and Research Institute of Biomedical Engineering, Catholic University of Korea, Seoul, 131-700 (Korea, Republic of); Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States) and Radiation Physics Laboratory, Sydney Medical School, University of Sydney, 2006 (Australia)

    2011-07-15

    Purpose: In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. Methods: The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a {gamma}-test with a 3%/3 mm criterion. Results: The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the {gamma}-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation

  17. Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

    Science.gov (United States)

    Yoon, Jai-Woong; Sawant, Amit; Suh, Yelin; Cho, Byung-Chul; Suh, Tae-Suk; Keall, Paul

    2011-07-01

    In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. The delivery efficiency of

  18. On small things in water moving around: Purcell's contributions to biology

    Science.gov (United States)

    Berg, Howard

    2012-02-01

    I went to see Purcell after finishing my course work for the Ph.D. (1961) to ask whether I might join his group. ``But I don't have any graduate students,`` he said. ``Why is that?'' I asked. ``I can't think of anything to do,'' he replied. That was a wipe out. After I had finished my Ph.D. with Ramsey on the hydrogen maser (1964), Ed and I came up with an idea that led to work on sedimentation field-flow fractionation (PNAS 1967). We had hoped this method would be useful for biology, but problems of adsorption of proteins to surfaces stood in the way. Then I moved over to the biology department and got interested in the motile behavior of bacteria (1968). Here was a subject that I thought Ed would really enjoy. There were wonderful movies made by Norbert Pfennig of experiments done by Theodor Engelmann in the 1880's. We found a 16-mm projector and looked at these movies on Ed's office wall. Ed's first comment proved seminal, ''How can such a small cell swim in a straight line?'' We thought about how cells count molecules in their environment and wrote ``Physics of chemoreception,'' (Biophys. J.,1977). In the meantime, Ed gave a memorable lecture at Viki Weisskopf's retirement symposium, his classic ``Life at low Reynolds number'' (Am. J. Phys. 1977). Ed really wanted to understand what it would be like to swim like a bacterium! He wasn't very interested in what the literature had to say about such a problem, he wanted to think it through for himself. My role was straight man. I very much enjoyed the ride.

  19. Implementation of a Worksite Wellness Program Targeting Small Businesses

    Science.gov (United States)

    Stinson, Kaylan E.; Metcalf, Dianne; Fang, Hai; Brockbank, Claire vS.; Jinnett, Kimberly; Reynolds, Stephen; Trotter, Margo; Witter, Roxana; Tenney, Liliana; Atherly, Adam; Goetzel, Ron Z.

    2015-01-01

    Objective: To assess small business adoption and need for a worksite wellness program in a longitudinal study of health risks, productivity, workers' compensation rates, and claims costs. Methods: Health risk assessment data from 6507 employees in 260 companies were examined. Employer and employee data are reported as frequencies, with means and standard deviations reported when applicable. Results: Of the 260 companies enrolled in the health risk management program, 71% continued more than 1 year, with 97% reporting that worker wellness improves worker safety. Of 6507 participating employees, 34.3% were overweight and 25.6% obese. Approximately one in five participants reported depression. Potentially modifiable conditions affecting 15% or more of enrollees include chronic fatigue, sleeping problems, headaches, arthritis, hypercholesterolemia, and hypertension. Conclusions: Small businesses are a suitable target for the introduction of health promotion programs. PMID:25563536

  20. Damage phenomena at target surface by small leak

    International Nuclear Information System (INIS)

    Jeong, Kyung Chai; Jeong, J. Y.; Kim, B. H.; Kim, T. J.; Choi, J. H.

    2001-04-01

    Design of the steam generator should be considered the safety about the sodium-water reaction occurred by water leak in heat transfer tube. Water leak mainly occurred from welding defect at the process of tube connection, the vibration of heat transfer tube bundle in steam generating system, fretting, and pin hole in original tube manufacturing. The classification of water leak divided to two parts, roughly, in case of the water leak studies. One is small leak phenomena analysis, and the other is it of large leak which was mainly treated to the evaluation on pressure increasing from hydrogen gas formed by sodium-water reaction in sodium system. In small water leak, the leak propagation phenomena and the development of leak detecting system at initial stage of small water leak were studied, mainly. In this study, the corrosion phenomena on the target tube surface appeared by sodium-water reaction was analyzed through the small water leak experiments, and, also, the jet phenomena formed by N 2 gas injection through the leak nozzle under water medium was observed

  1. New small molecules targeting apoptosis and cell viability in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Doris Maugg

    Full Text Available Despite the option of multimodal therapy in the treatment strategies of osteosarcoma (OS, the most common primary malignant bone tumor, the standard therapy has not changed over the last decades and still involves multidrug chemotherapy and radical surgery. Although successfully applied in many patients a large number of patients eventually develop recurrent or metastatic disease in which current therapeutic regimens often lack efficacy. Thus, new therapeutic strategies are urgently needed. In this study, we performed a phenotypic high-throughput screening campaign using a 25,000 small-molecule diversity library to identify new small molecules selectively targeting osteosarcoma cells. We could identify two new small molecules that specifically reduced cell viability in OS cell lines U2OS and HOS, but affected neither hepatocellular carcinoma cell line (HepG2 nor primary human osteoblasts (hOB. In addition, the two compounds induced caspase 3 and 7 activity in the U2OS cell line. Compared to conventional drugs generally used in OS treatment such as doxorubicin, we indeed observed a greater sensitivity of OS cell viability to the newly identified compounds compared to doxorubicin and staurosporine. The p53-negative OS cell line Saos-2 almost completely lacked sensitivity to compound treatment that could indicate a role of p53 in the drug response. Taken together, our data show potential implications for designing more efficient therapies in OS.

  2. Hic-Et-Nunc (Here-and-Now Encoding of a Moving Target for its Saccadic Foveation

    Directory of Open Access Journals (Sweden)

    Laurent Goffart

    2012-10-01

    Full Text Available The neural representation of a moving target undergoes a spatiotemporal “diffusion” while the associated retinal activity propagates toward the motor centers and recruits the appropriate muscles for its interception in the external world. Indeed, the divergent projections within the visual system and the transmissions of signals through multiple relays, with diverse conduction velocities and integration times, lead to activities that are spatially and temporally distributed across several brain regions. In spite of this neural “blurring”, accurate saccadic eye movements can be made to bring the image of a moving target onto the fovea. Such a performance indicates that the brain is able to rapidly estimate the current spatiotemporal coordinates of the target, at least at the time of saccade landing. We tested in the monkey the robustness of this estimate when a change in eye position and a delay are experimentally added before the animal launches a saccade toward a moving target and in the absence of visual feedback. These spatiotemporal perturbations were induced by a brief microstimulation in the deep superior colliculus. The results show that the interceptive saccades can remain accurate and relatively independent of the time taken to react and to foveate the target. We propose that the brain builds an estimate of the expected and current spatiotemporal (hic-et-nunc coordinates of the target and that this signal feeds the same local feedback loop as the mechanism proposed for guiding saccades toward a stationary target (Fleuriet and Goffart, 2012 Journal of Neuroscience 32 452–461.

  3. Targeting small airways in asthma: Improvement in clinical benefit?

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

    Background and Aim:  Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions:  Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

  4. Targeting small airways in asthma: Improvement in clinical benefit?

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2010-01-01

    Background and Aim: Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy. This review will focus on the importance and potential clinical benefit of targeting the lung...... half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference...... with regard to conventional clinical indices of lung function and asthma control. Conclusions: Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether...

  5. Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

    Science.gov (United States)

    Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

    2014-01-01

    Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

  6. Study on the Detection of Moving Target in the Mining Method Based on Hybrid Algorithm for Sports Video Analysis

    Directory of Open Access Journals (Sweden)

    Huang Tian

    2014-10-01

    Full Text Available Moving object detection and tracking is the computer vision and image processing is a hot research direction, based on the analysis of the moving target detection and tracking algorithm in common use, focus on the sports video target tracking non rigid body. In sports video, non rigid athletes often have physical deformation in the process of movement, and may be associated with the occurrence of moving target under cover. Media data is surging to fast search and query causes more difficulties in data. However, the majority of users want to be able to quickly from the multimedia data to extract the interested content and implicit knowledge (concepts, rules, rules, models and correlation, retrieval and query quickly to take advantage of them, but also can provide the decision support problem solving hierarchy. Based on the motion in sport video object as the object of study, conducts the system research from the theoretical level and technical framework and so on, from the layer by layer mining between low level motion features to high-level semantic motion video, not only provides support for users to find information quickly, but also can provide decision support for the user to solve the problem.

  7. Make your small practice thrive. Physicians moving from big practices to small must know the business side of medicine.

    Science.gov (United States)

    Cowan, D

    2001-01-01

    Trying to gain a measure of control over their working lives, some physicians are abandoning large group practices for smaller groups. Large groups enjoy whole teams of people performing vital business tasks. Small practices rely on one or two key physicians and managers to tackle everything from customer service to marketing, medical records to human resources. Learn valuable tips for thriving in a small environment and using that extra control to achieve job satisfaction.

  8. Opportune acquisition and tracking time for the fast-moving targets in a ground-based telescope

    Science.gov (United States)

    Chen, Juan; Wang, Jianli; Chen, Tao

    2004-10-01

    Acquisition is defined as identification for a fixed target in the related field of sight (FOS), while tracking means the sway of the telescope's axis of sight (AOS). The automatic acquisition and tracking is a process in which the operating way of the telescope should be switched from guiding to automatic tracking. There are some kinds of method to improve the acquisition and tracking ability for fast moving targets: to extend the acquisition and tracking FOS with memory and storage information of the sensor system; the multimode control to improve the dynamic property of the servo system; to choose an opportune time for acquisition and tracking; to select the control regulator parameter in every working states. If the processor of the CCD sensor can temporarily remember and save the information of the target before it moves out of the FOS, correspondingly, the FOS may be extended. The data forecast technology is used to store the target information. The automatic interception experiments are carried out to verify the control strategy.

  9. Bispecific small molecule-antibody conjugate targeting prostate cancer.

    Science.gov (United States)

    Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

    2013-10-29

    Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

  10. Bispecific small molecule–antibody conjugate targeting prostate cancer

    Science.gov (United States)

    Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

    2013-01-01

    Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

  11. Moving-Target Position Estimation Using GPU-Based Particle Filter for IoT Sensing Applications

    Directory of Open Access Journals (Sweden)

    Seongseop Kim

    2017-11-01

    Full Text Available A particle filter (PF has been introduced for effective position estimation of moving targets for non-Gaussian and nonlinear systems. The time difference of arrival (TDOA method using acoustic sensor array has normally been used to for estimation by concealing the location of a moving target, especially underwater. In this paper, we propose a GPU -based acceleration of target position estimation using a PF and propose an efficient system and software architecture. The proposed graphic processing unit (GPU-based algorithm has more advantages in applying PF signal processing to a target system, which consists of large-scale Internet of Things (IoT-driven sensors because of the parallelization which is scalable. For the TDOA measurement from the acoustic sensor array, we use the generalized cross correlation phase transform (GCC-PHAT method to obtain the correlation coefficient of the signal using Fast Fourier Transform (FFT, and we try to accelerate the calculations of GCC-PHAT based TDOA measurements using FFT with GPU compute unified device architecture (CUDA. The proposed approach utilizes a parallelization method in the target position estimation algorithm using GPU-based PF processing. In addition, it could efficiently estimate sudden movement change of the target using GPU-based parallel computing which also can be used for multiple target tracking. It also provides scalability in extending the detection algorithm according to the increase of the number of sensors. Therefore, the proposed architecture can be applied in IoT sensing applications with a large number of sensors. The target estimation algorithm was verified using MATLAB and implemented using GPU CUDA. We implemented the proposed signal processing acceleration system using target GPU to analyze in terms of execution time. The execution time of the algorithm is reduced by 55% from to the CPU standalone operation in target embedded board, NVIDIA Jetson TX1. Also, to apply large

  12. Efficient moving target analysis for inverse synthetic aperture radar images via joint speeded-up robust features and regular moment

    Science.gov (United States)

    Yang, Hongxin; Su, Fulin

    2018-01-01

    We propose a moving target analysis algorithm using speeded-up robust features (SURF) and regular moment in inverse synthetic aperture radar (ISAR) image sequences. In our study, we first extract interest points from ISAR image sequences by SURF. Different from traditional feature point extraction methods, SURF-based feature points are invariant to scattering intensity, target rotation, and image size. Then, we employ a bilateral feature registering model to match these feature points. The feature registering scheme can not only search the isotropic feature points to link the image sequences but also reduce the error matching pairs. After that, the target centroid is detected by regular moment. Consequently, a cost function based on correlation coefficient is adopted to analyze the motion information. Experimental results based on simulated and real data validate the effectiveness and practicability of the proposed method.

  13. Leveraging a Community Participatory Framework to Move Climate Survey Data into Action at a Small College

    Science.gov (United States)

    Peters, C. Ellen; Benitez, Michael, Jr.

    2017-01-01

    A participatory framework in conducting research and implementing decisions can engage multiple constituents throughout a college community. At a small college, it is especially relevant, because nonmajority groups are especially vulnerable because of a smaller critical mass.

  14. Systematic analysis of neutron yields from thick targets bombarded by heavy ions and protons with moving source model

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Takashi; Kurosawa, Tadahiro; Nakamura, Takashi E-mail: nakamura@cyric.tohoku.ac.jp

    2002-03-21

    A simple phenomenological analysis using the moving source model has been performed on the neutron energy spectra produced by bombarding thick targets with high energy heavy ions which have been systematically measured at the Heavy-Ion Medical Accelerator (HIMAC) facility (located in Chiba, Japan) of the National Institute of Radiological Sciences (NIRS). For the bombardment of both heavy ions and protons in the energy region of 100-500 MeV per nucleon, the moving source model incorporating the knock-on process could be generally successful in reproducing the measured neutron spectra within a factor of two margin of accuracy. This phenomenological analytical equation is expressed having several parameters as functions of atomic number Z{sub p}, mass number A{sub p}, energy per nucleon E{sub p} for projectile, and atomic number Z{sub T}, mass number A{sub T} for target. By inputting these basic data for projectile and target into this equation we can easily estimate the secondary neutron energy spectra at an emission angle of 0-90 deg. for bombardment with heavy ions and protons in the aforementioned energy region. This method will be quite useful to estimate the neutron source term in the neutron shielding design of high energy proton and heavy ion accelerators.

  15. Search efficiency of biased migration towards stationary or moving targets in heterogeneously structured environments

    Science.gov (United States)

    Azimzade, Youness; Mashaghi, Alireza

    2017-12-01

    Efficient search acts as a strong selective force in biological systems ranging from cellular populations to predator-prey systems. The search processes commonly involve finding a stationary or mobile target within a heterogeneously structured environment where obstacles limit migration. An open generic question is whether random or directionally biased motions or a combination of both provide an optimal search efficiency and how that depends on the motility and density of targets and obstacles. To address this question, we develop a simple model that involves a random walker searching for its targets in a heterogeneous medium of bond percolation square lattice and used mean first passage time (〈T 〉 ) as an indication of average search time. Our analysis reveals a dual effect of directional bias on the minimum value of 〈T 〉 . For a homogeneous medium, directionality always decreases 〈T 〉 and a pure directional migration (a ballistic motion) serves as the optimized strategy, while for a heterogeneous environment, we find that the optimized strategy involves a combination of directed and random migrations. The relative contribution of these modes is determined by the density of obstacles and motility of targets. Existence of randomness and motility of targets add to the efficiency of search. Our study reveals generic and simple rules that govern search efficiency. Our findings might find application in a number of areas including immunology, cell biology, ecology, and robotics.

  16. Signal and data processing of small targets 1989; Proceedings of the Meeting, Orlando, FL, Mar. 27-29, 1989

    Science.gov (United States)

    Drummond, Oliver E. (Editor)

    1989-01-01

    The present conference on digital signal processing, association and filtering techniques, and multiple-sensor/multiple-tracking techniques, discusses single-frame velocity estimation, efficient target extraction for laser radar imagery, precision target tracking for small extended objects, IR clutter partitioning for matched filter design, the maximum-likelihood approach to gamma circumvention, position estimation for optical point targets using staring detector arrays, and a multiple-scan signal processing technique for area-moving target indication. Also discussed are a proportional integral estimator, the prediction of track purity in tracking performance evaluations, synchronization and fault-tolerance in a distributed tracker, the benefits of soft sensors and probabilistic fusion, and testing track initiation algorithms fusing two-dimensional tracks.

  17. 77 FR 13656 - Call for Papers: National Symposium on Moving Target Research

    Science.gov (United States)

    2012-03-07

    ... a dynamic attack surface to an adversary, increasing the work factor necessary to successfully attack and exploit a cyber target. Throughout the federal government, research related to MT has been... improvement in the defense of cyber systems (a game changer),'' including how to develop better measures of...

  18. Is perception of self-motion speed a necessary condition for intercepting a moving target while walking?

    Science.gov (United States)

    Morice, Antoine H P; Wallet, Grégory; Montagne, Gilles

    2014-04-30

    While it has been shown that the Global Optic Flow Rate (GOFR) is used in the control of self-motion speed, this study examined its relevance in the control of interceptive actions while walking. We asked participants to intercept approaching targets by adjusting their walking speed in a virtual environment, and predicted that the influence of the GOFR depended on their interception strategy. Indeed, unlike the Constant Bearing Angle (CBA), the Modified Required Velocity (MRV) strategy relies on the perception of self-displacement speed. On the other hand, the CBA strategy involves specific speed adjustments depending on the curvature of the target's trajectory, whereas the MRV does not. We hypothesized that one strategy is selected among the two depending on the informational content of the environment. We thus manipulated the curvature and display of the target's trajectory, and the relationship between physical walking speed and the GOFR (through eye height manipulations). Our results showed that when the target trajectory was not displayed, walking speed profiles were affected by curvature manipulations. Otherwise, walking speed profiles were less affected by curvature manipulations and were affected by the GOFR manipulations. Taken together, these results show that the use of the GOFR for intercepting a moving target while walking depends on the informational content of the environment. Finally we discuss the complementary roles of these two perceptual-motor strategies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. High-Performance Small-Scale Solvers for Moving Horizon Estimation

    DEFF Research Database (Denmark)

    Frison, Gianluca; Vukov, Milan; Poulsen, Niels Kjølstad

    2015-01-01

    implementation techniques focusing on small-scale problems. The proposed MHE solver is implemented using custom linear algebra routines and is compared against implementations using BLAS libraries. Additionally, the MHE solver is interfaced to a code generation tool for nonlinear model predictive control (NMPC...

  20. Joint synthetic aperture radar plus ground moving target indicator from single-channel radar using compressive sensing

    Science.gov (United States)

    Thompson, Douglas; Hallquist, Aaron; Anderson, Hyrum

    2017-10-17

    The various embodiments presented herein relate to utilizing an operational single-channel radar to collect and process synthetic aperture radar (SAR) and ground moving target indicator (GMTI) imagery from a same set of radar returns. In an embodiment, data is collected by randomly staggering a slow-time pulse repetition interval (PRI) over a SAR aperture such that a number of transmitted pulses in the SAR aperture is preserved with respect to standard SAR, but many of the pulses are spaced very closely enabling movers (e.g., targets) to be resolved, wherein a relative velocity of the movers places them outside of the SAR ground patch. The various embodiments of image reconstruction can be based on compressed sensing inversion from undersampled data, which can be solved efficiently using such techniques as Bregman iteration. The various embodiments enable high-quality SAR reconstruction, and high-quality GMTI reconstruction from the same set of radar returns.

  1. A Novel Method for Proximity Detection of Moving Targets Using a Large-Scale Planar Capacitive Sensor System

    Directory of Open Access Journals (Sweden)

    Yong Ye

    2016-05-01

    Full Text Available A novel method for proximity detection of moving targets (with high dielectric constants using a large-scale (the size of each sensor is 31 cm × 19 cm planar capacitive sensor system (PCSS is proposed. The capacitive variation with distance is derived, and a pair of electrodes in a planar capacitive sensor unit (PCSU with a spiral shape is found to have better performance on sensitivity distribution homogeneity and dynamic range than three other shapes (comb shape, rectangular shape, and circular shape. A driving excitation circuit with a Clapp oscillator is proposed, and a capacitance measuring circuit with sensitivity of 0.21 V p − p / pF is designed. The results of static experiments and dynamic experiments demonstrate that the voltage curves of static experiments are similar to those of dynamic experiments; therefore, the static data can be used to simulate the dynamic curves. The dynamic range of proximity detection for three projectiles is up to 60 cm, and the results of the following static experiments show that the PCSU with four neighboring units has the highest sensitivity (the sensitivities of other units are at least 4% lower; when the attack angle decreases, the intensity of sensor signal increases. This proposed method leads to the design of a feasible moving target detector with simple structure and low cost, which can be applied in the interception system.

  2. Non-small cell lung cancer: the era of targeted therapy

    Directory of Open Access Journals (Sweden)

    Antonoff MB

    2012-07-01

    Full Text Available Mara B Antonoff, Jonathan D'CunhaDivision of Thoracic and Foregut Surgery, Department of Surgery, University of Minnesota, Minneapolis, MN, USAAbstract: In this review, the authors aim to provide an overview of current molecular targeted therapies for NSCLC, to propose an algorithm for clinical application of presently available treatment strategies, and to identify future directions for this important area of research. Historically, choice of treatment algorithm for the management of non-small cell lung cancer (NSCLC has relied heavily upon histology and clinical staging information, typically assigning patients to surgery, chemotherapy, radiation, or a combination thereof. However, previous treatment strategies have been fraught with disappointing response rates and significant systemic toxicities. The concept of personalized therapy for NSCLC involves characterization of each individual patient's tumor, in terms of genetic aberrations and expected biologic behavior, and using this information to tailor subsequent clinical management. Several driver mutations have been identified to date in subsets of patients with NSCLC, and, by focusing on specific molecular targets, new agents have been developed with the intent of treating the cancer cells while causing minimal toxicity to benign, healthy cells. In particular, current strategies exist to identify patients with epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase rearrangements, with promising results upon clinical application of agents targeting these abnormalities. Moving forward, attempts are being made to determine comprehensive genetic and biologic characterization of individuals' NSCLC tumors and to incorporate these findings into everyday practice. The era of targeted therapy is upon us. As we seek to expand our knowledge of the specific molecular and cellular derangements leading to growth and proliferation of NSCLC tumors, our efforts bring us closer to

  3. Preparation of calcium-separated isotope targets using small samples

    International Nuclear Information System (INIS)

    Thomas, G.E.

    1975-01-01

    Targets are routinely evaporated using a few milligram quantities of separated isotopes of calcium with reducing agents. The source to target distance is 3.0 cm with the substrate, if necessary, as thin as 15 μg/cm 2 carbon or 100 μg/cm 2 of gold. A tantalum closed boat, heat shield, and special collimator system are used

  4. Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.

    Science.gov (United States)

    Patel, Shreyaskumar R

    2014-01-01

    Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.

  5. An infrared small target detection method based on multiscale local homogeneity measure

    Science.gov (United States)

    Nie, Jinyan; Qu, Shaocheng; Wei, Yantao; Zhang, Liming; Deng, Lizhen

    2018-05-01

    Infrared (IR) small target detection plays an important role in the field of image detection area owing to its intrinsic characteristics. This paper presents a multiscale local homogeneity measure (MLHM) for infrared small target detection, which can enhance the performance of IR small target detection system. Firstly, intra-patch homogeneity of the target itself and the inter-patch heterogeneity between target and the local background regions are integrated to enhance the significant of small target. Secondly, a multiscale measure based on local regions is proposed to obtain the most appropriate response. Finally, an adaptive threshold method is applied to small target segmentation. Experimental results on three different scenarios indicate that the MLHM has good performance under the interference of strong noise.

  6. The oceanic fixed nitrogen and nitrous oxide budgets: Moving targets as we enter the anthropocene?

    Directory of Open Access Journals (Sweden)

    L. A. Codispoti

    2001-12-01

    Full Text Available New data force us to raise previous estimates of oceanic denitrification. Our revised estimate of ~ 450 Tg N yr-1 (Tg = 1012 g produces an oceanic fixed N budget with a large deficit (~ 200 Tg N yr-1 that can be explained only by positing an ocean that has deviated far from a steady-state, the need for a major upwards revision of fixed N inputs, particularly nitrogen fixation, or both. Oceanic denitrification can be significantly altered by small re-distributions of carbon and dissolved oxygen. Since fixed N is a limiting nutrient, uncompensated changes in denitrification affect the ocean´s ability to sequester atmospheric CO2 via the "biological pump". We have also had to modify our concepts of the oceanic N2O regime to take better account of the extremely high N2O saturations that can arise in productive, low oxygen waters. Recent results from the western Indian Shelf during a period when hypoxic, suboxic and anoxic waters were present produced a maximum surface N2O saturation of > 8000%, a likely consequence of "stop and go" denitrification. The sensitivity of N2O production and consumption to small changes in the oceanic dissolved oxygen distribution and to the "spin-up" phase of denitrification suggests that the oceanic source term for N2O could change rapidly.

  7. Development and performance evaluation of a dynamic phantom for biological dosimetry of moving targets

    Science.gov (United States)

    Gemmel, A.; Bert, C.; Saito, N.; von Neubeck, C.; Iancu, G.; K-Weyrather, W.; Durante, M.; Rietzel, E.

    2010-06-01

    A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within ±5% of the target dose of 6 Gy (RBE).

  8. Development and performance evaluation of a dynamic phantom for biological dosimetry of moving targets

    Energy Technology Data Exchange (ETDEWEB)

    Gemmel, A; Bert, C; Saito, N; Von Neubeck, C; Iancu, G; K-Weyrather, W; Durante, M; Rietzel, E, E-mail: alexander.ag.gemmel@siemens.co [GSI Helmholtzzentrum fuer Schwerionenforschung, Planckstr 1, 64291 Darmstadt (Germany)

    2010-06-07

    A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within {+-}5% of the target dose of 6 Gy (RBE).

  9. Signal and data processing of small targets 1990; Proceedings of the Meeting, Orlando, FL, Apr. 16-18, 1990

    Science.gov (United States)

    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.

  10. Experimental research on laser tracking system with galvanometer scanner for measuring spatial coordinates of moving target

    Science.gov (United States)

    Wang, Jia; Hu, Zhaohui; Liu, Yongdong; Liang, Jinwen

    2000-10-01

    The spatial position of industrial object, such as robot end- effector, is an important geometric parameter whose accuracy determines whether robot can perform accurately. Therefore, we have established a laser tracking and coordinate measuring system with galvanometer scanner for high accuracy, large range, non- contact, and spatial dynamic measurement. In this paper, the laser tracking system and its setup are illuminated at first. Then, the formulae for calculating coordinates are deduced, and the calibration method of the initial distance from tracking mirror to target is presented. After that, two preliminary experiments in different distances are described. One is on CMM; the other is with grating ruler as reference. In the former, the maximum measurement error of coordinates is 70micrometers and the maximum error of length is 35micrometers in the 85x100x100mm3 measurement volume, and in the 1m initial distance. In the later, the maximum error of length is 140micrometers in the range of 480mm, and in the 5m initial distance. At the end of the paper, the error sources are analyzed and simulated.

  11. Robust Small Target Co-Detection from Airborne Infrared Image Sequences.

    Science.gov (United States)

    Gao, Jingli; Wen, Chenglin; Liu, Meiqin

    2017-09-29

    In this paper, a novel infrared target co-detection model combining the self-correlation features of backgrounds and the commonality features of targets in the spatio-temporal domain is proposed to detect small targets in a sequence of infrared images with complex backgrounds. Firstly, a dense target extraction model based on nonlinear weights is proposed, which can better suppress background of images and enhance small targets than weights of singular values. Secondly, a sparse target extraction model based on entry-wise weighted robust principal component analysis is proposed. The entry-wise weight adaptively incorporates structural prior in terms of local weighted entropy, thus, it can extract real targets accurately and suppress background clutters efficiently. Finally, the commonality of targets in the spatio-temporal domain are used to construct target refinement model for false alarms suppression and target confirmation. Since real targets could appear in both of the dense and sparse reconstruction maps of a single frame, and form trajectories after tracklet association of consecutive frames, the location correlation of the dense and sparse reconstruction maps for a single frame and tracklet association of the location correlation maps for successive frames have strong ability to discriminate between small targets and background clutters. Experimental results demonstrate that the proposed small target co-detection method can not only suppress background clutters effectively, but also detect targets accurately even if with target-like interference.

  12. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  13. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Science.gov (United States)

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  14. MONETARY POLICY AND INFLATION TARGETING IN A SMALL OPEN ECONOMY

    Directory of Open Access Journals (Sweden)

    Antoni Antoni

    2011-09-01

    Full Text Available The danger of inflation has been the focus of many central banks. This paper analyzes the transmission mechanism of monetary policy and inflation targeting in Malaysia with a backward-looking aggregate supply and demand analysis. The manage floating regime applied in the country has an important role in achieving a stable exchange rate against its major trading partners. It also analyzes the policy of maintaining the soundness of interest rate to perceive inflation targeting to increase its economic growth. Using 1991-2004 data and a traditional structural econometric model, it shows that output gap is important in forecasting a domestic inflation rate by controlling the interest rate.  Keywords: Inflation targeting, monetary economics, structural econometric modelJEL classification numbers: E3, E52

  15. Novel Method of Unambiguous Moving Target Detection in Pulse-Doppler Radar with Random Pulse Repetition Interval

    Directory of Open Access Journals (Sweden)

    Liu Zhen

    2012-03-01

    Full Text Available Blind zones and ambiguities in range and velocity measurement are two important issues in traditional pulse-Doppler radar. By generating random deviations with respect to a mean Pulse Repetition Interval (PRI, this paper proposes a novel algorithm of Moving Target Detection (MTD based on the Compressed Sensing (CS theory, in which the random deviations of the PRIare converted to the Restricted Isometry Property (RIP of the observing matrix. The ambiguities of range and velocity are eliminated by designing the signal parameters. The simulation results demonstrate that this scheme has high performance of detection, and there is no ambiguity and blind zones as well. It can also shorten the coherent processing interval compared to traditional staggered PRI mode because only one pulse train is needed instead of several trains.

  16. Infrared small target detection technology based on OpenCV

    Science.gov (United States)

    Liu, Lei; Huang, Zhijian

    2013-09-01

    Accurate and fast detection of infrared (IR) dim target has very important meaning for infrared precise guidance, early warning, video surveillance, etc. In this paper, some basic principles and the implementing flow charts of a series of algorithms for target detection are described. These algorithms are traditional two-frame difference method, improved three-frame difference method, background estimate and frame difference fusion method, and building background with neighborhood mean method. On the foundation of above works, an infrared target detection software platform which is developed by OpenCV and MFC is introduced. Three kinds of tracking algorithms are integrated in this software. In order to explain the software clearly, the framework and the function are described in this paper. At last, the experiments are performed for some real-life IR images. The whole algorithm implementing processes and results are analyzed, and those algorithms for detection targets are evaluated from the two aspects of subjective and objective. The results prove that the proposed method has satisfying detection effectiveness and robustness. Meanwhile, it has high detection efficiency and can be used for real-time detection.

  17. Small molecules and targeted therapies in distant metastatic disease

    DEFF Research Database (Denmark)

    Hersey, P; Bastholt, L; Chiarion-Sileni, V

    2009-01-01

    with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib...

  18. Dosimetric evaluation of a moving tumor target in intensity-modulated radiation therapy (IMRT) for lung cancer patients

    Science.gov (United States)

    Kim, Sung Kyu; Kang, Min Kyu; Yea, Ji Woon; Oh, Se An

    2013-07-01

    Immobilization plays an important role in intensity-modulated radiation therapy (IMRT). The application of IMRT in lung cancer patients is very difficult due to the movement of the tumor target. Patient setup in radiation treatment demands high accuracy because IMRT employs a treatment size of a 1mm pixel unit. Hence, quality assurance of the dose delivered to patients must be at its highest. The radiation dose was evaluated for breathing rates of 9, 14, and 18 breaths per minute (bpm) for tumor targets moving up and down by 1.0 cm and 1.5 cm. The dose of the moving planned target volume (PTV) was measured by using a thermo-luminescent dosimeter (TLD) and Gafchromic™ EBT film. The measurement points were 1.0 cm away from the top, the bottom and the left and the right sides of the PTV center. The evaluated dose differences ranged from 94.2 to 103.8%, from 94.4 to 105.4%, and from 90.7 to 108.5% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.0 cm. The mean values of the doses were 101.4, 99.9, and 99.5% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.0 cm. Meanwhile, the evaluated dose differences ranged from 93.6 to 105.8%, from 95.9 to 111.5%, and from 96.2 to 111.7% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.5 cm. The mean values of the doses were 102.3, 103.4, and 103.1% for 9, 14 and 18 bpm, respectively, for a tumor movement of 1.5 cm. Therefore, we suggest that IMRT can be used in the treatment of lung cancer patients with vertical target movements within the range of 1.0 to 1.5 cm.

  19. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.

    2009-01-01

    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

  20. Small but effective: India's targeted unconditional cash transfers

    OpenAIRE

    Puja Dutta; Stephen Howes; Rinku Murgai

    2010-01-01

    India's approach to social security stresses the provision of subsidized food and public works. Targeted, unconditional cash transfers are little used, and have been little evaluated. An evaluation of cash transfers for the elderly and widows based on national household survey data and surveys on social pension utilization in two of India's states, Karnataka and Rajasthan, reveal that these social pension schemes work reasonably well. Levels of leakage (corruption) are low, funds flow disprop...

  1. Small molecule inhibitors target the tissue transglutaminase and fibronectin interaction.

    Directory of Open Access Journals (Sweden)

    Bakhtiyor Yakubov

    Full Text Available Tissue transglutaminase (TG2 mediates protein crosslinking through generation of ε-(γ-glutamyl lysine isopeptide bonds and promotes cell adhesion through interaction with fibronectin (FN and integrins. Cell adhesion to the peritoneal matrix regulated by TG2 facilitates ovarian cancer dissemination. Therefore, disruption of the TG2-FN complex by small molecules may inhibit cell adhesion and metastasis. A novel high throughput screening (HTS assay based on AlphaLISA™ technology was developed to measure the formation of a complex between His-TG2 and the biotinylated FN fragment that binds TG2 and to discover small molecules that inhibit this protein-protein interaction. Several hits were identified from 10,000 compounds screened. The top candidates selected based on >70% inhibition of the TG2/FN complex formation were confirmed by using ELISA and bioassays measuring cell adhesion, migration, invasion, and proliferation. In conclusion, the AlphaLISA bead format assay measuring the TG2-FN interaction is robust and suitable for HTS of small molecules. One compound identified from the screen (TG53 potently inhibited ovarian cancer cell adhesion to FN, cell migration, and invasion and could be further developed as a potential inhibitor for ovarian cancer dissemination.

  2. Predicting Drug-Target Interactions Based on Small Positive Samples.

    Science.gov (United States)

    Hu, Pengwei; Chan, Keith C C; Hu, Yanxing

    2018-01-01

    A basic task in drug discovery is to find new medication in the form of candidate compounds that act on a target protein. In other words, a drug has to interact with a target and such drug-target interaction (DTI) is not expected to be random. Significant and interesting patterns are expected to be hidden in them. If these patterns can be discovered, new drugs are expected to be more easily discoverable. Currently, a number of computational methods have been proposed to predict DTIs based on their similarity. However, such as approach does not allow biochemical features to be directly considered. As a result, some methods have been proposed to try to discover patterns in physicochemical interactions. Since the number of potential negative DTIs are very high both in absolute terms and in comparison to that of the known ones, these methods are rather computationally expensive and they can only rely on subsets, rather than the full set, of negative DTIs for training and validation. As there is always a relatively high chance for negative DTIs to be falsely identified and as only partial subset of such DTIs is considered, existing approaches can be further improved to better predict DTIs. In this paper, we present a novel approach, called ODT (one class drug target interaction prediction), for such purpose. One main task of ODT is to discover association patterns between interacting drugs and proteins from the chemical structure of the former and the protein sequence network of the latter. ODT does so in two phases. First, the DTI-network is transformed to a representation by structural properties. Second, it applies a oneclass classification algorithm to build a prediction model based only on known positive interactions. We compared the best AUROC scores of the ODT with several state-of-art approaches on Gold standard data. The prediction accuracy of the ODT is superior in comparison with all the other methods at GPCRs dataset and Ion channels dataset. Performance

  3. Lactoferrin targets T cells in the small intestine

    DEFF Research Database (Denmark)

    Nielsen, Sanne Mie; Hansen, Gert Helge; Danielsen, E Michael

    2010-01-01

    BACKGROUND: Lactoferrin (Lf) belongs to the transferrin family of non-heme iron-binding proteins and is found in milk and mucosal secretions. Consequently, it is now considered a multifunctional protein mainly involved in both the innate and adaptive immune defenses of the organism against various...... explants of pig small intestine by immunofluorescence and immunogold microscopy. RESULTS: Lf rapidly bound to the brush border and subsequently appeared in punctae in the apical cytoplasm, indicating internalization into an endosomal compartment. Essentially, no labeling was detected elsewhere...

  4. Sensing across large-scale cognitive radio networks: Data processing, algorithms, and testbed for wireless tomography and moving target tracking

    Science.gov (United States)

    Bonior, Jason David

    As the use of wireless devices has become more widespread so has the potential for utilizing wireless networks for remote sensing applications. Regular wireless communication devices are not typically designed for remote sensing. Remote sensing techniques must be carefully tailored to the capabilities of these networks before they can be applied. Experimental verification of these techniques and algorithms requires robust yet flexible testbeds. In this dissertation, two experimental testbeds for the advancement of research into sensing across large-scale cognitive radio networks are presented. System architectures, implementations, capabilities, experimental verification, and performance are discussed. One testbed is designed for the collection of scattering data to be used in RF and wireless tomography research. This system is used to collect full complex scattering data using a vector network analyzer (VNA) and amplitude-only data using non-synchronous software-defined radios (SDRs). Collected data is used to experimentally validate a technique for phase reconstruction using semidefinite relaxation and demonstrate the feasibility of wireless tomography. The second testbed is a SDR network for the collection of experimental data. The development of tools for network maintenance and data collection is presented and discussed. A novel recursive weighted centroid algorithm for device-free target localization using the variance of received signal strength for wireless links is proposed. The signal variance resulting from a moving target is modeled as having contours related to Cassini ovals. This model is used to formulate recursive weights which reduce the influence of wireless links that are farther from the target location estimate. The algorithm and its implementation on this testbed are presented and experimental results discussed.

  5. Space based lidar shot pattern targeting strategies for small targets such as streams

    Science.gov (United States)

    Spiers, Gary D.

    2001-01-01

    An analysis of the effectiveness of four different types of lidar shot distribution is conducted to determine which is best for concentrating shots in a given location. A simple preemptive targeting strategy is found to work as adequately as a more involved dynamic strategy for most target sizes considered.

  6. Dual gated PET/CT imaging of small targets of the heart: method description and testing with a dynamic heart phantom.

    Science.gov (United States)

    Kokki, Tommi; Sipilä, Hannu T; Teräs, Mika; Noponen, Tommi; Durand-Schaefer, Nicolas; Klén, Riku; Knuuti, Juhani

    2010-01-01

    In PET imaging respiratory and cardiac contraction motions interfere the imaging of heart. The aim was to develop and evaluate dual gating method for improving the detection of small targets of the heart. The method utilizes two independent triggers which are sent periodically into list mode data based on respiratory and ECG cycles. An algorithm for generating dual gated segments from list mode data was developed. The test measurements showed that rotational and axial movements of point source can be separated spatially to different segments with well-defined borders. The effect of dual gating on detection of small moving targets was tested with a moving heart phantom. Dual gated images showed 51% elimination (3.6 mm out of 7.0 mm) of contraction motion of hot spot (diameter 3 mm) and 70% elimination (14 mm out of 20 mm) of respiratory motion. Averaged activity value of hot spot increases by 89% when comparing to non-gated images. Patient study of suspected cardiac sarcoidosis shows sharper spatial myocardial uptake profile and improved detection of small myocardial structures such as papillary muscles. The dual gating method improves detection of small moving targets in a phantom and it is feasible in clinical situations.

  7. Background suppression of infrared small target image based on inter-frame registration

    Science.gov (United States)

    Ye, Xiubo; Xue, Bindang

    2018-04-01

    We propose a multi-frame background suppression method for remote infrared small target detection. Inter-frame information is necessary when the heavy background clutters make it difficult to distinguish real targets and false alarms. A registration procedure based on points matching in image patches is used to compensate the local deformation of background. Then the target can be separated by background subtraction. Experiments show our method serves as an effective preliminary of target detection.

  8. In Vitro Selection and Characterization of DNA Aptamers to a Small Molecule Target.

    Science.gov (United States)

    Ruscito, Annamaria; McConnell, Erin M; Koudrina, Anna; Velu, Ranganathan; Mattice, Christopher; Hunt, Vernon; McKeague, Maureen; DeRosa, Maria C

    2017-12-14

    Aptamers, synthetic oligonucleotide-based molecular recognition probes, have found use in a wide array of biosensing technologies based on their tight and highly selective binding to a variety of molecular targets. However, the inherent challenges associated with the selection and characterization of aptamers for small molecule targets have resulted in their underrepresentation, despite the need for small molecule detection in fields such as medicine, the environment, and agriculture. This protocol describes the steps in the selection, sequencing, affinity characterization, and truncation of DNA aptamers that are specific for small molecule targets. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  9. ZD6126: A novel small molecule vascular targeting agent

    International Nuclear Information System (INIS)

    Blakey, David C.; Ashton, Susan E.; Westwood, F. Russell; Walker, Mike; Ryan, Anderson J.

    2002-01-01

    Purpose: The aim of these studies was to evaluate factors that contribute to the selectivity of the novel vascular targeting agent ZD6126. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with ZD6126 phenol, and effects on morphology, detachment, and cytotoxicity (sulforhodamine-B dye incorporation) were determined. Hras5-transformed mouse 3T3 fibroblasts were implanted s.c. in athymic nude rats, and effects on the tumor were assessed after either i.v. bolus or 24-h minipump infusion of ZD6126. Results: In vitro, ZD6126 phenol (∼0.1 μm) rapidly (<40 min) destabilized the tubulin cytoskeleton of proliferating endothelial cells, resulting in cell shape change ('rounding up') and cell detachment at noncytotoxic drug concentrations. In vivo, in rats, an i.v. bolus dose of ZD6126 (20 mg/kg) was rapidly broken down to ZD6126 phenol, which has a short plasma elimination half-life (∼1 h). Peak plasma levels of ZD6126 phenol were well above the level required to induce HUVEC morphology changes in vitro, but cytotoxic concentrations were not maintained. A single i.v. bolus dose (50 and 20 mg/kg) of ZD6126 was well tolerated and resulted in extensive central tumor necrosis in the Hras5 model. Administration of ZD6126 using a 24-h s.c. minipump resulted in decreased (∼30-fold) peak plasma levels, but maintained cytotoxic drug levels over 24 h. Infusion of 50 mg/kg ZD6126 over 24 h was not tolerated. Infusion of 20 mg/kg ZD6126 resulted in increased toxicity compared with the i.v. bolus doses of ZD6126 and did not result in any increased tumor necrosis after 24 h. Conclusion: ZD6126 phenol induces rapid morphologic changes in HUVECs at noncytotoxic drug levels. These rapid morphologic effects combined with the rapid elimination of ZD6126 phenol contribute to the selective effects of ZD6126 on tumor vasculature at well-tolerated doses

  10. Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.

    Science.gov (United States)

    Childs-Disney, Jessica L; Disney, Matthew D

    2016-01-01

    RNA has become an increasingly important target for therapeutic interventions and for chemical probes that dissect and manipulate its cellular function. Emerging targets include human RNAs that have been shown to directly cause cancer, metabolic disorders, and genetic disease. In this review, we describe various routes to obtain bioactive compounds that target RNA, with a particular emphasis on the development of small molecules. We use these cases to describe approaches that are being developed for target validation, which include target-directed cleavage, classic pull-down experiments, and covalent cross-linking. Thus, tools are available to design small molecules to target RNA and to identify the cellular RNAs that are their targets.

  11. Think big, start small, move fast a blueprint for transformation from the Mayo Clinic Center for Innovation

    CERN Document Server

    LaRusso, Nicholas; Farrugia, Gianrico

    2015-01-01

    The Only Innovation Guide You Will Ever Need--from the Award-Winning Minds at Mayo Clinic. A lot of businesspeople talk about innovation, but few companies have achieved the level of truly transformative innovation as brilliantly--or as famously--as the legendary Mayo Clinic. Introducing Think Big, Start Small, Move Fast, the first innovation guide based on the proven, decade-long program that’s made Mayo Clinic one of the most respected and successful organizations in the world. This essential must-have guide shows you how to: Inspire and ignite trailblazing innovation in your workplace Design a new business model that’s creative, collaborative, and sustainable Apply the traditional scientific method to the latest innovations in "design thinking" Build a customized toolkit of the best practices, project portfolios, and strategies Increase your innovation capacity--and watch how quickly you succeed These field-tested techniques grew out of the health care industry but are designed ...

  12. Evaluating gaze-based interface tools to facilitate point-and-select tasks with small targets

    DEFF Research Database (Denmark)

    Skovsgaard, Henrik; Mateo, Julio C.; Hansen, John Paulin

    2011-01-01

    -and-select tasks. We conducted two experiments comparing the performance of dwell, magnification and zoom methods in point-and-select tasks with small targets in single- and multiple-target layouts. Both magnification and zoom showed higher hit rates than dwell. Hit rates were higher when using magnification than...

  13. Results from the search-lidar demonstrator project for detection of small Sea-Surface targets

    NARCIS (Netherlands)

    Heuvel, J.C. van den; Putten, F.J.M. van; Cohen, L.H.; Kemp, R.A.W.; Franssen, G.C.

    2009-01-01

    Coastal surveillance and naval operations in the littoral both have to deal with the threat of small sea-surface targets. These targets have a low radar cross-section and a low velocity that makes them hard to detect by radar. Typical threats include jet skis, FIAC's, and speedboats. Previous lidar

  14. Search-Lidar Demonstrator for Detection of Small Sea-Surface Targets

    NARCIS (Netherlands)

    Heuvel, J.C. van den; Bekman, H.H.P.T.; Putten, F.J.M. van; Cohen, L.H.; Schleijpen, H.M.A.

    2008-01-01

    Coastal surveillance and naval operations in the littoral both have to deal with the threat of small sea-surface targets. These targets have a low radar cross-section and a low velocity that makes them hard to detect by radar. Typical threats include jet skis, FIAC’s, and speedboats. Lidar

  15. Detection of Small Sea-Surface Targets with a Search Lidar

    NARCIS (Netherlands)

    Heuvel, J.C. van den; Bekman, H.H.P.T.; Putten, F.J.M.; Cohen, L.A.

    2007-01-01

    Naval operations in the littoral have to deal with the threat of small sea-surface targets. These targets have a low radar cross-section and low velocity, which makes them hard to detect by radar in the presence of sea clutter. Typical threats include periscopes, jet skies, FIAC’s, and speedboats.

  16. The Moving Group Targets of the SEEDS High-contrast Imaging Survey of Exoplanets and Disks: Results and Observations from the First Three Years

    NARCIS (Netherlands)

    Brandt, T.D.; et al., [Unknown; Thalmann, C.

    2014-01-01

    We present results from the first three years of observations of moving group (MG) targets in the Strategic Exploration of Exoplanets and Disks with Subaru (SEEDS) high-contrast imaging survey of exoplanets and disks using the Subaru telescope. We achieve typical contrasts of ~105 at 1'' and ~106

  17. Detection of small targets in a marine environment using laser radar

    NARCIS (Netherlands)

    Kunz, G.J.; Bekman, H.H.P.T.; Benoist, K.W.; Cohen, L.H.; Heuvel, J.C. van den; Putten, F.J.M.

    2005-01-01

    Small maritime targets, e.g., periscope tubes, jet skies, swimmers and small boats, are potential threats for naval ships under many conditions, but are difficult to detect with current radar systems due to their limited radar cross section and the presence of sea clutter. On the other hand,

  18. Research on infrared small-target tracking technology under complex background

    Science.gov (United States)

    Liu, Lei; Wang, Xin; Chen, Jilu; Pan, Tao

    2012-10-01

    In this paper, some basic principles and the implementing flow charts of a series of algorithms for target tracking are described. On the foundation of above works, a moving target tracking software base on the OpenCV is developed by the software developing platform MFC. Three kinds of tracking algorithms are integrated in this software. These two tracking algorithms are Kalman Filter tracking method and Camshift tracking method. In order to explain the software clearly, the framework and the function are described in this paper. At last, the implementing processes and results are analyzed, and those algorithms for tracking targets are evaluated from the two aspects of subjective and objective. This paper is very significant in the application of the infrared target tracking technology.

  19. Methods to enable the design of bioactive small molecules targeting RNA.

    Science.gov (United States)

    Disney, Matthew D; Yildirim, Ilyas; Childs-Disney, Jessica L

    2014-02-21

    RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.

  20. Dynamic-MLC leaf control utilizing on-flight intensity calculations: A robust method for real-time IMRT delivery over moving rigid targets

    International Nuclear Information System (INIS)

    McMahon, Ryan; Papiez, Lech; Rangaraj, Dharanipathy

    2007-01-01

    An algorithm is presented that allows for the control of multileaf collimation (MLC) leaves based entirely on real-time calculations of the intensity delivered over the target. The algorithm is capable of efficiently correcting generalized delivery errors without requiring the interruption of delivery (self-correcting trajectories), where a generalized delivery error represents anything that causes a discrepancy between the delivered and intended intensity profiles. The intensity actually delivered over the target is continually compared to its intended value. For each pair of leaves, these comparisons are used to guide the control of the following leaf and keep this discrepancy below a user-specified value. To demonstrate the basic principles of the algorithm, results of corrected delivery are shown for a leading leaf positional error during dynamic-MLC (DMLC) IMRT delivery over a rigid moving target. It is then shown that, with slight modifications, the algorithm can be used to track moving targets in real time. The primary results of this article indicate that the algorithm is capable of accurately delivering DMLC IMRT over a rigid moving target whose motion is (1) completely unknown prior to delivery and (2) not faster than the maximum MLC leaf velocity over extended periods of time. These capabilities are demonstrated for clinically derived intensity profiles and actual tumor motion data, including situations when the target moves in some instances faster than the maximum admissible MLC leaf velocity. The results show that using the algorithm while calculating the delivered intensity every 50 ms will provide a good level of accuracy when delivering IMRT over a rigid moving target translating along the direction of MLC leaf travel. When the maximum velocities of the MLC leaves and target were 4 and 4.2 cm/s, respectively, the resulting error in the two intensity profiles used was 0.1±3.1% and -0.5±2.8% relative to the maximum of the intensity profiles. For

  1. Economic assessments of small-scale drinking-water interventions in pursuit of MDG target 7C.

    Science.gov (United States)

    Cameron, John; Jagals, Paul; Hunter, Paul R; Pedley, Steve; Pond, Katherine

    2011-12-01

    This paper uses an applied rural case study of a safer water intervention in South Africa to illustrate how three levels of economic assessment can be used to understand the impact of the intervention on people's well-being. It is set in the context of Millennium Development Goal 7 which sets a target (7C) for safe drinking-water provision and the challenges of reaching people in remote rural areas with relatively small-scale schemes. The assessment moves from cost efficiency to cost effectiveness to a full social cost-benefit analysis (SCBA) with an associated sensitivity test. In addition to demonstrating techniques of analysis, the paper brings out many of the challenges in understanding how safer drinking-water impacts on people's livelihoods. The SCBA shows the case study intervention is justified economically, though the sensitivity test suggests 'downside' vulnerability. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. High-resolution remotely sensed small target detection by imitating fly visual perception mechanism.

    Science.gov (United States)

    Huang, Fengchen; Xu, Lizhong; Li, Min; Tang, Min

    2012-01-01

    The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

  3. High-Resolution Remotely Sensed Small Target Detection by Imitating Fly Visual Perception Mechanism

    Directory of Open Access Journals (Sweden)

    Fengchen Huang

    2012-01-01

    Full Text Available The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

  4. Online virtual isocenter based radiation field targeting for high performance small animal microirradiation

    Science.gov (United States)

    Stewart, James M. P.; Ansell, Steve; Lindsay, Patricia E.; Jaffray, David A.

    2015-12-01

    Advances in precision microirradiators for small animal radiation oncology studies have provided the framework for novel translational radiobiological studies. Such systems target radiation fields at the scale required for small animal investigations, typically through a combination of on-board computed tomography image guidance and fixed, interchangeable collimators. Robust targeting accuracy of these radiation fields remains challenging, particularly at the millimetre scale field sizes achievable by the majority of microirradiators. Consistent and reproducible targeting accuracy is further hindered as collimators are removed and inserted during a typical experimental workflow. This investigation quantified this targeting uncertainty and developed an online method based on a virtual treatment isocenter to actively ensure high performance targeting accuracy for all radiation field sizes. The results indicated that the two-dimensional field placement uncertainty was as high as 1.16 mm at isocenter, with simulations suggesting this error could be reduced to 0.20 mm using the online correction method. End-to-end targeting analysis of a ball bearing target on radiochromic film sections showed an improved targeting accuracy with the three-dimensional vector targeting error across six different collimators reduced from 0.56+/- 0.05 mm (mean  ±  SD) to 0.05+/- 0.05 mm for an isotropic imaging voxel size of 0.1 mm.

  5. Positron emission tomography for the dose monitoring of intra-fractionally moving targets in ion beam therapy

    International Nuclear Information System (INIS)

    Stuetzer, Kristin

    2014-01-01

    successful reduction of motion artefacts. The therapy control system provides information about the exact progress of the motion compensated dose delivery. Recommendations are given in this thesis to optimize the 4D IBT-PET workflow and to prevent the observer from a mis-interpretation of the dose monitoring data. In summary, the thesis contributes on a large scale to a potential future application of the IBT-PET monitoring for intra-fractionally moving target volumes by providing the required reconstruction and simulation algorithms. Systematic examinations with more realistic, multi-directional and irregular motion patterns are required for further improvements.

  6. Evaluation of a novel ultra small target technology supporting on-product overlay measurements

    Science.gov (United States)

    Smilde, Henk-Jan H.; den Boef, Arie; Kubis, Michael; Jak, Martin; van Schijndel, Mark; Fuchs, Andreas; van der Schaar, Maurits; Meyer, Steffen; Morgan, Stephen; Wu, Jon; Tsai, Vincent; Wang, Cathy; Bhattacharyya, Kaustuve; Chen, Kai-Hsiung; Huang, Guo-Tsai; Ke, Chih-Ming; Huang, Jacky

    2012-03-01

    Reducing the size of metrology targets is essential for in-die overlay metrology in advanced semiconductor manufacturing. In this paper, μ-diffraction-based overlay (μDBO) measurements with a YieldStar metrology tool are presented for target-sizes down to 10 × 10 μm2. The μDBO technology enables selection of only the diffraction efficiency information from the grating by efficiently separating it from product structure reflections. Therefore, μDBO targets -even when located adjacent to product environment- give excellent correlation with 40 × 160 μm2 reference targets. Although significantly smaller than standard scribe-line targets, they can achieve total-measurement-uncertainty values of below 0.5 nm on a wide range of product layers. This shows that the new μDBO technique allows for accurate metrology on ultra small in-die targets, while retaining the excellent TMU performance of diffraction-based overlay metrology.

  7. Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384.

    Science.gov (United States)

    An, Guohua; Liu, Wei; Dutta, Sandeep

    2015-10-01

    Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example. © 2015, The American College of Clinical Pharmacology.

  8. Small-Molecule Compounds Exhibiting Target-Mediated Drug Disposition (TMDD): A Minireview.

    Science.gov (United States)

    An, Guohua

    2017-02-01

    Nonlinearities are commonplace in pharmacokinetics, and 1 special source is the saturable binding of the drug to a high-affinity, low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Compared with large-molecule compounds undergoing TMDD, which has been well recognized due to its high prevalence, TMDD in small-molecule compounds is more counterintuitive and has not been well appreciated. With more and more potent small-molecule drugs acting on highly specific targets being developed as well as increasingly sensitive analytical techniques becoming available, many small-molecule compounds have recently been reported to have nonlinear pharmacokinetics imparted by TMDD. To expand our current knowledge of TMDD in small-molecule compounds and increase the awareness of this clinically important phenomenon, this minireview provides an overview of the small-molecule compounds that demonstrate nonlinear pharmacokinetics imparted by TMDD. The present review also summarizes the general features of TMDD in small-molecule compounds and highlights the differences between TMDD in small-molecule compounds and large-molecule compounds. © 2016, The American College of Clinical Pharmacology.

  9. A case study in adaptable and reusable infrastructure at the Keck Observatory Archive: VO interfaces, moving targets, and more

    Science.gov (United States)

    Berriman, G. Bruce; Cohen, Richard W.; Colson, Andrew; Gelino, Christopher R.; Good, John C.; Kong, Mihseh; Laity, Anastasia C.; Mader, Jeffrey A.; Swain, Melanie A.; Tran, Hien D.; Wang, Shin-Ywan

    2016-08-01

    searches are spatial, much of the effort in developing the program interface involved processing the instrument and telescope parameters to understand how accurately we can derive the WCS information for each instrument. This knowledge is now being fed back into the KOA databases as part of a program to include complete metadata information for all imaging observations. The R-tree program was itself extended to support temporal (in addition to spatial) indexing, in response to requests from the planetary science community for a search engine to discover observations of Solar System objects. With this 3D-indexing scheme, the service performs very fast time and spatial matches between the target ephemerides, obtained from the JPL SPICE service. Our experiments indicate these matches can be more than 100 times faster than when separating temporal and spatial searches. Images of the tracks of the moving targets, overlaid with the image footprints, are computed with a new command-line visualization tool, mViewer, released with the Montage distribution. The service is currently in test and will be released in late summer 2016.

  10. Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

    Directory of Open Access Journals (Sweden)

    Shan L

    2015-09-01

    Full Text Available Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX, composed of folic acid (FA, target, amino acids (Arg or Glu, linker, and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy

  11. Small Open Economies with Frictions in Credit Markets: Target inflation or money growth when floating?

    OpenAIRE

    Paula Hernandez-Verme

    2009-01-01

    I compare the relative merits of a policy of inflation targeting for small open economies with frictions in financial markets with an alternative floating regime that has a constant rate of domestic money growth. The differences between these two policies appear only in the dynamic properties of equilibria with credit rationing. When the probability of loan repayment is low, inflation targeting eliminates endogenous volatility when compared with a constant money growth, but equilibria remain ...

  12. An ML-Based Radial Velocity Estimation Algorithm for Moving Targets in Spaceborne High-Resolution and Wide-Swath SAR Systems

    Directory of Open Access Journals (Sweden)

    Tingting Jin

    2017-04-01

    Full Text Available Multichannel synthetic aperture radar (SAR is a significant breakthrough to the inherent limitation between high-resolution and wide-swath (HRWS compared with conventional SAR. Moving target indication (MTI is an important application of spaceborne HRWS SAR systems. In contrast to previous studies of SAR MTI, the HRWS SAR mainly faces the problem of under-sampled data of each channel, causing single-channel imaging and processing to be infeasible. In this study, the estimation of velocity is equivalent to the estimation of the cone angle according to their relationship. The maximum likelihood (ML based algorithm is proposed to estimate the radial velocity in the existence of Doppler ambiguities. After that, the signal reconstruction and compensation for the phase offset caused by radial velocity are processed for a moving target. Finally, the traditional imaging algorithm is applied to obtain a focused moving target image. Experiments are conducted to evaluate the accuracy and effectiveness of the estimator under different signal-to-noise ratios (SNR. Furthermore, the performance is analyzed with respect to the motion ship that experiences interference due to different distributions of sea clutter. The results verify that the proposed algorithm is accurate and efficient with low computational complexity. This paper aims at providing a solution to the velocity estimation problem in the future HRWS SAR systems with multiple receive channels.

  13. Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators

    NARCIS (Netherlands)

    Rwigema, Jean-Claude M.; Beck, Barbara; Wang, Wei; Doemling, Alexander; Epperly, Michael W.; Shields, Donna; Goff, Julie P.; Franicola, Darcy; Dixon, Tracy; Frantz, Marie-Céline; Wipf, Peter; Tyurina, Yulia; Kagan, Valerian E.; Wang, Hong; Greenberger, Joel S.

    2011-01-01

    Purpose: To evaluate the effectiveness of mitigation of acute ionizing radiation damage by mitochondrion-targeted small molecules. Methods and Materials: We evaluated the ability of nitroxide-linked alkene peptide isostere JP4-039, the nitric oxide synthase inhibitor-linked alkene peptide esostere

  14. Region descriptors for automatic classification of small sea targets in infrared video

    NARCIS (Netherlands)

    Mouthaan, M.M.; Broek, S.P. van den; Hendriks, E.A.; Schwering, P.B.W.

    2011-01-01

    We evaluate the performance of different key-point detectors and region descriptors when used for automatic classification of small sea targets in infrared video. In our earlier research performed on this subject as well as in other literature, many different region descriptors have been proposed.

  15. Hadron-nucleus interactions with a small target-nucleus excitation

    International Nuclear Information System (INIS)

    Anzon, Z.V.; Chasnikov, I.Ya.; Shakhova, Ts.I.

    1981-01-01

    Hadron inelastic interactions in nuclear emulsion with a small target-nucleus excitation in the energy range 7.5-200 GeV have been studied. Possible reasons for the differences in production cross-section for events with even and odd number of S-particles are analysed

  16. StarScan: a web server for scanning small RNA targets from degradome sequencing data.

    Science.gov (United States)

    Liu, Shun; Li, Jun-Hao; Wu, Jie; Zhou, Ke-Ren; Zhou, Hui; Yang, Jian-Hua; Qu, Liang-Hu

    2015-07-01

    Endogenous small non-coding RNAs (sRNAs), including microRNAs, PIWI-interacting RNAs and small interfering RNAs, play important gene regulatory roles in animals and plants by pairing to the protein-coding and non-coding transcripts. However, computationally assigning these various sRNAs to their regulatory target genes remains technically challenging. Recently, a high-throughput degradome sequencing method was applied to identify biologically relevant sRNA cleavage sites. In this study, an integrated web-based tool, StarScan (sRNA target Scan), was developed for scanning sRNA targets using degradome sequencing data from 20 species. Given a sRNA sequence from plants or animals, our web server performs an ultrafast and exhaustive search for potential sRNA-target interactions in annotated and unannotated genomic regions. The interactions between small RNAs and target transcripts were further evaluated using a novel tool, alignScore. A novel tool, degradomeBinomTest, was developed to quantify the abundance of degradome fragments located at the 9-11th nucleotide from the sRNA 5' end. This is the first web server for discovering potential sRNA-mediated RNA cleavage events in plants and animals, which affords mechanistic insights into the regulatory roles of sRNAs. The StarScan web server is available at http://mirlab.sysu.edu.cn/starscan/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Design and implement of infrared small target real-time detection system based on pipeline technology

    Science.gov (United States)

    Sun, Lihui; Wang, Yongzhong; He, Yongqiang

    2007-01-01

    The detection for motive small target in infrared image sequence has become a hot topic nowadays. Background suppress algorithm based on minim gradient median filter and temporal recursion target detection algorithm are introduced. On the basis of contents previously mentioned, a four stages pipeline structure infrared small target detection process system, which aims at characters of algorithm complexity, large amounts of data to process, high frame frequency and exigent real-time character in this kind of application, is designed and implemented. The logical structure of the system was introduced and the function and signals flows are programmed. The system is composed of two FPGA chips and two DSP chips of TI. According to the function of each part, the system is divided into image preprocess stage, target detection stage, track relation stage and image output stage. The experiment of running algorithms on the system presented in this paper proved that the system could meet acquisition and process of 50Hz 240x320 digital image and the system could real time detect small target with a signal-noise ratio more than 3 reliably. The system achieves the characters of large amount of memory, high real-time processing, excellent extension and favorable interactive interface.

  18. Scale invariant SURF detector and automatic clustering segmentation for infrared small targets detection

    Science.gov (United States)

    Zhang, Haiying; Bai, Jiaojiao; Li, Zhengjie; Liu, Yan; Liu, Kunhong

    2017-06-01

    The detection and discrimination of infrared small dim targets is a challenge in automatic target recognition (ATR), because there is no salient information of size, shape and texture. Many researchers focus on mining more discriminative information of targets in temporal-spatial. However, such information may not be available with the change of imaging environments, and the targets size and intensity keep changing in different imaging distance. So in this paper, we propose a novel research scheme using density-based clustering and backtracking strategy. In this scheme, the speeded up robust feature (SURF) detector is applied to capture candidate targets in single frame at first. And then, these points are mapped into one frame, so that target traces form a local aggregation pattern. In order to isolate the targets from noises, a newly proposed density-based clustering algorithm, fast search and find of density peak (FSFDP for short), is employed to cluster targets by the spatial intensive distribution. Two important factors of the algorithm, percent and γ , are exploited fully to determine the clustering scale automatically, so as to extract the trace with highest clutter suppression ratio. And at the final step, a backtracking algorithm is designed to detect and discriminate target trace as well as to eliminate clutter. The consistence and continuity of the short-time target trajectory in temporal-spatial is incorporated into the bounding function to speed up the pruning. Compared with several state-of-arts methods, our algorithm is more effective for the dim targets with lower signal-to clutter ratio (SCR). Furthermore, it avoids constructing the candidate target trajectory searching space, so its time complexity is limited to a polynomial level. The extensive experimental results show that it has superior performance in probability of detection (Pd) and false alarm suppressing rate aiming at variety of complex backgrounds.

  19. Automatically detect and track infrared small targets with kernel Fukunaga-Koontz transform and Kalman prediction

    Science.gov (United States)

    Liu, Ruiming; Liu, Erqi; Yang, Jie; Zeng, Yong; Wang, Fanglin; Cao, Yuan

    2007-11-01

    Fukunaga-Koontz transform (FKT), stemming from principal component analysis (PCA), is used in many pattern recognition and image-processing fields. It cannot capture the higher-order statistical property of natural images, so its detection performance is not satisfying. PCA has been extended into kernel PCA in order to capture the higher-order statistics. However, thus far there have been no researchers who have definitely proposed kernel FKT (KFKT) and researched its detection performance. For accurately detecting potential small targets from infrared images, we first extend FKT into KFKT to capture the higher-order statistical properties of images. Then a framework based on Kalman prediction and KFKT, which can automatically detect and track small targets, is developed. Results of experiments show that KFKT outperforms FKT and the proposed framework is competent to automatically detect and track infrared point targets.

  20. Directional support value of Gaussian transformation for infrared small target detection.

    Science.gov (United States)

    Yang, Changcai; Ma, Jiayi; Qi, Shengxiang; Tian, Jinwen; Zheng, Sheng; Tian, Xin

    2015-03-20

    Robust small target detection is one of the key techniques in IR search and tracking systems for self-defense or attacks. In this paper we present a robust solution for small target detection in a single IR image. The key ideas of the proposed method are to use the directional support value of Gaussian transform (DSVoGT) to enhance the targets, and use the multiscale representation provided by DSVoGT to reduce the false alarm rate. The original image is decomposed into sub-bands in different orientations by convolving the image with the directional support value filters, which are deduced from the weighted mapped least-squares-support vector machines (LS-SVMs). Based on the sub-band images, a support value of Gaussian matrix is constructed, and the trace of this matrix is then defined as the target measure. The corresponding multiscale correlations of the target measures are computed for enhancing target signal while suppressing the background clutter. We demonstrate the advantages of the proposed method on real IR images and compare the results against those obtained from standard detection approaches, including the top-hat filter, max-mean filter, max-median filter, min-local-Laplacian of Gaussian (LoG) filter, as well as LS-SVM. The experimental results on various cluttered background images show that the proposed method outperforms other detectors.

  1. Will musculoskeletal and visual stress change when Visual Display Unit (VDU) operators move from small offices to an ergonomically optimized office landscape?

    Science.gov (United States)

    Helland, Magne; Horgen, Gunnar; Kvikstad, Tor Martin; Garthus, Tore; Aarås, Arne

    2011-11-01

    This study investigated the effect of moving from small offices to a landscape environment for 19 Visual Display Unit (VDU) operators at Alcatel Denmark AS. The operators reported significantly improved lighting condition and glare situation. Further, visual discomfort was also significantly reduced on a Visual Analogue Scale (VAS). There was no significant correlation between lighting condition and visual discomfort neither in the small offices nor in the office landscape. However, visual discomfort correlated significantly with glare in small offices i.e. more glare is related to more visual discomfort. This correlation disappeared after the lighting system in the office landscape had been improved. There was also a significant correlation between glare and itching of the eyes as well as blurred vision in the small offices, i.e. more glare more visual symptoms. Experience of pain was found to reduce the subjective assessment of work capacity during VDU tasks. There was a significant correlation between visual discomfort and reduced work capacity in small offices and in the office landscape. When moving from the small offices to the office landscape, there was a significant reduction in headache as well as back pain. No significant changes in pain intensity in the neck, shoulder, forearm, and wrist/hand were observed. The pain levels in different body areas were significantly correlated with subjective assessment of reduced work capacity in small offices and in the office landscape. By careful design and construction of an office landscape with regard to lighting and visual conditions, transfer from small offices may be acceptable from a visual-ergonomic point of view. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  2. Epidermal Growth Factor Receptor targeting in non-small cell lung cancer: revisiting different strategies against the same target.

    Science.gov (United States)

    Castañón, Eduardo; Martín, Patricia; Rolfo, Christian; Fusco, Juan P; Ceniceros, Lucía; Legaspi, Jairo; Santisteban, Marta; Gil-Bazo, Ignacio

    2014-01-01

    Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.

  3. Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

    2016-08-01

    Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

  4. Advances in targeted delivery of small interfering RNA using simple bioconjugates

    DEFF Research Database (Denmark)

    Nielsen, Christoffer; Kjems, Jørgen; Sorensen, Kristine Rothaus

    2014-01-01

    with a targeting moiety, in a simple bioconjugate construct. We discuss the use of different types of targeting moieties, as well as the different conjugation strategies employed for preparing these bioconjugate constructs that deliver the siRNA to target cells. We focus especially on the in-built or passive......Introduction: Development of drugs based on RNA interference by small interfering RNA (siRNA) has been progressing slowly due to a number of challenges associated with the in vivo behavior of siRNA. A central problem is controlling siRNA delivery to specific cell types. Here, we review existing...... literature on one type of strategy for solving the issue of cell-specific delivery of siRNA, namely delivering the siRNA as part of simple bioconjugate constructs. Areas covered: This review presents current experience from strategies aimed at targeting siRNA to specific cell types, by associating the siRNA...

  5. Using four-dimensional computed tomography images to optimize the internal target volume when using volume-modulated arc therapy to treat moving targets.

    Science.gov (United States)

    Yakoumakis, Nikolaos; Winey, Brian; Killoran, Joseph; Mayo, Charles; Niedermayr, Thomas; Panayiotakis, George; Lingos, Tania; Court, Laurence

    2012-11-08

    In this work we used 4D dose calculations, which include the effects of shape deformations, to investigate an alternative approach to creating the ITV. We hypothesized that instead of needing images from all the breathing phases in the 4D CT dataset to create the outer envelope used for treatment planning, it is possible to exclude images from the phases closest to the inhale phase. We used 4D CT images from 10 patients with lung cancer. For each patient, we drew a gross tumor volume on the exhale-phase image and propagated this to the images from other phases in the 4D CT dataset using commercial image registration software. We created four different ITVs using the N phases closest to the exhale phase (where N = 10, 8, 7, 6). For each ITV contour, we created a volume-modulated arc therapy plan on the exhale-phase CT and normalized it so that the prescribed dose covered at least 95% of the ITV. Each plan was applied to CT images from each CT phase (phases 1-10), and the calculated doses were then mapped to the exhale phase using deformable registration. The effect of the motion was quantified using the dose to 95% of the target on the exhale phase (D95) and tumor control probability. For the three-dimensional and 4D dose calculations of the plan where N = 10, differences in the D95 value varied from 3% to 14%, with an average difference of 7%. For 9 of the 10 patients, the reduction in D95 was less than 5% if eight phases were used to create the ITV. For three of the 10 patients, the reduction in the D95 was less than 5% if seven phases were used to create the ITV. We were unsuccessful in creating a general rule that could be used to create the ITV. Some reduction (8/10 phases) was possible for most, but not all, of the patients, and the ITV reduction was small.

  6. Using four‐dimensional computed tomography images to optimize the internal target volume when using volume‐modulated arc therapy to treat moving targets

    Science.gov (United States)

    Yakoumakis, Nikolaos; Winey, Brian; Killoran, Joseph; Mayo, Charles; Niedermayr, Thomas; Panayiotakis, George; Lingos, Tania; Court, Laurence

    2012-01-01

    In this work we used 4D dose calculations, which include the effects of shape deformations, to investigate an alternative approach to creating the ITV. We hypothesized that instead of needing images from all the breathing phases in the 4D CT dataset to create the outer envelope used for treatment planning, it is possible to exclude images from the phases closest to the inhale phase. We used 4D CT images from 10 patients with lung cancer. For each patient, we drew a gross tumor volume on the exhale‐phase image and propagated this to the images from other phases in the 4D CT dataset using commercial image registration software. We created four different ITVs using the N phases closest to the exhale phase (where N=10, 8, 7, 6). For each ITV contour, we created a volume‐modulated arc therapy plan on the exhale‐phase CT and normalized it so that the prescribed dose covered at least 95% of the ITV. Each plan was applied to CT images from each CT phase (phases 1–10), and the calculated doses were then mapped to the exhale phase using deformable registration. The effect of the motion was quantified using the dose to 95% of the target on the exhale phase (D95) and tumor control probability. For the three‐dimensional and 4D dose calculations of the plan where N=10, differences in the D95 value varied from 3% to 14%, with an average difference of 7%. For 9 of the 10 patients, the reduction in D95 was less than 5% if eight phases were used to create the ITV. For three of the 10 patients, the reduction in the D95 was less than 5% if seven phases were used to create the ITV. We were unsuccessful in creating a general rule that could be used to create the ITV. Some reduction (8/10 phases) was possible for most, but not all, of the patients, and the ITV reduction was small. PACS number: 87.55.D‐ PMID:23149778

  7. A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

    Directory of Open Access Journals (Sweden)

    Han CY

    2013-04-01

    Full Text Available Cui-yan Han,1,2 Li-ling Yue,2 Ling-yu Tai,1 Li Zhou,2 Xue-yan Li,2 Gui-hua Xing,2 Xing-gang Yang,1 Ming-shuang Sun,1 Wei-san Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Qiqihar Medical University, Qiqihar, People’s Republic of China Abstract: The epidermal growth factor receptor (EGFR serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy. Keywords: EGFR, small peptide, tumor targeting, lung cancer, NLC

  8. Dim small targets detection based on self-adaptive caliber temporal-spatial filtering

    Science.gov (United States)

    Fan, Xiangsuo; Xu, Zhiyong; Zhang, Jianlin; Huang, Yongmei; Peng, Zhenming

    2017-09-01

    To boost the detect ability of dim small targets, this paper began by using improved anisotropy for background prediction (IABP), followed by target enhancement by improved high-order cumulates (HQS). Finally, on the basis of image pre-processing, to address the problem of missed and wrong detection caused by fixed caliber of traditional pipeline filtering, this paper used targets' multi-frame movement correlation in the time-space domain, combined with the scale-space theory, to propose a temporal-spatial filtering algorithm which allows the caliber to make self-adaptive changes according to the changes of the targets' scale, effectively solving the detection-related issues brought by unchanged caliber and decreased/increased size of the targets. Experiments showed that the improved anisotropic background predication could be loyal to the true background of the original image to the maximum extent, presenting a superior overall performance to other background prediction methods; the improved HQS significantly increased the signal-noise ratio of images; when the signal-noise ratio was lower than 2.6 dB, this detection algorithm could effectively eliminate noise and detect targets. For the algorithm, the lowest signal-to-noise ratio of the detectable target is 0.37.

  9. Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Kwiatkowski, Nicholas; Abraham, Brian J

    2014-01-01

    Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive...... to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability...

  10. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Moving Targets and Biodiversity Offsets for Endangered Species Habitat: Is Lesser Prairie Chicken Habitat a Stock or Flow?

    Directory of Open Access Journals (Sweden)

    Todd K. BenDor

    2014-03-01

    Full Text Available The US Fish and Wildlife Service will make an Endangered Species Act listing decision for the lesser prairie chicken (Tympanuchus pallidicinctus; “LPC” in March 2014. Based on the findings of a single, Uzbek antelope study, conservation plans put forth for the LPC propose to modify and re-position habitat in the landscape through a series of temporary preservation/restoration efforts. We argue that for certain species, including the LPC, dynamic habitat offsets represent a dangerous re-interpretation of habitat provision and recovery programs, which have nearly-universally viewed ecosystem offsets (habitat, wetlands, streams, etc. as “stocks” that accumulate characteristics over time. Any effort to create a program of temporary, moving habitat offsets must consider species’ (1 life history characteristics, (2 behavioral tendencies (e.g., avoidance of impacted areas, nesting/breeding site fidelity, and (3 habitat restoration characteristics, including long temporal lags in reoccupation. If misapplied, species recovery programs using temporary, moving habitat risk further population declines.

  12. The Moving Group Targets of the Seeds High-Contrast Imaging Survey of Exoplanets and Disks: Results and Observations from the First Three Years

    Science.gov (United States)

    Brandt, Timothy D.; Kuzuhara, Masayuki; McElwain, Michael W.; Schlieder, Joshua E.; Wisniewski, John P.; Turner, Edwin L.; Carson, J.; Matsuo, T.; Biller, B.; Bonnefoy, M.; hide

    2014-01-01

    We present results from the first three years of observations of moving group (MG) targets in the Strategic Exploration of Exoplanets and Disks with Subaru (SEEDS) high-contrast imaging survey of exoplanets and disks using the Subaru telescope. We achieve typical contrasts of (is) approximately10(exp 5) at 1" and (is) approximately 10(exp 6) beyond 2" around 63 proposed members of nearby kinematic MGs. We review each of the kinematic associations to which our targets belong, concluding that five, beta Pictoris ((is) approximately 20 Myr), AB Doradus ((is) approximately 100 Myr), Columba ((is) approximately 30 Myr), Tucana-Horogium ((is) approximately 30 Myr), and TW Hydrae ((is) approximately 10 Myr), are sufficiently well-defined to constrain the ages of individual targets. Somewhat less than half of our targets are high-probability members of one of these MGs. For all of our targets, we combine proposed MG membership with other age indicators where available, including Ca ii HK emission, X-ray activity, and rotation period, to produce a posterior probability distribution of age. SEEDS observations discovered a substellar companion to one of our targets, kappa And, a late B star. We do not detect any other substellar companions, but do find seven new close binary systems, of which one still needs to be confirmed. A detailed analysis of the statistics of this sample, and of the companion mass constraints given our age probability distributions and exoplanet cooling models, will be presented in a forthcoming paper.

  13. Infrared dim small target segmentation method based on ALI-PCNN model

    Science.gov (United States)

    Zhao, Shangnan; Song, Yong; Zhao, Yufei; Li, Yun; Li, Xu; Jiang, Yurong; Li, Lin

    2017-10-01

    Pulse Coupled Neural Network (PCNN) is improved by Adaptive Lateral Inhibition (ALI), while a method of infrared (IR) dim small target segmentation based on ALI-PCNN model is proposed in this paper. Firstly, the feeding input signal is modulated by lateral inhibition network to suppress background. Then, the linking input is modulated by ALI, and linking weight matrix is generated adaptively by calculating ALI coefficient of each pixel. Finally, the binary image is generated through the nonlinear modulation and the pulse generator in PCNN. The experimental results show that the segmentation effect as well as the values of contrast across region and uniformity across region of the proposed method are better than the OTSU method, maximum entropy method, the methods based on conventional PCNN and visual attention, and the proposed method has excellent performance in extracting IR dim small target from complex background.

  14. Synthesis and functionalization of persistent luminescence nanoparticles with small molecules and evaluation of their targeting ability.

    Science.gov (United States)

    Maldiney, Thomas; Byk, Gerardo; Wattier, Nicolas; Seguin, Johanne; Khandadash, Raz; Bessodes, Michel; Richard, Cyrille; Scherman, Daniel

    2012-02-14

    We have recently reported the design and use of inorganic nanoparticles with persistent luminescence properties. Such nanoparticles can be excited with a UV lamp for 2min and emit light in the near-infrared area for dozen of minutes without any further excitation. This property is of particular interest for small animal optical imaging, since it avoids the autofluorescence of endogenous fluorophores which is one major problem encountered when using fluorescent probes. We report herein the synthesis of persistent luminescence nanoparticles (PLNPs) and their functionalization with two small targeting molecules: biotin and Rak-2. We provide characterization of each PLNP as well as preliminary evidence of the ability of PLNP-PEG-Biotin to target streptavidin and PLNP-PEG-Rak-2 to bind prostate cancer cells in vitro. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Target volume determination in radiotherapy for non-small-cell lung cancer-facts and questions

    International Nuclear Information System (INIS)

    Kepka, L.; Bujko, K.

    2003-01-01

    Although the precise target volume definition in conformal radiotherapy is required by ICRU Report 50 and 62, this task in radiotherapy for non-small-cell lung cancer (NSCLC) is often controversial and strict accordance with ICRU requirements is hard to achieve. The Gross Tumour Volume (GTV) definition depends mainly on the imaging method used. We discuss the use of new imaging modalities, like PET, in GTV definition. The Clinical Target Volume (CTV) definition remains a separate, and still unresolved problem, especially in the part concerning the Elective Nodal Irradiation (ENI). Nowadays, there is no unified attitude among radiation oncologists regarding the necessity and extent of ENI. The common use of combined treatment modalities and the tendency to dose escalation, both increasing the potential toxicity, result in the more frequent use of involved-fields techniques. Problems relating to margins during Planning Target Volume (PTV) of lung cancer irradiation are also discussed. Another issue is the Interclinician variability in target volumes definition, especially when there is data indicating that the GTV, as defined by 3 D-treatment planning in NSCLC radiotherapy, may be highly prognostic for survival. We postulate that special attention should be paid to detailed precision of target volume determination in departmental and trial protocols. Careful analysis of patterns of failures from ongoing protocols will enable us to formulate the guidelines for target volume definition in radiotherapy for lung cancer. (author)

  16. Small-sized pump for the target chamber of the E-SUVI accelerator

    International Nuclear Information System (INIS)

    Borts, B.V.; Kravchenko, S.F.; Pisarev, G.V.; Rubashko, V.G.; Khorenko, V.K.

    1980-01-01

    The target chamber of the accelerator ESUVI is located at the high voltage end of the accelerating tube under the electrostatic generator conductor. The pumping out from the target chamber region has been performed through the accelerating tube its rate constituting 1.5 l/s which resulted in oxidation and contamination of the surface of irradiated targets in the course of the irradiation of chemically active materials. For obtaining high vacuum in a target chamber a small-size gettering-ionic pump of the ORBITRON type has been developed which operates in the autonomous mode. The pump pumping out rate in the pressure range 10 -5 -10 -7 mm Hg constitutes for air and nitrogen 20-25 l/s, ffor oxygen 30-40 l/s, for hydrogen 100-120 l/s. The pump weight without supply units is 2 kg. The pumps permits performing pressure indicator in the target chamber. Using the developed pump makes possible to decrease the target chamber pressure to 1x10 -6 mm Hg for active gases to 10 -8 -10 -9 mm Hg

  17. A study on repainting strategies for treating moderately moving targets with proton pencil beam scanning at the new Gantry 2 at PSI

    International Nuclear Information System (INIS)

    Zenklusen, S M; Pedroni, E; Meer, D

    2010-01-01

    Treating moving targets using a scanning gantry for proton therapy is a promising but very challenging, not yet clinically demonstrated treatment modality. The interference of organ motion with the sequence of the beam delivery produces uncontrolled dose inhomogeneities within the target. One promising approach to overcome this difficulty is to increase the speed of scanning in order to apply the dose repeatedly (so-called repainting). To obtain sufficiently high scanning speeds a new, technologically improved gantry-Gantry 2-has been designed and is currently under construction at PSI. As there are many possible repainting strategies, the way repainting will be implemented on Gantry 2 will depend on the result of a careful analysis of the various treatment delivery strategies available. To achieve this aim, and prior to the start of experimental work with Gantry 2, simulations of dose distribution errors due to organ motion under various beam delivery strategies were investigated. The effects of motion on the dose distribution were studied for moderate motion amplitudes (5 mm) for spherical target volumes in a homogeneous medium and with homogeneous dose. In total over 200 000 dose distributions have been simulated and analyzed and selected results are discussed. From the obtained results we are confident to be able to treat moderately moving targets on Gantry 2 using repainted pencil-beam spot scanning. Continuous line scanning seems to be the most elegant solution; it provides higher repainting rates and produces superior results but is probably more difficult to realize. For larger motion amplitudes, continuous line scanning still shows good results, but we plan anyways to use a gating system for these cases, not only to reduce the inhomogeneity within the target volume but also to reduce safety margins.

  18. Beam steering application for W-band data links with moving targets in 5G wireless networks

    DEFF Research Database (Denmark)

    Morales Vicente, Alvaro; Rodríguez Páez, Juan Sebastián; Gallardo, Omar

    2017-01-01

    to this problem, RoF (Radio-over-Fiber) architectures have been proposed as low-latency, cost-effective candidates. Two elements are introduced to extend the RoF approach. First, the carrier frequency is raised into the W-band (75–110 GHz) to increase the available capacity. Second, a mechanical beam......-steering solution based on a Stewart platform is adopted for the transmitter antenna to allow it to follow a moving receiver along a known path, thereby enhancing the coverage area. The performance of a system transmitting a 2.5 Gbit/s non-return-to-zero signal generated by photonic up-conversion over a wireless...

  19. Low-Altitude and Slow-Speed Small Target Detection Based on Spectrum Zoom Processing

    Directory of Open Access Journals (Sweden)

    Xuwang Zhang

    2018-01-01

    Full Text Available This paper proposes a spectrum zoom processing based target detection algorithm for detecting the weak echo of low-altitude and slow-speed small (LSS targets in heavy ground clutter environments, which can be used to retrofit the existing radar systems. With the existing range-Doppler frequency images, the proposed method firstly concatenates the data from the same Doppler frequency slot of different images and then applies the spectrum zoom processing. After performing the clutter suppression, the target detection can be finally implemented. Through the theoretical analysis and real data verification, it is shown that the proposed algorithm can obtain a preferable spectrum zoom result and improve the signal-to-clutter ratio (SCR with a very low computational load.

  20. psRNATarget: a plant small RNA target analysis server (2017 release).

    Science.gov (United States)

    Dai, Xinbin; Zhuang, Zhaohong; Zhao, Patrick Xuechun

    2018-04-30

    Plant regulatory small RNAs (sRNAs), which include most microRNAs (miRNAs) and a subset of small interfering RNAs (siRNAs), such as the phased siRNAs (phasiRNAs), play important roles in regulating gene expression. Although generated from genetically distinct biogenesis pathways, these regulatory sRNAs share the same mechanisms for post-translational gene silencing and translational inhibition. psRNATarget was developed to identify plant sRNA targets by (i) analyzing complementary matching between the sRNA sequence and target mRNA sequence using a predefined scoring schema and (ii) by evaluating target site accessibility. This update enhances its analytical performance by developing a new scoring schema that is capable of discovering miRNA-mRNA interactions at higher 'recall rates' without significantly increasing total prediction output. The scoring procedure is customizable for the users to search both canonical and non-canonical targets. This update also enables transmitting and analyzing 'big' data empowered by (a) the implementation of multi-threading chunked file uploading, which can be paused and resumed, using HTML5 APIs and (b) the allocation of significantly more computing nodes to its back-end Linux cluster. The updated psRNATarget server has clear, compelling and user-friendly interfaces that enhance user experiences and present data clearly and concisely. The psRNATarget is freely available at http://plantgrn.noble.org/psRNATarget/.

  1. Tensor Fukunaga-Koontz transform for small target detection in infrared images

    Science.gov (United States)

    Liu, Ruiming; Wang, Jingzhuo; Yang, Huizhen; Gong, Chenglong; Zhou, Yuanshen; Liu, Lipeng; Zhang, Zhen; Shen, Shuli

    2016-09-01

    Infrared small targets detection plays a crucial role in warning and tracking systems. Some novel methods based on pattern recognition technology catch much attention from researchers. However, those classic methods must reshape images into vectors with the high dimensionality. Moreover, vectorizing breaks the natural structure and correlations in the image data. Image representation based on tensor treats images as matrices and can hold the natural structure and correlation information. So tensor algorithms have better classification performance than vector algorithms. Fukunaga-Koontz transform is one of classification algorithms and it is a vector version method with the disadvantage of all vector algorithms. In this paper, we first extended the Fukunaga-Koontz transform into its tensor version, tensor Fukunaga-Koontz transform. Then we designed a method based on tensor Fukunaga-Koontz transform for detecting targets and used it to detect small targets in infrared images. The experimental results, comparison through signal-to-clutter, signal-to-clutter gain and background suppression factor, have validated the advantage of the target detection based on the tensor Fukunaga-Koontz transform over that based on the Fukunaga-Koontz transform.

  2. Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues.

    Science.gov (United States)

    Thomas, Mini; Kularatne, Sumith A; Qi, Longwu; Kleindl, Paul; Leamon, Christopher P; Hansen, Michael J; Low, Philip S

    2009-09-01

    Potential clinical applications of small interfering RNA (siRNA) are hampered primarily by delivery issues. We have successfully addressed the delivery problems associated with off-site targeting of highly toxic chemotherapeutic agents by attaching the drugs to tumor-specific ligands that will carry the attached cargo into the desired cancer cell. Indeed, several such tumor-targeted drugs are currently undergoing human clinical trials. We now show that efficient targeting of siRNA to malignant cells and tissues can be achieved by covalent conjugation of small-molecular-weight, high-affinity ligands, such as folic acid and DUPA (2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid), to siRNA. The former ligand binds a folate receptor that is overexpressed on a variety of cancers, whereas the latter ligand binds to prostate-specific membrane antigen that is overexpressed specifically on prostate cancers and the neovasculature of all solid tumors. Using these ligands, we show remarkable receptor-mediated targeting of siRNA to cancer tissues in vitro and in vivo.

  3. Targeted therapy for localized non-small-cell lung cancer: a review

    Directory of Open Access Journals (Sweden)

    Paleiron N

    2016-07-01

    Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

  4. Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Song X

    2017-10-01

    Full Text Available Xiao-li Song,1 Rui-jun Ju,2 Yao Xiao,1 Xin Wang,1 Shuang Liu,1 Min Fu,1 Jing-jing Liu,1 Li-yan Gu,1 Xue-tao Li,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 2Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, China Abstract: Chemotherapy for aggressive non-small-cell lung cancer (NSCLC usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC. Keywords: octreotide, honokiol, chemotherapy, vasculogenic mimicry, tumor metastasis, targeting drug delivery

  5. Development and application of a quantitative multiplexed small GTPase activity assay using targeted proteomics.

    Science.gov (United States)

    Zhang, Cheng-Cheng; Li, Ru; Jiang, Honghui; Lin, Shujun; Rogalski, Jason C; Liu, Kate; Kast, Juergen

    2015-02-06

    Small GTPases are a family of key signaling molecules that are ubiquitously expressed in various types of cells. Their activity is often analyzed by western blot, which is limited by its multiplexing capability, the quality of isoform-specific antibodies, and the accuracy of quantification. To overcome these issues, a quantitative multiplexed small GTPase activity assay has been developed. Using four different binding domains, this assay allows the binding of up to 12 active small GTPase isoforms simultaneously in a single experiment. To accurately quantify the closely related small GTPase isoforms, a targeted proteomic approach, i.e., selected/multiple reaction monitoring, was developed, and its functionality and reproducibility were validated. This assay was successfully applied to human platelets and revealed time-resolved coactivation of multiple small GTPase isoforms in response to agonists and differential activation of these isoforms in response to inhibitor treatment. This widely applicable approach can be used for signaling pathway studies and inhibitor screening in many cellular systems.

  6. Spiral CT of the pancreas. The value of small field-of-view targeted reconstruction

    International Nuclear Information System (INIS)

    Nishiharu, T.; Yamashita, Y.; Ogata, I.; Sumi, S.; Mitsuzaki, K.; Takahashi, M.

    1998-01-01

    Purpose: To compare the value of a retrospective targeted high-resolution spiral CT to the standard reconstruction technique in the assessment of pancreatic diseases. Material and methods: Spiral CT pancreatic images of a standard-size reconstruction protocol were compared prospectively with those of a retrospective targeted high-spatial-resolution reconstruction protocol in 30 patients. Prior to clinical evaluation, a phantom study was performed to evaluate the spatial resolution and signal-to-noise ratio of both protocols. Results: The high-resolution protocol achieved a good signal-to-noise ratio with acceptable spatial resolution. Phantom studies revealed increased image noise (+17%) with an increase in spatial resolution (+100%). In patients studied with the high-resolution protocol, the increase in noise was not significant but there was a marked improvement in the definition of small details. Conclusion: Images obtained with a targeted high-spatial-resolution reconstruction protocol showed superior lesion definition and vascular opacification compared with those obtained with a standard-size reconstruction protocol. This technique may have potential in the evaluation of small pancreatic abnormalities. (orig.)

  7. Phytophthora effector targets a novel component of small RNA pathway in plants to promote infection.

    Science.gov (United States)

    Qiao, Yongli; Shi, Jinxia; Zhai, Yi; Hou, Yingnan; Ma, Wenbo

    2015-05-05

    A broad range of parasites rely on the functions of effector proteins to subvert host immune response and facilitate disease development. The notorious Phytophthora pathogens evolved effectors with RNA silencing suppression activity to promote infection in plant hosts. Here we report that the Phytophthora Suppressor of RNA Silencing 1 (PSR1) can bind to an evolutionarily conserved nuclear protein containing the aspartate-glutamate-alanine-histidine-box RNA helicase domain in plants. This protein, designated PSR1-Interacting Protein 1 (PINP1), regulates the accumulation of both microRNAs and endogenous small interfering RNAs in Arabidopsis. A null mutation of PINP1 causes embryonic lethality, and silencing of PINP1 leads to developmental defects and hypersusceptibility to Phytophthora infection. These phenotypes are reminiscent of transgenic plants expressing PSR1, supporting PINP1 as a direct virulence target of PSR1. We further demonstrate that the localization of the Dicer-like 1 protein complex is impaired in the nucleus of PINP1-silenced or PSR1-expressing cells, indicating that PINP1 may facilitate small RNA processing by affecting the assembly of dicing complexes. A similar function of PINP1 homologous genes in development and immunity was also observed in Nicotiana benthamiana. These findings highlight PINP1 as a previously unidentified component of RNA silencing that regulates distinct classes of small RNAs in plants. Importantly, Phytophthora has evolved effectors to target PINP1 in order to promote infection.

  8. Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy.

    Science.gov (United States)

    Hengel, Sarah R; Spies, M Ashley; Spies, Maria

    2017-09-21

    To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents. The difficulty in capitalizing on synthetically lethal interactions in cancer cells is that many potential targets do not possess well-defined small-molecule binding determinates. In this review, we discuss several successful campaigns to identify and leverage small-molecule inhibitors of the DNA repair proteins, from PARP1, a paradigm case for clinically successful small-molecule inhibitors, to coveted new targets, such as RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease, and WRN DNA helicase. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Workflow for the Targeted and Untargeted Detection of Small Metabolites in Fish Skin Mucus

    Directory of Open Access Journals (Sweden)

    Lada Ivanova

    2018-06-01

    Full Text Available The skin mucus of fish is in permanent contact with the aquatic environment. Data from the analysis of the chemical composition of skin mucus could potentially be used for monitoring the health status of the fish. Knowledge about mucus composition or change in composition over time could also contribute to understanding the aetiology of certain diseases. The objective of the present study was the development of a workflow for non-invasive sampling of skin mucus from farmed salmon (Salmo salar for the targeted and untargeted detection of small metabolites. Skin mucus was either scraped off, wiped off using medical wipes, or the mucus’ water phase was absorbed using the same type of medical wipes that was used for the wiping method. Following a simple filtration step, the obtained mucus samples were subjected to hydrophilic interaction chromatography coupled to high-resolution mass spectrometry. Post-acquisition processing included the targeted analysis of 86 small metabolites, of which up to 60 were detected in absorbed mucus. Untargeted analysis of the mucus samples from equally treated salmon revealed that the total variation of the metabolome was lowest in absorbed mucus and highest in the scraped mucus. Thus, future studies including small-molecule metabolomics of skin mucus in fish would benefit from a sampling regime employing absorption of the water phase in order to minimize the bias related to the sampling step. Furthermore, the absorption method is also a less invasive approach allowing for repetitive sampling within short time intervals.

  10. A new type of liquid-3He target system using small mechanical refrigerators

    International Nuclear Information System (INIS)

    Kato, S.; Kobayashi, K.; Maruyama, K.; Okuno, H.; Konno, O.; Suda, T.; Maki, T.; Asami, H.; Koizumi, T.

    1991-04-01

    A new type of liquid- 3 He target has been developed for photoabsorption experiments at intermediate energies. Using the cooling power of liquid 4 He at reduced vapour pressure, 3 He gas is liquefied into a cylindrical target cell of 180 ml and is maintained at 2.0 K during the experiment. Evaporated 4 He gas is evacuated by a rotary pump and returned into the 4 He bath in the cryostat, where two small mechanical refrigerators with cooling capacities of 3 W at 4.3 K and 10 W at 20 K are operated for the purpose of 4 He recondensation. A maintenance-free operation of more than 1,000 hours has become possible by adopting the 4 He circulation system. (author)

  11. Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting.

    Science.gov (United States)

    Kwun, H J; Wendzicki, J A; Shuda, Y; Moore, P S; Chang, Y

    2017-12-07

    The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.

  12. Optimized computational imaging methods for small-target sensing in lens-free holographic microscopy

    Science.gov (United States)

    Xiong, Zhen; Engle, Isaiah; Garan, Jacob; Melzer, Jeffrey E.; McLeod, Euan

    2018-02-01

    Lens-free holographic microscopy is a promising diagnostic approach because it is cost-effective, compact, and suitable for point-of-care applications, while providing high resolution together with an ultra-large field-of-view. It has been applied to biomedical sensing, where larger targets like eukaryotic cells, bacteria, or viruses can be directly imaged without labels, and smaller targets like proteins or DNA strands can be detected via scattering labels like micro- or nano-spheres. Automated image processing routines can count objects and infer target concentrations. In these sensing applications, sensitivity and specificity are critically affected by image resolution and signal-to-noise ratio (SNR). Pixel super-resolution approaches have been shown to boost resolution and SNR by synthesizing a high-resolution image from multiple, partially redundant, low-resolution images. However, there are several computational methods that can be used to synthesize the high-resolution image, and previously, it has been unclear which methods work best for the particular case of small-particle sensing. Here, we quantify the SNR achieved in small-particle sensing using regularized gradient-descent optimization method, where the regularization is based on cardinal-neighbor differences, Bayer-pattern noise reduction, or sparsity in the image. In particular, we find that gradient-descent with sparsity-based regularization works best for small-particle sensing. These computational approaches were evaluated on images acquired using a lens-free microscope that we assembled from an off-the-shelf LED array and color image sensor. Compared to other lens-free imaging systems, our hardware integration, calibration, and sample preparation are particularly simple. We believe our results will help to enable the best performance in lens-free holographic sensing.

  13. A speeded-up saliency region-based contrast detection method for small targets

    Science.gov (United States)

    Li, Zhengjie; Zhang, Haiying; Bai, Jiaojiao; Zhou, Zhongjun; Zheng, Huihuang

    2018-04-01

    To cope with the rapid development of the real applications for infrared small targets, the researchers have tried their best to pursue more robust detection methods. At present, the contrast measure-based method has become a promising research branch. Following the framework, in this paper, a speeded-up contrast measure scheme is proposed based on the saliency detection and density clustering. First, the saliency region is segmented by saliency detection method, and then, the Multi-scale contrast calculation is carried out on it instead of traversing the whole image. Second, the target with a certain "integrity" property in spatial is exploited to distinguish the target from the isolated noises by density clustering. Finally, the targets are detected by a self-adaptation threshold. Compared with time-consuming MPCM (Multiscale Patch Contrast Map), the time cost of the speeded-up version is within a few seconds. Additional, due to the use of "clustering segmentation", the false alarm caused by heavy noises can be restrained to a lower level. The experiments show that our method has a satisfied FASR (False alarm suppression ratio) and real-time performance compared with the state-of-art algorithms no matter in cloudy sky or sea-sky background.

  14. Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2007-09-01

    Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

  15. Targeting Triple Negative Breast Cancer with a Small-sized Paramagnetic Nanoparticle

    Science.gov (United States)

    Zhang, Li; Varma, Nadimpalli RS; Gang, Zhang Z.; Ewing, James R.; Arbab, Ali S; Ali, Meser M

    2016-01-01

    There is no available targeted therapy or imaging agent for triple negative breast cancer (TNBC). We developed a small-sized dendrimer-based nanoparticle containing a clinical relevant MRI contrast agent, GdDOTA and a NIR fluorescent dye, DL680. Systemic delivery of dual-modal nanoparticles led to accumulation of the agents in a flank mouse model of TNBC that were detected by both optical and MR imaging. In-vivo fluorescence images, as well as ex-vivo fluorescence images of individual organs, demonstrated that nanoparticles accumulated into tumor selectively. A dual modal strategy resulted in a selective delivery of a small-sized (GdDOTA)42-G4-DL680 dendrimeric agent to TNBC tumors, avoiding other major organs. PMID:28018751

  16. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    International Nuclear Information System (INIS)

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-01-01

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife

  17. Efficient Isothermal Titration Calorimetry Technique Identifies Direct Interaction of Small Molecule Inhibitors with the Target Protein.

    Science.gov (United States)

    Gal, Maayan; Bloch, Itai; Shechter, Nelia; Romanenko, Olga; Shir, Ofer M

    2016-01-01

    Protein-protein interactions (PPI) play a critical role in regulating many cellular processes. Finding novel PPI inhibitors that interfere with specific binding of two proteins is considered a great challenge, mainly due to the complexity involved in characterizing multi-molecular systems and limited understanding of the physical principles governing PPIs. Here we show that the combination of virtual screening techniques, which are capable of filtering a large library of potential small molecule inhibitors, and a unique secondary screening by isothermal titration calorimetry, a label-free method capable of observing direct interactions, is an efficient tool for finding such an inhibitor. In this study we applied this strategy in a search for a small molecule capable of interfering with the interaction of the tumor-suppressor p53 and the E3-ligase MDM2. We virtually screened a library of 15 million small molecules that were filtered to a final set of 80 virtual hits. Our in vitro experimental assay, designed to validate the activity of mixtures of compounds by isothermal titration calorimetry, was used to identify an active molecule against MDM2. At the end of the process the small molecule (4S,7R)-4-(4-chlorophenyl)-5-hydroxy-2,7-dimethyl-N-(6-methylpyridin-2-yl)-4,6,7,8 tetrahydrIoquinoline-3-carboxamide was found to bind MDM2 with a dissociation constant of ~2 µM. Following the identification of this single bioactive compound, spectroscopic measurements were used to further characterize the interaction of the small molecule with the target protein. 2D NMR spectroscopy was used to map the binding region of the small molecule, and fluorescence polarization measurement confirmed that it indeed competes with p53.

  18. Feasibility study of multi-pass respiratory-gated helical tomotherapy of a moving target via binary MLC closure

    Science.gov (United States)

    Kim, Bryan; Chen, Jeff; Kron, Tomas; Battista, Jerry

    2010-11-01

    Gated radiotherapy of lung lesions is particularly complex for helical tomotherapy, due to the simultaneous motions of its three subsystems (gantry, couch and collimator). We propose a new way to implement gating for helical tomotherapy, namely multi-pass respiratory gating. In this method, gating is achieved by delivering only the beam projections that occur within a respiratory gating window, while blocking the rest of the beam projections by fully closing all collimator leaves. Due to the continuous couch motion, the planned beam projections must be delivered over multiple passes of radiation deliveries. After each pass, the patient couch is reset to its starting position, and the treatment recommences at a different phase of tumour motion to 'fill in' the previously blocked beam projections. The gating process may be repeated until the plan dose is delivered (full gating), or halted after a certain number of passes, with the entire remaining dose delivered in a final pass without gating (partial gating). The feasibility of the full gating approach was first tested for sinusoidal target motion, through experimental measurements with film and computer simulation. The optimal gating parameters for full and partial gating methods were then determined for various fractionation schemes through computer simulation, using a patient respiratory waveform. For sinusoidal motion, the PTV dose deviations of -29 to 5% observed without gating were reduced to range from -1 to 3% for a single fraction, with a 4 pass full gating. For a patient waveform, partial gating required fewer passes than full gating for all fractionation schemes. For a single fraction, the maximum allowed residual motion was only 4 mm, requiring large numbers of passes for both full (12) and partial (7 + 1) gating methods. The number of required passes decreased significantly for 3 and 30 fractions, allowing residual motion up to 7 mm. Overall, the multi-pass gating technique was shown to be a promising

  19. Feasibility study of multi-pass respiratory-gated helical tomotherapy of a moving target via binary MLC closure

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bryan; Chen, Jeff; Battista, Jerry [London Regional Cancer Program, London Health Sciences Centre, London, ON (Canada); Kron, Tomas, E-mail: bryan.kim@lhsc.on.c [Peter MacCallum Cancer Center, Melbourne (Australia)

    2010-11-21

    Gated radiotherapy of lung lesions is particularly complex for helical tomotherapy, due to the simultaneous motions of its three subsystems (gantry, couch and collimator). We propose a new way to implement gating for helical tomotherapy, namely multi-pass respiratory gating. In this method, gating is achieved by delivering only the beam projections that occur within a respiratory gating window, while blocking the rest of the beam projections by fully closing all collimator leaves. Due to the continuous couch motion, the planned beam projections must be delivered over multiple passes of radiation deliveries. After each pass, the patient couch is reset to its starting position, and the treatment recommences at a different phase of tumour motion to 'fill in' the previously blocked beam projections. The gating process may be repeated until the plan dose is delivered (full gating), or halted after a certain number of passes, with the entire remaining dose delivered in a final pass without gating (partial gating). The feasibility of the full gating approach was first tested for sinusoidal target motion, through experimental measurements with film and computer simulation. The optimal gating parameters for full and partial gating methods were then determined for various fractionation schemes through computer simulation, using a patient respiratory waveform. For sinusoidal motion, the PTV dose deviations of -29 to 5% observed without gating were reduced to range from -1 to 3% for a single fraction, with a 4 pass full gating. For a patient waveform, partial gating required fewer passes than full gating for all fractionation schemes. For a single fraction, the maximum allowed residual motion was only 4 mm, requiring large numbers of passes for both full (12) and partial (7 + 1) gating methods. The number of required passes decreased significantly for 3 and 30 fractions, allowing residual motion up to 7 mm. Overall, the multi-pass gating technique was shown to be a

  20. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A role for IGF-1R-targeted therapies in small-cell lung cancer?

    LENUS (Irish Health Repository)

    Gately, Kathy

    2012-02-01

    BACKGROUND: Small-cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. The insulin-like growth factor-1 receptor (IGF-1R) is an autocrine growth factor and an attractive therapeutic target in many solid tumors, but particularly in lung cancer. PATIENTS AND METHODS: This study examined tumor samples from 23 patients diagnosed with SCLC, 11 resected specimens and 12 nodal biopsies obtained by mediastinoscopy, for expression of IGF-1R using the monoclonal rabbit anti-IGF-1R (clone G11, Ventana Medical Systems, Tucson, AZ) and standard immunohistochemistry (IHC). RESULTS: All 23 tumor samples expressed IGF-1R with a range of stain intensity from weak (1+) to strong (3+). Ten tumors had a score of 3+, 7 tumors 2+, and 6 tumors 1+. Patient survival data were available for all 23 patients. Two patients died < 30 days post biopsy, therefore, the intensity of anti-IGF-1R immunostaining for 21 patients was correlated to survival. Patients with 3+ immunostaining had a poorer prognosis (P = .003). The overall survival of patients who underwent surgical resection was significantly better (median survival not reached) than patients who were not resected (median survival, 7.4 months) (P = .006). CONCLUSION: IGF-1R targeted therapies may have a role in the treatment of SCLC in combination with chemotherapy or as maintenance therapy. Further studies on the clinical benefit of targeting IGF-1R in SCLC are needed.

  2. Mycoplasma non-coding RNA: identification of small RNAs and targets

    Directory of Open Access Journals (Sweden)

    Franciele Maboni Siqueira

    2016-10-01

    Full Text Available Abstract Background Bacterial non-coding RNAs act by base-pairing as regulatory elements in crucial biological processes. We performed the identification of trans-encoded small RNAs (sRNA from the genomes of Mycoplama hyopneumoniae, Mycoplasma flocculare and Mycoplasma hyorhinis, which are Mycoplasma species that have been identified in the porcine respiratory system. Results A total of 47, 15 and 11 putative sRNAs were predicted in M. hyopneumoniae, M. flocculare and M. hyorhinis, respectively. A comparative genomic analysis revealed the presence of species or lineage specific sRNA candidates. Furthermore, the expression profile of some M. hyopneumoniae sRNAs was determined by a reverse transcription amplification approach, in three different culture conditions. All tested sRNAs were transcribed in at least one condition. A detailed investigation revealed a differential expression profile for two M. hyopneumoniae sRNAs in response to oxidative and heat shock stress conditions, suggesting that their expression is influenced by environmental signals. Moreover, we analyzed sRNA-mRNA hybrids and accessed putative target genes for the novel sRNA candidates. The majority of the sRNAs showed interaction with multiple target genes, some of which could be linked to pathogenesis and cell homeostasis activity. Conclusion This study contributes to our knowledge of Mycoplasma sRNAs and their response to environmental changes. Furthermore, the mRNA target prediction provides a perspective for the characterization and comprehension of the function of the sRNA regulatory mechanisms.

  3. WE-D-17A-04: Magnetically Focused Proton Irradiation of Small Volume Targets

    Energy Technology Data Exchange (ETDEWEB)

    McAuley, G; Slater, J [Loma Linda University, Loma Linda, CA (United States); Wroe, A [Loma Linda University Medical Center, Loma Linda, CA (United States)

    2014-06-15

    Purpose: To explore the advantages of magnetic focusing for small volume proton irradiations and the potential clinical benefits for radiosurgery targets. The primary goal is to create narrow elongated proton beams of elliptical cross section with superior dose delivery characteristics compared to current delivery modalities (eg, collimated beams). In addition, more general beam shapes are also under investigation. Methods: Two prototype magnets consisting of 24 segments of samarium-cobalt (Sm2Co17) permanent magnetic material adhered into hollow cylinders were manufactured for testing. A single focusing magnet was placed on a positioning track on our Gantry 1 treatment table and 15 mm diameter proton beams with energies and modulation relevant to clinical radiosurgery applications (127 to 186 MeV, and 0 to 30 mm modulation) were delivered to a terminal water tank. Beam dose distributions were measured using a PTW diode detector and Gafchromic EBT2 film. Longitudinal and transverse dose profiles were analyzed and compared to data from Monte Carlo simulations analogous to the experimental setup. Results: The narrow elongated focused beam spots showed high elliptical symmetry indicating high magnet quality. In addition, when compared to unfocused beams, peak-to-entrance depth dose ratios were 11 to 14% larger (depending on presence or extent of modulation), and minor axis penumbras were 11 to 20% smaller (again depending on modulation) for focused beams. These results suggest that the use of rare earth magnet assemblies is practical and could improve dose-sparing of normal tissue and organs at risk while delivering enhanced dose to small proton radiosurgery targets. Conclusion: Quadrapole rare earth magnetic assemblies are a promising and inexpensive method to counteract particle out scatter that tends to degrade the peak to entrance performance of small field proton beams. Knowledge gained from current experiments will inform the design of a prototype treatment

  4. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab

    Directory of Open Access Journals (Sweden)

    Chad A Reade

    2009-05-01

    Full Text Available Chad A Reade1, Apar Kishor Ganti1,21Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2Section of Oncology-Hematology, Department of internal Medicine, VA Medical Center, Omaha, NE, USAAbstract: Chemotherapy alone has limited ability to significantly improve survival in non-small lung cancer (NSCLC beyond what has already been achieved. The epidermal growth factor (EGF pathway plays a vital role in the pathogenesis and progression of NSCLC. Two classes of drugs inhibit the EGF receptor (EGFR pathway: small molecules that inhibit the intracellular tyrosine kinase activity of the receptor, and monoclonal antibodies that target the extracellular domain in the ligand-binding region. Cetuximab is a human – mouse chimeric immunoglobulin G1 class monoclonal antibody directed against EGFR. Preclinical studies with cetuximab suggested that there was inhibition of growth of human NSCLC cell lines. Cetuximab is currently the focus of intense investigation in various patient populations with NSCLC. This review focuses on clinical trials of cetuximab in NSCLC and identifies future directions with this agent.Keywords: non-small cell lung cancer, EGFR, cetuximab, monoclonal antibodies

  5. A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

    Science.gov (United States)

    Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

    2016-12-22

    In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy 1-3 . Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S 44 > S 60 > S 40 > S 29 ). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study 4 , we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

  6. Targeted therapies in development for non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Thanyanan Reungwetwattana

    2013-01-01

    Full Text Available The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by "druggable" protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC, the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2], RAS (rat sarcoma gene, BRAF (v-raf murine sarcoma viral oncogene homolog B1, MAPK (mitogen-activated protein kinase c-MET (c-mesenchymal-epithelial transition, FGFR (fibroblast growth factor receptor, DDR2 (discoidin domain receptor 2, PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha, PTEN (phosphatase and tensin homolog, AKT (protein kinase B, ALK (anaplastic lym phoma kinase, RET (rearranged during transfection, ROS1 (reactive oxygen species 1 and EPH (erythropoietin-producing hepatoma are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and

  7. Skin: Major target organ of allergic reactions to small molecular weight compounds

    International Nuclear Information System (INIS)

    Merk, Hans F.; Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller; Karlberg, Ann-Therese

    2007-01-01

    Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances

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

    Science.gov (United States)

    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)

  9. Small molecules, inhibitors of DNA-PK, targeting DNA repair and beyond

    Directory of Open Access Journals (Sweden)

    David eDavidson

    2013-01-01

    Full Text Available Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective in arresting tumor growth and reducing tumor burden, resistance and disease progression eventually occur. A major mechanism underlying this resistance is increased levels of cellular DNA repair. Most cells have complex mechanisms in place to repair DNA damage that occurs due to environmental exposures or normal metabolic processes. These systems, initially overwhelmed when faced with chemotherapy induced DNA damage, become more efficient under constant selective pressure and as a result chemotherapies become less effective. Thus, inhibiting DNA repair pathways using target specific small molecule inhibitors may overcome cellular resistance to DNA damaging chemotherapies. Non-homologous end joining (NHEJ a major mechanism for the repair of double strand breaks (DSB in DNA is regulated in part by the serine/threonine kinase, DNA dependent protein kinase (DNA-PK. The DNA-PK holoenzyme acts as a scaffold protein tethering broken DNA ends and recruiting other repair molecules. It also has enzymatic activity that may be involved in DNA damage signaling. Because of its’ central role in repair of DSBs, DNA-PK has been the focus of a number of small molecule studies. In these studies specific DNA-PK inhibitors have shown efficacy in synergizing chemotherapies in vitro. However, compounds currently known to specifically inhibit DNA-PK are limited by poor pharmacokinetics: these compounds have poor solubility and have high metabolic lability in vivo leading to short serum half-lives. Future improvement in DNA-PK inhibition will likely be achieved by designing new molecules based on the recently reported crystallographic structure of DNA

  10. Targeting the OB-Folds of Replication Protein A with Small Molecules

    Directory of Open Access Journals (Sweden)

    Victor J. Anciano Granadillo

    2010-01-01

    Full Text Available Replication protein A (RPA is the main eukaryotic single-strand (ss DNA-binding protein involved in DNA replication and repair. We have identified and developed two classes of small molecule inhibitors (SMIs that show in vitro inhibition of the RPA-DNA interaction. We present further characterization of these SMIs with respect to their target binding, mechanism of action, and specificity. Both reversible and irreversible modes of inhibition are observed for the different classes of SMIs with one class found to specifically interact with DNA-binding domains A and B (DBD-A/B of RPA. In comparison with other oligonucleotide/oligosaccharide binding-fold (OB-fold containing ssDNA-binding proteins, one class of SMIs displayed specificity for the RPA protein. Together these data demonstrate that the specific targeting of a protein-DNA interaction can be exploited towards interrogating the cellular activity of RPA as well as increasing the efficacy of DNA-damaging chemotherapeutics used in cancer treatment.

  11. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

    Science.gov (United States)

    Nagasaka, Misako; Gadgeel, Shirish M

    2018-01-01

    Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

  12. Target Therapy Using a Small Molecule Inhibitor against Angiogenic Receptors in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Peter Büchler

    2007-02-01

    Full Text Available PURPOSE: PD173074, a small molecule inhibitor of VEGF-RII and FGF-RI, targets neoangiogenesis and mitogenesis. This study aimed to analyze a singlecompound-driven inhibition of FGF and VEGF receptors in pancreatic cancer. EXPERIMENTAL DESIGN: RT-PCR and Western blots were performed to quantify protein expression and phosphorylation. Anchorage dependent and independent growth assays were used to study cell growth. With flow cytometry, cell cycle analysis and apoptosis were studied. In vivo HPAF-II and MIA PaCa-2 cells were xenografted. Animals were treated daily for 10 weeks. Immunohistochemistry was used to quantify microvessel density and apoptosis. RESULTS: Highest levels of FGF-RI were detectable in MIA PaCa-2 cells, lowest in HPAF-II cells. PD173074 inhibited cell growth most prominently in cells expressing high levels of FGF-RI. Cell cycle progression was inhibited by blocking transition in the G0/G1 phase, and consequently, apoptosis was increased. In vivo significant inhibition of orthotopic tumor growth was achieved by a combination effect of inhibition of mitogenesis, induction of apoptosis, and reduction of angiogenesis in PD173074-treated animals. CONCLUSIONS: These data highlight VEGF-RII and FGF-RI as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable pancreatic cancer patients.

  13. Small Interference RNA Targeting TLR4 Gene Effectively Attenuates Pulmonary Inflammation in a Rat Model

    Directory of Open Access Journals (Sweden)

    Feixiang Wu

    2012-01-01

    Full Text Available Objective. The present study was to investigate the feasibility of adenovirus-mediated small interference RNA (siRNA targeting Toll-like receptor 4 (TLR4 gene in ameliorating lipopolysaccharide- (LPS- induced acute lung injury (ALI. Methods. In vitro, alveolar macrophages (AMs were treated with Ad-siTLR4 and Ad-EFGP, respectively, for 12 h, 24 h, and 48 h, and then with LPS (100 ng/mL for 2 h, and the function and expression of TLR4 were evaluated. In vivo, rats received intratracheal injection of 300 μL of normal saline (control group, 300 μL of Ad-EGFP (Ad-EGFP group, or 300 μL of Ad-siTLR4 (Ad-siTLR4 group and then were intravenously treated with LPS (50 mg/kg to induce ALI. Results. Ad-siTLR4 treatment significantly reduced TLR4 expression and production of proinflammatory cytokines following LPS treatment both in vitro and in vivo. Significant alleviation of tissue edema, microvascular protein leakage, and neutrophil infiltration was observed in the AdsiTLR4-treated animals. Conclusion. TLR4 plays a critical role in LPS-induced ALI, and transfection of Ad-siTLR4 can effectively downregulate TLR4 expression in vitro and in vivo, accompanied by alleviation of LPS-induced lung injury. These findings suggest that TLR4 may serve as a potential target in the treatment of ALI and RNA interfering targeting TLR4 expression represents a therapeutic strategy.

  14. Evaluation of the interplay effect when using RapidArc to treat targets moving in the craniocaudal or right-left direction

    International Nuclear Information System (INIS)

    Court, Laurence; Wagar, Matthew; Berbeco, Ross; Reisner, Adam; Winey, Brian; Schofield, Debbie; Ionascu, Dan; Allen, Aaron M.; Popple, Richard; Lingos, Tania

    2010-01-01

    Purpose: We have investigated the dosimetric errors caused by the interplay between the motions of the LINAC and the tumor during the delivery of a volume modulated arc therapy treatment. This includes the development of an IMRT QA technique, applied here to evaluate RapidArc plans of varying complexity. Methods: An IMRT QA technique was developed, which involves taking a movie of the delivered dose (0.2 s frames) using a 2D ion chamber array. Each frame of the movie is then moved according to a respiratory trace and the cumulative dose calculated. The advantage of this approach is that the impact of turning the beam on at different points in the respiratory trace, and of different types of motion, can be evaluated using data from a single irradiation. We evaluated this technique by comparing with the results when we actually moved the phantom during irradiation. RapidArc plans were created to treat a 62 cc spherical tumor in a lung phantom (16 plans) and a 454 cc irregular tumor in an actual patient (five plans). The complexity of each field was controlled by adjusting the MU (312-966 MU). Each plan was delivered to a phantom, and a movie of the delivered dose taken using a 2D ion chamber array. Patient motion was modeled by shifting each dose frame according to a respiratory trace, starting the motion at different phases. The expected dose distribution was calculated by blurring the static dose distribution with the target motion. The dose error due to the interplay effect was then calculated by comparing the delivered dose with the expected dose distribution. Peak-to-peak motion of 0.5, 1.0, and 2.0 cm in the craniocaudal and right-left directions, with target periods of 3 and 5 s, were evaluated for each plan (252 different target motion/plan combinations). Results: The daily dose error due to the interplay effect was less than 10% for 98.4% of all pixels in the target for all plans investigated. The percentage of pixels for which the daily dose error could be

  15. Antibacterial small molecules targeting the conserved TOPRIM domain of DNA gyrase.

    Directory of Open Access Journals (Sweden)

    Scott S Walker

    Full Text Available To combat the threat of antibiotic-resistant Gram-negative bacteria, novel agents that circumvent established resistance mechanisms are urgently needed. Our approach was to focus first on identifying bioactive small molecules followed by chemical lead prioritization and target identification. Within this annotated library of bioactives, we identified a small molecule with activity against efflux-deficient Escherichia coli and other sensitized Gram-negatives. Further studies suggested that this compound inhibited DNA replication and selection for resistance identified mutations in a subunit of E. coli DNA gyrase, a type II topoisomerase. Our initial compound demonstrated weak inhibition of DNA gyrase activity while optimized compounds demonstrated significantly improved inhibition of E. coli and Pseudomonas aeruginosa DNA gyrase and caused cleaved complex stabilization, a hallmark of certain bactericidal DNA gyrase inhibitors. Amino acid substitutions conferring resistance to this new class of DNA gyrase inhibitors reside exclusively in the TOPRIM domain of GyrB and are not associated with resistance to the fluoroquinolones, suggesting a novel binding site for a gyrase inhibitor.

  16. Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist

    Science.gov (United States)

    Cao, Benjamin; Zhang, Zhen; Grassinger, Jochen; Williams, Brenda; Heazlewood, Chad K.; Churches, Quentin I.; James, Simon A.; Li, Songhui; Papayannopoulou, Thalia; Nilsson, Susan K.

    2016-01-01

    The inherent disadvantages of using granulocyte colony-stimulating factor (G-CSF) for hematopoietic stem cell (HSC) mobilization have driven efforts to identify alternate strategies based on single doses of small molecules. Here, we show targeting α9β1/α4β1 integrins with a single dose of a small molecule antagonist (BOP (N-(benzenesulfonyl)-L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine)) rapidly mobilizes long-term multi-lineage reconstituting HSC. Synergistic engraftment augmentation is observed when BOP is co-administered with AMD3100. Impressively, HSC in equal volumes of peripheral blood (PB) mobilized with this combination effectively out-competes PB mobilized with G-CSF. The enhanced mobilization observed using BOP and AMD3100 is recapitulated in a humanized NODSCIDIL2Rγ−/− model, demonstrated by a significant increase in PB CD34+ cells. Using a related fluorescent analogue of BOP (R-BC154), we show that this class of antagonists preferentially bind human and mouse HSC and progenitors via endogenously primed/activated α9β1/α4β1 within the endosteal niche. These results support using dual α9β1/α4β1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications. PMID:26975966

  17. Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

    Science.gov (United States)

    Price, Jeff; Molotoks, Amy; Warren, Rachel

    2018-01-01

    We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5–14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. PMID:29610386

  18. Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

    Science.gov (United States)

    Smith, Pete; Price, Jeff; Molotoks, Amy; Warren, Rachel; Malhi, Yadvinder

    2018-05-01

    We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5-14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  19. Information security : the moving target

    CSIR Research Space (South Africa)

    Dlamini, MT

    2009-01-01

    Full Text Available -product to an integral part of business operations (Conner and Coviello, 2004). This paper gives an overview of the following: � Where did information security come from? (the past) � How did it get to where it is today? (the present) � In what direction... operators were permitted to use these computers. Other users would submit their jobs to the operator through protected slots (batch processing). The key security issue during this era was ensuring that only the privileged computer operator (one user one...

  20. ERP – a moving target

    DEFF Research Database (Denmark)

    Koch, Christian

    2007-01-01

    Enterprise Resource Planning systems are central elements in longterm wide-ranging design and use networks. Present ERP research focuses on single-enterprise implementation and fails to address important features of the ERP networks such as multi-spatiality, the design of the generic and the dyna...

  1. A moving target--incorporating knowledge of the spatial ecology of fish into the assessment and management of freshwater fish populations.

    Science.gov (United States)

    Cooke, Steven J; Martins, Eduardo G; Struthers, Daniel P; Gutowsky, Lee F G; Power, Michael; Doka, Susan E; Dettmers, John M; Crook, David A; Lucas, Martyn C; Holbrook, Christopher M; Krueger, Charles C

    2016-04-01

    Freshwater fish move vertically and horizontally through the aquatic landscape for a variety of reasons, such as to find and exploit patchy resources or to locate essential habitats (e.g., for spawning). Inherent challenges exist with the assessment of fish populations because they are moving targets. We submit that quantifying and describing the spatial ecology of fish and their habitat is an important component of freshwater fishery assessment and management. With a growing number of tools available for studying the spatial ecology of fishes (e.g., telemetry, population genetics, hydroacoustics, otolith microchemistry, stable isotope analysis), new knowledge can now be generated and incorporated into biological assessment and fishery management. For example, knowing when, where, and how to deploy assessment gears is essential to inform, refine, or calibrate assessment protocols. Such information is also useful for quantifying or avoiding bycatch of imperiled species. Knowledge of habitat connectivity and usage can identify critically important migration corridors and habitats and can be used to improve our understanding of variables that influence spatial structuring of fish populations. Similarly, demographic processes are partly driven by the behavior of fish and mediated by environmental drivers. Information on these processes is critical to the development and application of realistic population dynamics models. Collectively, biological assessment, when informed by knowledge of spatial ecology, can provide managers with the ability to understand how and when fish and their habitats may be exposed to different threats. Naturally, this knowledge helps to better evaluate or develop strategies to protect the long-term viability of fishery production. Failure to understand the spatial ecology of fishes and to incorporate spatiotemporal data can bias population assessments and forecasts and potentially lead to ineffective or counterproductive management actions.

  2. Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

    Directory of Open Access Journals (Sweden)

    Jakobsen Maria

    2011-02-01

    Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

  3. SU-D-304-02: Magnetically Focused Proton Irradiation of Small Field Targets

    International Nuclear Information System (INIS)

    McAuley, GA; Slater, JM; Slater, JD; Wroe, AJ

    2015-01-01

    Purpose: To investigate the use of magnetic focusing for small field proton irradiations. It is hypothesized that magnetic focusing will provide significant dose distribution benefits over standard collimated beams for fields less than 10 mm diameter. Methods: Magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into hollow cylinders were designed and manufactured. Two focusing magnets were placed on a positioning track on our Gantry 1 treatment table. Proton beams with energies of 127 and 157 MeV, 15 and 30 mm modulation, and 8 mm initial diameters were delivered to a water tank using single-stage scattering. Depth dose distributions were measured using a PTW PR60020 diode detector and transverse profiles were measured with Gafchromic EBT3 film. Monte Carlo simulations were also performed - both for comparison with experimental data and to further explore the potential of magnetic focusing in silica. For example, beam spot areas (based on the 90% dose contour) were matched at Bragg depth between simulated 100 MeV collimated beams and simulated beams focused by two 400 T/m gradient magnets. Results: Preliminary experimental results show 23% higher peak to entrance dose ratios and flatter spread out Bragg peak plateaus for 8 mm focused beams compared with uncollimated beams. Monte Carlo simulations showed 21% larger peak to entrance ratios and a ∼9 fold more efficient dose to target delivery compared to spot-sized matched collimated beams. Our latest results will be presented. Conclusion: Our results suggest that rare earth focusing magnet assemblies could reduce skin dose and beam number while delivering dose to nominally spherical radiosurgery targets over a much shorter time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however expanded treatment sites can be also envisaged

  4. SU-D-304-02: Magnetically Focused Proton Irradiation of Small Field Targets

    Energy Technology Data Exchange (ETDEWEB)

    McAuley, GA; Slater, JM [Loma Linda University, Loma Linda, CA (United States); Slater, JD; Wroe, AJ [Loma Linda University Medical Center, Loma Linda, CA (United States)

    2015-06-15

    Purpose: To investigate the use of magnetic focusing for small field proton irradiations. It is hypothesized that magnetic focusing will provide significant dose distribution benefits over standard collimated beams for fields less than 10 mm diameter. Methods: Magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into hollow cylinders were designed and manufactured. Two focusing magnets were placed on a positioning track on our Gantry 1 treatment table. Proton beams with energies of 127 and 157 MeV, 15 and 30 mm modulation, and 8 mm initial diameters were delivered to a water tank using single-stage scattering. Depth dose distributions were measured using a PTW PR60020 diode detector and transverse profiles were measured with Gafchromic EBT3 film. Monte Carlo simulations were also performed - both for comparison with experimental data and to further explore the potential of magnetic focusing in silica. For example, beam spot areas (based on the 90% dose contour) were matched at Bragg depth between simulated 100 MeV collimated beams and simulated beams focused by two 400 T/m gradient magnets. Results: Preliminary experimental results show 23% higher peak to entrance dose ratios and flatter spread out Bragg peak plateaus for 8 mm focused beams compared with uncollimated beams. Monte Carlo simulations showed 21% larger peak to entrance ratios and a ∼9 fold more efficient dose to target delivery compared to spot-sized matched collimated beams. Our latest results will be presented. Conclusion: Our results suggest that rare earth focusing magnet assemblies could reduce skin dose and beam number while delivering dose to nominally spherical radiosurgery targets over a much shorter time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however expanded treatment sites can be also envisaged.

  5. Two Strategies for the Development of Mitochondrion-Targeted Small Molecule Radiation Damage Mitigators

    International Nuclear Information System (INIS)

    Rwigema, Jean-Claude M.; Beck, Barbara; Wang Wei; Doemling, Alexander; Epperly, Michael W.; Shields, Donna; Goff, Julie P.; Franicola, Darcy; Dixon, Tracy; Frantz, Marie-Celine; Wipf, Peter; Tyurina, Yulia; Kagan, Valerian E.; Wang, Hong

    2011-01-01

    Purpose: To evaluate the effectiveness of mitigation of acute ionizing radiation damage by mitochondrion-targeted small molecules. Methods and Materials: We evaluated the ability of nitroxide-linked alkene peptide isostere JP4-039, the nitric oxide synthase inhibitor-linked alkene peptide esostere MCF201-89, and the p53/mdm2/mdm4 protein complex inhibitor BEB55 to mitigate radiation effects by clonogenic survival curves with the murine hematopoietic progenitor cell line 32D cl 3 and the human bone marrow stromal (KM101) and pulmonary epithelial (IB3) cell lines. The p53-dependent mechanism of action was tested with p53 +/+ and p53 -/- murine bone marrow stromal cell lines. C57BL/6 NHsd female mice were injected i.p. with JP4-039, MCF201-89, or BEB55 individually or in combination, after receiving 9.5 Gy total body irradiation (TBI). Results: Each drug, JP4-039, MCF201-89, or BEB55, individually or as a mixture of all three compounds increased the survival of 32D cl 3 (p = 0.0021, p = 0.0011, p = 0.0038, and p = 0.0073, respectively) and IB3 cells (p = 0.0193, p = 0.0452, p = 0.0017, and p = 0.0019, respectively) significantly relative to that of control irradiated cells. KM101 cells were protected by individual drugs (p = 0.0007, p = 0.0235, p = 0.0044, respectively). JP4-039 and MCF201-89 increased irradiation survival of both p53 +/+ (p = 0.0396 and p = 0.0071, respectively) and p53 -/- cells (p = 0.0007 and p = 0.0188, respectively), while BEB55 was ineffective with p53 -/- cells. Drugs administered individually or as a mixtures of all three after TBI significantly increased mouse survival (p = 0.0234, 0.0009, 0.0052, and 0.0167, respectively). Conclusion: Mitochondrial targeting of small molecule radiation mitigators decreases irradiation-induced cell death in vitro and prolongs survival of lethally irradiated mice.

  6. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

    Directory of Open Access Journals (Sweden)

    Alison L McCormack

    Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

  7. Small Molecule Membrane Transporters in the Mammalian Podocyte: A Pathogenic and Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Cristina Zennaro

    2014-11-01

    Full Text Available The intriguingly complex glomerular podocyte has been a recent object of intense study. Researchers have sought to understand its role in the pathogenesis of common proteinuric diseases such as minimal change disease and focal segmental glomerular sclerosis. In particular, considerable effort has been directed towards the anatomic and functional barrier to macromolecular filtration provided by the secondary foot processes, but little attention has been paid to the potential of podocytes to handle plasma proteins beyond the specialization of the slit diaphragm. Renal membrane transporters in the proximal tubule have been extensively studied for decades, particularly in relation to drug metabolism and elimination. Recently, uptake and efflux transporters for small organic molecules have also been found in the glomerular podocyte, and we and others have found that these transporters can engage not only common pharmaceuticals but also injurious endogenous and exogenous agents. We have also found that the activity of podocyte transporters can be manipulated to inhibit pathogen uptake and efflux. It is conceivable that podocyte transporters may play a role in disease pathogenesis and may be a target for future drug development.

  8. Small, medium, large or supersize? The development and evaluation of interventions targeted at portion size

    Science.gov (United States)

    Vermeer, W M; Steenhuis, I H M; Poelman, M P

    2014-01-01

    In the past decades, portion sizes of high-caloric foods and drinks have increased and can be considered an important environmental obesogenic factor. This paper describes a research project in which the feasibility and effectiveness of environmental interventions targeted at portion size was evaluated. The studies that we conducted revealed that portion size labeling, offering a larger variety of portion sizes, and proportional pricing (that is, a comparable price per unit regardless of the size) were considered feasible to implement according to both consumers and point-of-purchase representatives. Studies into the effectiveness of these interventions demonstrated that the impact of portion size labeling on the (intended) consumption of soft drinks was, at most, modest. Furthermore, the introduction of smaller portion sizes of hot meals in worksite cafeterias in addition to the existing size stimulated a moderate number of consumers to replace their large meals by a small meal. Elaborating on these findings, we advocate further research into communication and marketing strategies related to portion size interventions; the development of environmental portion size interventions as well as educational interventions that improve people's ability to deal with a ‘super-sized' environment; the implementation of regulation with respect to portion size labeling, and the use of nudges to stimulate consumers to select healthier portion sizes. PMID:25033959

  9. Small D-type asteroids in the NEO population: new targets for space missions

    Science.gov (United States)

    Barucci, Maria Antonietta; Perna, D.; Popescu, M.; Fornasier, S.; Doressoundiram, A.; Lantz, C.; Merlin, F.; Fulchignoni, M.; Dotto, E.; Kanuchova, S.

    2018-06-01

    In the framework of the Near Earth Objects (NEOs) observational campaign carried out within the NEOShield-2 project, we identify nine new small D-type asteroids with estimated diameter less than 600 m. The link with meteorites for this class of asteroids is weak and the best fit obtained is with the Tagish Lake meteorite for seven of them. D-type asteroids are believed to contain the most pristine material of the Solar system and could have delivered the pre-biotic material to the Earth. Our results double the known sample of the D-types in the NEO population and triple the candidates of this class for a sample-return mission (at very low ΔV). Our finding increases considerably the number of targets for sample-return mission. A sample-return mission to a D-type asteroid will provide a major progress in understanding the early history of the Solar system and to investigate the origin of life on the Earth.

  10. Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

    Science.gov (United States)

    Childs-Disney, Jessica L; Disney, Matthew D

    2016-02-19

    Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5"-azido neomycin B and its FDA-approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics.

  11. A historical overview of protein kinases and their targeted small molecule inhibitors.

    Science.gov (United States)

    Roskoski, Robert

    2015-10-01

    catalytic subunits. PKA and all other protein kinase domains have a small amino-terminal lobe and large carboxyterminal lobe as determined by X-ray crystallography. The N-lobe and C-lobe form a cleft that serves as a docking site for MgATP. Nearly all active protein kinases contain a K/E/D/D signature sequence that plays important structural and catalytic roles. Protein kinases contain hydrophobic catalytic and regulatory spines and collateral shell residues that are required to assemble the active enzyme. There are two general kinds of conformational changes associated with most protein kinases. The first conformational change involves the formation of an intact regulatory spine to form an active enzyme. The second conformational change occurs in active kinases as they toggle between open and closed conformations during their catalytic cycles. Because mutations and dysregulation of protein kinases play causal roles in human disease, this family of enzymes has become one of the most important drug targets over the past two decades. Imatinib was approved by the United States FDA for the treatment of chronic myelogenous leukemia in 2001; this small molecule inhibits the BCR-Abl protein kinase oncoprotein that results from the formation of the Philadelphia chromosome. More than two dozen other orally effective mechanism-based small molecule protein kinase inhibitors have been subsequently approved by the FDA. These drugs bind to the ATP-binding site of their target enzymes and extend into nearby hydrophobic pockets. Most of these protein kinase inhibitors prolong survival in cancer patients only weeks or months longer than standard cytotoxic therapies. In contrast, the clinical effectiveness of imatinib against chronic myelogenous leukemia is vastly superior to that of any other targeted protein kinase inhibitor with overall survival lasting a decade or more. However, the near universal and expected development of drug resistance in the treatment of neoplastic disorders

  12. Optimum measurement and analysis of small polarization asymmetry in high-energy inelastic scattering using a polarized target

    International Nuclear Information System (INIS)

    Niinikoski, T.O.

    1976-01-01

    Optimum linear filter theory is employed for maximizing the signal-to-noise ratio in measurements of small polarization asymmetry in the presence of severe counting efficiency fluctuation, most likely to occur in high-energy inclusive and inelastic scattering experiments, using a polarized target. The r.m.s. error of the polarization asymmetry is obtained in closed form, allowing numeric optimization of the operation of the target. Guidelines are given for processing the record of data. (Auth.)

  13. Targeting MDM2 by the small molecule RITA: towards the development of new multi-target drugs against cancer

    Directory of Open Access Journals (Sweden)

    Espinoza-Fonseca L Michel

    2005-09-01

    Full Text Available Abstract Background The use of low-molecular-weight, non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Among these compounds, RITA (reactivation of p53 and induction of tumor cell apoptosis has been shown to be effective in the selective induction of apoptosis, and this effect is due to its binding to the p53 tumor suppressor. Since biological systems are highly dynamic and MDM2 may bind to different regions of p53, new alternatives should be explored. On this basis, the computational "blind docking" approach was employed in this study to see whether RITA would bind to MDM2. Results It was observed that RITA binds to the MDM2 p53 transactivation domain-binding cleft. Thus, RITA can be used as a lead compound for designing improved "multi-target" drugs. This novel strategy could provide enormous benefits to enable effective anti-cancer strategies. Conclusion This study has demonstrated that a single molecule can target at least two different proteins related to the same disease.

  14. Targeting Micrornas With Small Molecules: A Novel Approach to Treating Breast Cancer

    Science.gov (United States)

    2010-10-01

    DNAzyme, or deoxyribozyme, is a catalytic DNA that site-specifically cleaves the target RNA Watson – Crick base pairing to a complementary target...conserved antiparallel RNA A-helix fold among the selected pre- miRNA targets (Fig. 1a). Furthermore, 3D characteristics including Watson - Crick base pairs... Watson – Crick binding, leading to RNAse-H- mediated cleavage of the mRNA of the target gene. The ASOs also inhibit transcription, splicing, and

  15. Targeting the VEGF pathway: antiangiogenic strategies in the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Aita, Marianna; Fasola, Gianpiero; Defferrari, Carlotta; Brianti, Annalisa; Bello, Maria Giovanna Dal; Follador, Alessandro; Sinaccio, Graziella; Pronzato, Paolo; Grossi, Francesco

    2008-12-01

    The management of advanced non-small cell lung cancer (NSCLC) has evolved considerably in recent years, due to a progressive understanding of tumour biology and the identification of promising molecular targets. Several agents have been developed so far inhibiting vascular endothelial growth factor (VEGF) - a key protein in tumour neoangiogenesis, growth and dissemination - or its receptor signalling system. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab - a humanised anti-VEGF monoclonal antibody - over chemotherapy (CT) alone led the U.S. Food and Drug Administration (FDA) to approve the novel combination for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. In a randomised phase III trial presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival (PFS) compared to the standard arm. Based on these data, the European Medicines Agency (EMEA) has granted marketing authorisation for bevacizumab in addition to any platinum-based CT for first-line treatment of advanced NSCLC other than predominantly squamous histology. Aim of this report is to provide an overview on bevacizumab in NSCLC, with special emphasis on clinical results presented at ASCO last meeting. Multitargeted tyrosine kinase inhibitors (TKIs), sharing a focus on both the angiogenesis process and additional cell-surface receptors, and VEGF Trap, a novel fusion protein with markedly higher affinity for VEGF than bevacizumab, will be briefly discussed as well.

  16. Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Guowei ZHANG

    2017-04-01

    Full Text Available At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

  17. [Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

    Science.gov (United States)

    Zhang, Guowei; Wang, Huijuan; Ma, Zhiyong

    2017-04-20

    At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

  18. Moving target detection based on visual memory model and clustering%基于视觉记忆模型聚类的运动目标检测

    Institute of Scientific and Technical Information of China (English)

    陈容; 彭力

    2015-01-01

    In some gradient and repetitive motion modeling scenes, traditional Gaussian mixture background modeling has a good effect. But the algorithm needs a large amount of computation and storage space, and it can neither fit for complex background or background with sudden changes. To solve these problems, a new clustering background modeling based on human memory model is proposed. Combined with human memory model, the algorithm sets up a cluster model for each pixel, and each cluster can be adaptively created, updated and deleted according to background changes. The algorithm makes accurate judgments according to human ultra-short-term memory, short-term memory and long-term memory, and the moving target detection results can meet the judgment of the human sensory organs.%传统的混合高斯背景建模可对存在渐变及重复性运动的场景进行建模,但其运算过程需要足够的计算量和存储空间,不适应在复杂背景下的背景建模,也不能解决场景中存在的突变。针对这些问题,提出了一种基于记忆模型的聚类算法,算法为每个像素点设置一个聚类模型,每个聚类可根据背景的变化结合人类记忆模型自适应的创建、更新和删除。该算法通过人类瞬时记忆、短时记忆和长时记忆做出准确判断,运动目标检测结果更能符合人类感觉器官的判断。

  19. Discovering Small Molecule Inhibitors Targeted to Ligand-Stimulated RAGE-DIAPH1 Signaling Transduction

    Science.gov (United States)

    Pan, Jinhong

    The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of the RAGE cytoplasmic tail (ctRAGE) with intracellular effector, such as diaphanous 1 (DIAPH1), to initiate signal transduction cascades. ctRAGE is essential for RAGE-ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE is over-expressed in diseased tissues of most RAGE-associated pathogenic conditions, such as complications of Alzheimer's diseases, diabetes, vascular diseases, inflammation, cancers and neurodegeneration. They are the major diseases affecting a large population worldwide. RAGE can function as a biomarker or drug target for these diseases. The cytoplasmic tail of RAGE can be used as a drug target to inhibit RAGE-induced intracellular signaling by small molecule inhibitors to treat RAGE-associated diseases. We developed a high throughput screening assay with which we probed a small molecule library of 58,000 compounds to find that 777 small molecules displayed 50% inhibition and 97 compounds demonstrated dose-dependent inhibition of the binding of ctRAGE-DIAPH1. Eventually, there were 13 compounds which displayed dose-dependent inhibition of ctRAGE binding to DIAPH1 and direct binding to ctRAGE analyzed by 15N HSQC-NMR and native tryptophan fluorescence titration experiments; thus, they were

  20. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    International Nuclear Information System (INIS)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A.; Schoot, Agustinus J.A.J. van de; Buist, Marrije R.

    2018-01-01

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V 15Gy , V 30Gy , V 45Gy and D mean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V 15Gy , V 30Gy , V 45Gy and D mean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V 45Gy for bowel bag was >275 cm 3 and >200 cm 3 , respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [de

  1. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A. [Department of Human Oncology, University of Wisconsin-Madison, WI, 53792 (United States); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC 3002 (Australia) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Human Oncology, University of Wisconsin-Madison, WI 53792 (United States); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia) and Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Einstein Institute of Oncophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 (United States) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2012-08-15

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  2. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    International Nuclear Information System (INIS)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tomé, Wolfgang A.

    2012-01-01

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed “Super Sampling” involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  3. Single-Molecule View of Small RNA-Guided Target Search and Recognition.

    Science.gov (United States)

    Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

    2018-05-20

    Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

  4. Targeting the small airways with dry powder adenosine : A challenging concept

    NARCIS (Netherlands)

    van der Wiel, Erica; Lexmond, Anne J; van den Berge, Maarten; Postma, Dirkje S; Hagedoorn, Paul; Frijlink, Henderik W; Farenhorst, Martijn P; de Boer, Anne H; Ten Hacken, Nick H T

    2017-01-01

    Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment. Objective: We aimed to identify these patients by selectively

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

    Science.gov (United States)

    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.

  6. Production and dosimetric aspects of the potent Auger emitter Co-58m for targeted radionuclide therapy of small tumours

    DEFF Research Database (Denmark)

    Thisgaard, Helge; Elema, Dennis Ringkjøbing; Jensen, Mikael

    2011-01-01

    Based on theoretical calculations, the Auger emitter 58mCo has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state 58gCo is unfortunately unavoidable, as is ingrowth of the gr...

  7. Move up,Move out

    Institute of Scientific and Technical Information of China (English)

    Guo Yan

    2007-01-01

    @@ China has already become the world's largest manufacturer of cement,copper and steel.Chinese producers have moved onto the world stage and dominated the global consumer market from textiles to electronics with amazing speed and efficiency.

  8. Signal and data processing of small targets 1991; Proceedings of the Meeting, Orlando, FL, Apr. 1-3, 1991

    Science.gov (United States)

    Drummond, Oliver E.

    Attention is given to signal processing; track-before-detect; systems and simulations; association and filtering in tracking; and data processing. Particular attention is given to a linear modeling algorithm for tracking time-varying signals, an optoelectric Gabor detector for transient signals, small-target acquisition and typing by AASAP, model-based analysis of 3D spatial-temporal IR clutter suppression filtering, algorithms and architectures for implementing large-velocity filter banks, an end-to-end scenario-generating model for IRST performance analysis, detection and tracking of small targets in persistence, an incremental model for target maneuver estimation, implementation of an angle-only tracking filter, a global modeling approach for multisensor problems, passive-sensor data fusion, midcourse multitarget racking using continuous representation, neural data association, and statistical initial orbit determination. (For individual items see A93-26797 to A93-26799)

  9. Targeting MicroRNAs with Small Molecules a Novel Approach to Treating Breast Cancer

    Science.gov (United States)

    2011-10-01

    or deoxyribozyme, is a catalytic DNA that site-specifically cleaves the target RNA Watson – Crick base pairing to a complementary target sequence...RNA A-helix fold among the selected pre- miRNA targets. Furthermore, 3D characteristics including Watson - Crick base pairs and wobble base pairs...phosphorothioate backbone in addition to 2′-O-methoxyethyl AMOs are ASOs against miRNAs and therefore produce ASO–miRNA duplexes through Watson – Crick binding

  10. Modern Estimation Techniques and Optimal Maneuver Targeting for Autonomous Optical Navigation around Small Bodies

    Data.gov (United States)

    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...

  11. Penetration of a Small Caliber Projectile into Single and Multi-layered Targets

    Directory of Open Access Journals (Sweden)

    Riad A.M.

    2010-06-01

    Full Text Available The normal penetration of armor-piercing projectiles into single and multi-layered steel plates has been investigated. An experimental program has been conducted to study the effect of spaced and in-contact layered targets on their ballistic resistance. Armor piercing projectiles with caliber of 7.62 mm were fired against a series of single and multi-layered steel targets. The projectile impact velocities were ranged from 300-600 m/s, whereas the total thicknesses of the tested single, spaced and in-contact layered steel targets were 3 mm. The penetration process of different tested target configurations has been simulated using Autodayn-2D hydrocode. The experimental measurements of the present work were used to discuss the effect of impact velocity, target configurations and number of layers of different spaced and in-contact layered steel targets on their ballistic resistance. In addition, the post-firing examination of the tested targets over the used impact velocity range showed that the single and each layer of spaced and in-contact laminated steel targets were failed by petalling. Finally, the obtained experimental measurements were compared with the corresponding numerical results of Autodyn-2D hydrocode, good agreement was generally obtained.

  12. Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

    Science.gov (United States)

    Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

    2017-09-26

    Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

  13. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xiaonan [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Yang Chunying [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Liu Hai; Wang Qi [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Wu Shixiu [Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou (China); Li Xia; Xie Tian [Research Center of Biomedicine and Health, Hangzhou Normal University, Hangzhou (China); Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Xu Bo, E-mail: bxu@tmhs.org [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Zheng, Shu, E-mail: zhengshu@zju.edu.cn [Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

    2012-12-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged {gamma}-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  14. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    International Nuclear Information System (INIS)

    Sun Xiaonan; Yang Chunying; Liu Hai; Wang Qi; Wu Shixiu; Li Xia; Xie Tian; Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian; Xu Bo; Zheng, Shu

    2012-01-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged γ-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  15. A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

    Science.gov (United States)

    Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

    2016-03-14

    The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

  16. MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Minxia Liu

    2016-09-01

    Full Text Available MicroRNAs (miRNAs have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

  17. MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Liu, Minxia; Zhou, Kecheng; Cao, Yi

    2016-09-26

    MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

  18. Identification of novel small-molecule Ulex europaeus I mimetics for targeted drug delivery.

    Science.gov (United States)

    Hamashin, Christa; Spindler, Lisa; Russell, Shannon; Schink, Amy; Lambkin, Imelda; O'Mahony, Daniel; Houghten, Richard; Pinilla, Clemencia

    2003-11-17

    Lectin mimetics have been identified that may have potential application towards targeted drug delivery. Synthetic multivalent polygalloyl constructs effectively competed with Ulex europaeus agglutinin I (UEA1) for binding to intestinal Caco-2 cell membranes.

  19. Mitochondria: 3-bromopyruvate vs. mitochondria? A small molecule that attacks tumors by targeting their bioenergetic diversity.

    Science.gov (United States)

    Galina, Antonio

    2014-09-01

    Enhanced glycolysis, the classic bioenergetic phenotype of cancer cells was described by Otto Warburg approximately 90 years ago. However, the Warburg hypothesis does not necessarily imply mitochondrial dysfunction. The alkyl-halogen, 3-bromopyruvate (3BP), would not be expected to have selective targets for cancer therapy due to its high potential reactivity toward many SH side groups. Contrary to predictions, 3BP interferes with glycolysis and oxidative phosphorylation in cancer cells without side effects in normal tissues. The mitochondrial hexokinase II has been claimed as the main target. This "Organelle in focus" article presents a historical view of the use of 3BP in biochemistry and its effects on ATP-producing pathways of cancer cells. I will discuss how the alkylated enzymes contribute to the cooperative collapse of mitochondria and apoptosis. Perspectives for targeting 3BP to bioenergetics enzymes for cancer treatment will be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Control of Target Molecular Recognition in a Small Pore Space with Biomolecule-Recognition Gating Membrane.

    Science.gov (United States)

    Okuyama, Hiroto; Oshiba, Yuhei; Ohashi, Hidenori; Yamaguchi, Takeo

    2018-05-01

    A biomolecule-recognition gating membrane, which introduces thermosensitive graft polymer including molecular recognition receptor into porous membrane substrate, can close its pores by recognizing target biomolecule. The present study reports strategies for improving both versatility and sensitivity of the gating membrane. First, the membrane is fabricated by introducing the receptor via a selectively reactive click reaction improving the versatility. Second, the sensitivity of the membrane is enhanced via an active delivering method of the target molecules into the pores. In the method, the tiny signal of the target biomolecule is amplified as obvious pressure change. Furthermore, this offers 15 times higher sensitivity compared to the previously reported passive delivering method (membrane immersion to sample solution) with significantly shorter recognition time. The improvement will aid in applying the gating membrane to membrane sensors in medical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Small molecules targeting LapB protein prevent Listeria attachment to catfish muscle.

    Directory of Open Access Journals (Sweden)

    Ali Akgul

    Full Text Available Listeria monocytogenes is a Gram-positive foodborne pathogen and the causative agent of listeriosis. L. monocytogenes lapB gene encodes a cell wall surface anchor protein, and mutation of this gene causes Listeria attenuation in mice. In this work, the potential role of Listeria LapB protein in catfish fillet attachment was investigated. To achieve this, boron-based small molecules designed to interfere with the active site of the L. monocytogenes LapB protein were developed, and their ability to prevent L. monocytogenes attachment to fish fillet was tested. Results indicated that seven out of nine different small molecules were effective in reducing the Listeria attachment to catfish fillets. Of these, three small molecules (SM3, SM5, and SM7 were highly effective in blocking Listeria attachment to catfish fillets. This study suggests an alternative strategy for reduction of L. monocytogenes contamination in fresh and frozen fish products.

  2. De-repressing LncRNA-Targeted Genes to Upregulate Gene Expression: Focus on Small Molecule Therapeutics

    Directory of Open Access Journals (Sweden)

    Roya Pedram Fatemi

    2014-01-01

    Full Text Available Non-protein coding RNAs (ncRNAs make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an important role in normal development and their expression levels are dysregulated in several diseases. Recently, several long noncoding RNAs (lncRNAs have been shown to alter the epigenetic status of genomic loci and suppress the expression of target genes. This review will present examples of such a mechanism and focus on the potential to target lncRNAs for achieving therapeutic gene upregulation by de-repressing genes that are epigenetically silenced in various diseases. Finally, the potential to target lncRNAs, through their interactions with epigenetic enzymes, using various tools, such as small molecules, viral vectors and antisense oligonucleotides, will be discussed. We suggest that small molecule modulators of a novel class of drug targets, lncRNA-protein interactions, have great potential to treat some cancers, cardiovascular disease, and neurological disorders.

  3. Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia.

    Science.gov (United States)

    Kojima, Kenji K; Jurka, Jerzy

    2015-01-01

    Most non-long terminal repeat (non-LTR) retrotransposons encoding a restriction-like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an "archaeal" RNase H domain upstream of reverse transcriptase (RT), which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes.

  4. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

    NARCIS (Netherlands)

    Zak, Krzysztof M.; Grudnik, Przemyslaw; Guzik, Katarzyna; Zieba, Bartosz J.; Musielak, Bogdan; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

    2016-01-01

    Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first

  5. Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

    International Nuclear Information System (INIS)

    Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I.; Barik, Tapan Kumar

    2012-01-01

    COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

  6. Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I., E-mail: prem_indra@yahoo.co.in [Radiation Biosciences Division, Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Barik, Tapan Kumar [P.G. Department of Zoology, Berhampur University, Berhampur (India)

    2012-07-01

    COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

  7. A semantic web ontology for small molecules and their biological targets.

    Science.gov (United States)

    Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

    2010-05-24

    A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

  8. Small RNA target genes and regulatory connections in the Vibrio cholerae quorum sensing system

    DEFF Research Database (Denmark)

    Hammer, Brian K; Svenningsen, Sine Lo

    2011-01-01

    of extracellular autoinducers triggers a signaling cascade resulting in the transcription of four small regulatory RNAs (sRNAs). Our results support the model that the QS sRNAs bind to the 5' untranslated region of multiple mRNAs and alter the fate of one in a positive manner and several others in a negative...

  9. Low-energy electron emitters for targeted radiotherapy of small tumours

    International Nuclear Information System (INIS)

    Bernhardt, Peter; Forssell-Aronsson, Eva; Jacobsson, Lars; Skarnemark, Gunnar

    2001-01-01

    The possibility of using electron emitters to cure a cancer with metastatic spread depends on the energy of the emitted electrons. Electrons with high energy will give a high, absorbed dose to large tumours, but the absorbed dose to small tumours or single tumour cells will be low, because the range of the electrons is too long. The fraction of energy absorbed within the tumour decreases with increasing electron energy and decreasing tumour size. For tumours smaller than 1 g, the tumour-to-normal-tissue mean absorbed dose-rate ratio, TND, will be low, e.g. for 131 I and 90 Y, because of the high energy of the emitted electrons. For radiotherapy of small tumours, radionuclides emitting charged particles with short ranges (a few m u m ) are required. A mathematical model was constructed to evaluate the relation between TND and electron energy, photon-to-electron energy ratio, p/e, and tumour size. Criteria for the selection of suitable radionuclides for the treatment of small tumours were defined based on the results of the TND model. In addition, the possibility of producing such radionuclides and their physical and chemical properties were evaluated. Based on the mathematical model, the energy of the emitted electrons should be = 40 keV for small tumours ( 58m Co, 103m Rh, 119 Sb, 161 Ho, and 189m Os. All of these nuclides by internal transition or electron capture, which yields conversion and Auger electrons, and it should be possible to produce most of them in therapeutic amounts. The five low-energy electron-emitting radionuclides identified may be relevant in the radiation treatment of small tumours, especially if bound to internalizing radiopharmaceuticals

  10. Small-molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma.

    Science.gov (United States)

    Boro, Aleksandar; Prêtre, Kathya; Rechfeld, Florian; Thalhammer, Verena; Oesch, Susanne; Wachtel, Marco; Schäfer, Beat W; Niggli, Felix K

    2012-11-01

    Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well-characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read-out system, we screened a small-molecule compound library enriched for FDA-approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit-list of nine well-known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes. Copyright © 2012 UICC.

  11. Moving toroidal limiter

    International Nuclear Information System (INIS)

    Ikuta, Kazunari; Miyahara, Akira.

    1983-06-01

    The concept of the limiter-divertor proposed by Mirnov is extended to a toroidal limiter-divertor (which we call moving toroidal limiter) using the stream of ferromagnetic balls coated with a low Z materials such as plastics, graphite and ceramics. An important advantage of the use of the ferromagnetic materials would be possible soft landing of the balls on a catcher, provided that the temperature of the balls is below Curie point. Moreover, moving toroidal limiter would work as a protector of the first wall not only against the vertical movement of plasma ring but also against the violent inward motion driven by major disruption because the orbit of the ball in the case of moving toroidal limiter distributes over the small major radius side of the toroidal plasma. (author)

  12. Space micropropulsion systems for Cubesats and small satellites: From proximate targets to furthermost frontiers

    Science.gov (United States)

    Levchenko, Igor; Bazaka, Kateryna; Ding, Yongjie; Raitses, Yevgeny; Mazouffre, Stéphane; Henning, Torsten; Klar, Peter J.; Shinohara, Shunjiro; Schein, Jochen; Garrigues, Laurent; Kim, Minkwan; Lev, Dan; Taccogna, Francesco; Boswell, Rod W.; Charles, Christine; Koizumi, Hiroyuki; Shen, Yan; Scharlemann, Carsten; Keidar, Michael; Xu, Shuyan

    2018-03-01

    Rapid evolution of miniaturized, automatic, robotized, function-centered devices has redefined space technology, bringing closer the realization of most ambitious interplanetary missions and intense near-Earth space exploration. Small unmanned satellites and probes are now being launched in hundreds at a time, resurrecting a dream of satellite constellations, i.e., wide, all-covering networks of small satellites capable of forming universal multifunctional, intelligent platforms for global communication, navigation, ubiquitous data mining, Earth observation, and many other functions, which was once doomed by the extraordinary cost of such systems. The ingression of novel nanostructured materials provided a solid base that enabled the advancement of these affordable systems in aspects of power, instrumentation, and communication. However, absence of efficient and reliable thrust systems with the capacity to support precise maneuvering of small satellites and CubeSats over long periods of deployment remains a real stumbling block both for the deployment of large satellite systems and for further exploration of deep space using a new generation of spacecraft. The last few years have seen tremendous global efforts to develop various miniaturized space thrusters, with great success stories. Yet, there are critical challenges that still face the space technology. These have been outlined at an inaugural International Workshop on Micropropulsion and Cubesats, MPCS-2017, a joint effort between Plasma Sources and Application Centre/Space Propulsion Centre (Singapore) and the Micropropulsion and Nanotechnology Lab, the G. Washington University (USA) devoted to miniaturized space propulsion systems, and hosted by CNR-Nanotec—P.Las.M.I. lab in Bari, Italy. This focused review aims to highlight the most promising developments reported at MPCS-2017 by leading world-reputed experts in miniaturized space propulsion systems. Recent advances in several major types of small

  13. CRISPR Approaches to Small Molecule Target Identification. | Office of Cancer Genomics

    Science.gov (United States)

    A long-standing challenge in drug development is the identification of the mechanisms of action of small molecules with therapeutic potential. A number of methods have been developed to address this challenge, each with inherent strengths and limitations. We here provide a brief review of these methods with a focus on chemical-genetic methods that are based on systematically profiling the effects of genetic perturbations on drug sensitivity.

  14. Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.

    Science.gov (United States)

    Burns, Michael C; Sun, Qi; Daniels, R Nathan; Camper, DeMarco; Kennedy, J Phillip; Phan, Jason; Olejniczak, Edward T; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

    2014-03-04

    Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

  15. Targeted histology sampling from atypical small acinar proliferation area detected by repeat transrectal prostate biopsy

    Directory of Open Access Journals (Sweden)

    A. V. Karman

    2017-01-01

    Full Text Available Оbjective: to define the approach to the management of patients with the detected ASAP area.Materials and methods. In the time period from 2012 through 2015, 494 patients with previously negative biopsy and remaining suspicion of prostate cancer (PCa were examined. The patients underwent repeat 24-core multifocal prostate biopsy with taking additional tissue samples from suspicious areas detected by multiparametric magnetic resonance imaging and transrectal ultrasound. An isolated ASAP area was found in 127 (25. 7 % of the 494 examined men. All of them were offered to perform repeat target transrectal biopsy of this area. Targeted transrectal ultrasound guided biopsy of the ASAP area was performed in 56 (44.1 % of the 127 patients, 53 of them being included in the final analysis.Results. PCa was diagnosed in 14 (26.4 % of the 53 patients, their mean age being 64.4 ± 6.9 years. The average level of prostate-specific antigen (PSA in PCa patients was 6.8 ± 3.0 ng/ml, in those with benign lesions – 9.3 ± 6.5 ng/ml; the percentage ratio of free/total PSA with PCa was 16.2 ± 7,8 %, with benign lesions – 23.3 ± 7.7 %; PSA density in PCa patients was 0.14 ± 0.07 ng/ml/cm3, in those with benign lesions – 0.15 ± 0.12 ng/ml/cm3. Therefore, with ASAP area being detected in repeat prostate biopsy samples, it is advisable that targeted extended biopsy of this area be performed. 

  16. Targeting of Streptococcus mutans Biofilms by a Novel Small Molecule Prevents Dental Caries and Preserves the Oral Microbiome.

    Science.gov (United States)

    Garcia, S S; Blackledge, M S; Michalek, S; Su, L; Ptacek, T; Eipers, P; Morrow, C; Lefkowitz, E J; Melander, C; Wu, H

    2017-07-01

    Dental caries is a costly and prevalent disease characterized by the demineralization of the tooth's enamel. Disease outcome is influenced by host factors, dietary intake, cariogenic bacteria, and other microbes. The cariogenic bacterial species Streptococcus mutans metabolizes sucrose to initiate biofilm formation on the tooth surface and consequently produces lactic acid to degrade the tooth's enamel. Persistence of S. mutans biofilms in the oral cavity can lead to tooth decay. To date, no anticaries therapies that specifically target S. mutans biofilms but do not disturb the overall oral microbiome are available. We screened a library of 2-aminoimidazole antibiofilm compounds with a biofilm dispersion assay and identified a small molecule that specifically targets S. mutans biofilms. At 5 µM, the small molecule annotated 3F1 dispersed 50% of the established S. mutans biofilm but did not disperse biofilms formed by the commensal species Streptococcus sanguinis or Streptococcus gordonii. 3F1 dispersed S. mutans biofilms independently of biofilm-related factors such as antigen I/II and glucosyltransferases. 3F1 treatment effectively prevented dental caries by controlling S. mutans in a rat caries model without perturbing the oral microbiota. Our study demonstrates that selective targeting of S. mutans biofilms by 3F1 was able to effectively reduce dental caries in vivo without affecting the overall oral microbiota shaped by the intake of dietary sugars, suggesting that the pathogenic biofilm-specific treatment is a viable strategy for disease prevention.

  17. A Small Molecule that Targets r(CGG)exp and Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome

    Science.gov (United States)

    Disney, Matthew D.; Liu, Biao; Yang, Wang-Yong; Sellier, Chantal; Tran, Tuan; Charlet-Berguerand, Nicolas; Childs-Disney, Jessica L.

    2012-01-01

    The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is a lack of knowledge of the chemical and RNA motif spaces that interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)exp , that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5’CGG/3’GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp -protein complex in vitro. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition to r(CGG)exp . Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp -protein aggregates. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)exp promotes toxicity. PMID:22948243

  18. What extent will small-scale laser-beam fluctuations seed the Rayleigh-Taylor instability in direct-drive targets

    International Nuclear Information System (INIS)

    Skupsky, S.; McCrory, R.L.; Verdon, C.P.

    1984-01-01

    The nonuniformity in laser energy deposition on a spherical target is calculated for multiple overlapping beams having small-scale fluctuations. Such nonuniformities can imprint themselves on the target surface and ''seed'' the Rayleigh-Taylor instability early in the pulse before an adequate, smoothing plasma-atmosphere has been established. The resulting growth of target deformation during the implosion is estimated

  19. Investigation of magnetic nanoparticle targeting in a simplified model of small vessel aneurysm

    Energy Technology Data Exchange (ETDEWEB)

    Mirzababaei, S.N. [Department of Chemical Engineering, Noshirvani Babol University of Technology, Babol (Iran, Islamic Republic of); Gorji, Tahereh B., E-mail: gorji.tahereh@stu.nit.ac.ir [Department of Mechanical Engineering, Noshirvani Babol University of Technology, Babol (Iran, Islamic Republic of); Baou, M.; Gorji-Bandpy, M. [Department of Mechanical Engineering, Noshirvani Babol University of Technology, Babol (Iran, Islamic Republic of); Fatouraee, Nasser [Department of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

    2017-03-15

    An in simulacra study was conducted to investigate the capture efficiency (CE) of magnetic nanoparticles (MNPs) in aneurysm model, under the effect of a bipolar permanent magnetic system positioned at the vicinity of the model vessel. The bipolar magnetic system with an active space of 9 cm was designed by FEMM software. The MNPs were magnetite nanoparticles synthesized by the hydrothermal method which were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscope and magnetometer measurements. Ferrofluid velocity, magnetic field strength, and aneurysm volume all proved to be important parameters which affect the capturing of MNPs. Overall, the results of this in simulacra study confirmed the effectiveness of magnetic targeting for possible aneurysm embolization. - Highlights: • An in simulacra investigation of the magnetic targeting in mechanical aneurysm embolization was conducted. • A bipolar permanent magnetic system with an active space of 9 cm was designed by FEMM software. • Magnetic nanofluid was synthetized and applied in an experimental setup to study the effect of different flow, magnetic field and geometry parameters on the capture efficiency of the magnetic particles acting as a dug carrier agent.

  20. Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications.

    Science.gov (United States)

    Li, Junjie; Oyen, Raymond; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely (131)I-hypericin ((131)I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

  1. [Current Status and Development of Traditional Chemotherapy in Non-small Cell Lung Cancer under the Background of Targeted Therapy].

    Science.gov (United States)

    Zhang, Guowei; Wang, Huijuan; Zhang, Mina; Li, Peng; Ma, Zhiyong

    2015-09-20

    In recent years, along with rapid development of targeted therapy in non-small cell lung cancer, traditional chemotherapy get less and less attention. Yet it still can not be ignored in the current that how to locate and use traditional chemotherapy so patients could derive maximum benefit. For this purpose, through the literature review and analysis, we point out there are still many traditional chemotherapy irreplaceable places whatever patients' driver gene status. And there are some new treatment modalities of traditional chemotherapy which have been developed to further improve patients' survival. At the same time, through exposition of predictive bio-markers development in chemotherapy, we pointed out that the future of traditional chemotherapy must be part of "targeted therapy".

  2. PV, Wind and Storage Integration on Small Islands for the Fulfilment of the 50-50 Renewable Electricity Generation Target

    Directory of Open Access Journals (Sweden)

    Javier Mendoza-Vizcaino

    2017-05-01

    Full Text Available Decarbonisation in the generation of electricity is necessary to reduce fossil fuel consumption, the pollution emitted and to meet the Energy Technology Perspectives 2 ° C Scenario (2DS targets. Small islands are not exempt from this target, so this study’s emphasis is placed on a 50-50 target: to reduce the fossil fuel consumption through electricity generation from Renewable Energy Sources (RES to cover 50% of all electric demand by 2050 on small islands. Using Cozumel Island, Mexico, as a case study, this analysis will be based on three factors: economical, technical, and land-use possibilities of integrating Renewable Energy Technologies (RETs into the existing electrical grid. This analysis is made through long-term statistical models. A deterministic methodology is used to perform time-series simulations. The selection of the best system was made on the basis of a Dimensional Statistical Variable (DSV through primary and secondary category rankings. The presented methodology determines the best systems for capturing the initial capital cost and competitiveness of this new proposal compared with the current system of electricity generation on the Island, and can be applied to small islands as well. According to the results, all systems proposed are able to completely satisfy the renewable electricity needed by 2050 in all scenarios. From the 12 system proposals that were compared, two systems, System 2 and System 7, were chosen as eligible systems to be installed. The Levelized Cost of Energy (LCOE result for System 2 was 0.2518 US$/kWh and for System 7 was 0.2265 US$/kWh by 2018 in the Base Scenario. Meanwhile, the Internal Rate of Return (IRR value fluctuated from 17.2% for System 2 to 31% for System 7.

  3. ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Nestle, Ursula; De Ruysscher, Dirk; Ricardi, Umberto; Geets, Xavier; Belderbos, Jose; Pöttgen, Christoph; Dziadiuszko, Rafal; Peeters, Stephanie; Lievens, Yolande; Hurkmans, Coen; Slotman, Ben; Ramella, Sara; Faivre-Finn, Corinne; McDonald, Fiona; Manapov, Farkhad; Putora, Paul Martin; LePéchoux, Cécile; Van Houtte, Paul

    2018-04-01

    Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

    2016-01-01

    Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry

    Directory of Open Access Journals (Sweden)

    David S. Lalush

    2013-05-01

    Full Text Available Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET. To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c. Lewis lung carcinoma (LLC mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.

  6. Targeting Cathepsin E in Pancreatic Cancer by a Small Molecule Allows In Vivo Detection

    Directory of Open Access Journals (Sweden)

    Edmund J. Keliher

    2013-07-01

    Full Text Available When resectable, invasive pancreatic ductal adenocarcinoma (PDAC is most commonly treated with surgery and radiochemotherapy. Given the intricate local anatomy and locoregional mode of dissemination, achieving clean surgical margins can be a significant challenge. On the basis of observations that cathepsin E (CTSE is overexpressed in PDAC and that an United States Food and Drug Administration (FDA-approved protease inhibitor has high affinity for CTSE, we have developed a CTSE optical imaging agent [ritonavir tetramethyl-BODIPY (RIT-TMB] for potential intraoperative use.We show nanomolar affinity [half maximal inhibitory concentration (IC50 of 39.9 ± 1.2 nM] against CTSE of the RIT-TMB in biochemical assays and intracellular accumulation and target-to-background ratios that allow specific delineation of individual cancer cells. This approach should be useful for more refined surgical staging, planning, and resection with curative intent.

  7. Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules.

    Science.gov (United States)

    Trenholme, Katharine; Marek, Linda; Duffy, Sandra; Pradel, Gabriele; Fisher, Gillian; Hansen, Finn K; Skinner-Adams, Tina S; Butterworth, Alice; Ngwa, Che Julius; Moecking, Jonas; Goodman, Christopher D; McFadden, Geoffrey I; Sumanadasa, Subathdrage D M; Fairlie, David P; Avery, Vicky M; Kurz, Thomas; Andrews, Katherine T

    2014-07-01

    Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Design of an Acoustic Target Intrusion Detection System Based on Small-Aperture Microphone Array

    Science.gov (United States)

    Zu, Xingshui; Guo, Feng; Huang, Jingchang; Zhao, Qin; Liu, Huawei; Li, Baoqing; Yuan, Xiaobing

    2017-01-01

    Automated surveillance of remote locations in a wireless sensor network is dominated by the detection algorithm because actual intrusions in such locations are a rare event. Therefore, a detection method with low power consumption is crucial for persistent surveillance to ensure longevity of the sensor networks. A simple and effective two-stage algorithm composed of energy detector (ED) and delay detector (DD) with all its operations in time-domain using small-aperture microphone array (SAMA) is proposed. The algorithm analyzes the quite different velocities between wind noise and sound waves to improve the detection capability of ED in the surveillance area. Experiments in four different fields with three types of vehicles show that the algorithm is robust to wind noise and the probability of detection and false alarm are 96.67% and 2.857%, respectively. PMID:28273838

  9. New targeted treatments for non-small-cell lung cancer – role of nivolumab

    Directory of Open Access Journals (Sweden)

    Zago G

    2016-08-01

    Full Text Available Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL, Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV, Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017 and non-squamous NSCLC (CheckMate 057. In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively. Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. Keywords: nivolumab, advanced non-small-cell lung cancer, immunotherapy, anti-PD-1

  10. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A. [Academic Medical Center, University of Amsterdam, Department of Radiation Oncology, Amsterdam (Netherlands); Schoot, Agustinus J.A.J. van de [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiation Oncology, Amsterdam (Netherlands); Buist, Marrije R. [Academic Medical Center, University of Amsterdam, Department of Gynaecology and Obstetrics, Amsterdam (Netherlands)

    2018-03-15

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V{sub 45Gy} for bowel bag was >275 cm{sup 3} and >200 cm{sup 3}, respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [German] In der vorliegenden Studie wurden die moeglichen klinischen Vorteile einer Zielvolumenpraezisierung durch Ausschluss des tumorfreien proximalen Gebaermutteranteils bei der ''image-guided adaptive radiotherapy

  11. Diurnal variations in proliferation and crypt survival suggest a small target cell population in mouse colon

    International Nuclear Information System (INIS)

    Dobbin, J.; Hamilton, E.

    1986-01-01

    Male C57BLasup(t) mice of two ages, 3-5 months (young) and 14-15 months (old) were given 11 or 15Gy whole body irradiation at different times through the day. The mice were killed after 4.5 days and the number of surviving crypts per circumference of jejunum, ileum, transverse colon and descending colon were scored. These results show crypt survival in the small and large intestine of 15-month-old mice. In the ileum the maximum crypt survival was found at 04.00 h and the minimum at 08.00 h. In the jejunum and both regions of the colon the maximum crypt survival occurred at 16.00 h. The nadir of crypt survival after 15 Gy was at 04.00 h in the jejunum and at 20.00 and 24.00 h in the transverse and descending colon, respectively. In young mice, crypt survival levels were similar to those found in old animals except at 04.00 h. when survival in the jejunum and ileum fell to 0.0004+-0.0002 and 0.0007+-0.0004, respectively. The lowest crypt survival in the colon of young mice also occurred at 04.00 h and in all four tissues the greatest number of crypts survived irradiation at 24.00 h. (author)

  12. The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders.

    Science.gov (United States)

    Guan, Jian; Harris, Paul; Brimble, Margaret; Lei, Yang; Lu, Jun; Yang, Yang; Gunn, Alistair J

    2015-06-01

    Exogenous IGF-1 protects the brain from ischemic injury and improves function. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake and mitogenic potential. In this review, the authors have discussed the efficacy, pharmacokinetics and mechanisms of IGF-1 derivatives on protecting acute brain injury, preventing memory impairment and improving recovery from neurological degenerative conditions evaluated in various animal models. We have included natural metabolites of IGF-1, glycine-proline-glutamate (GPE), cleaved from N-terminal IGF-1 and cyclic glycine-proline (cGP) as well as the structural analogues of GPE and cGP, glycine-2-methyl-proline-glutamate and cyclo-l-glycyl-l-2-allylproline, respectively. In addition, the regulatory role for cGP in bioavailability of IGF-1 has also been discussed. These small neuropeptides provide effective neuroprotection by offering an improved pharmacokinetic profile and more practical route of administration compared with IGF-1 administration. Developing modified neuropeptides to overcome the limitations of their endogenous counterparts represents a novel strategy of pharmaceutical discovery for neurological disorders. The mechanism of action may involve a regulation of IGF-1 bioavailability.

  13. Targeting overall equipment efficiency for small medium enterprises with irregular production system

    Science.gov (United States)

    Prasetyawan, Y.; Suef, M.; Claudia, L.; Handayani, F. D.

    2018-04-01

    Overall Equipment Effectiveness (OEE) is widely used to measure the maturity of a production system. The company will be considered as World Class Manufacturing if it reaches more than 85% value, with near perfect value for availability, performance and quality factor. This assessment is usually taken on industries with regular production times named shift system. A typical 8 hours shift system is used in OEE measurement and performance monitoring. There are few Small to Medium Enterprise (SME) perform regular production times with shift systems, others using irregular production systems. The irregular production time in the SME production system is used because of demand fluctuations. This paper shows a quantitative analysis as a part of manufacturing system design to achieve a specific value of OEE for SME with irregular production systems, for individual businesses as well as collective business systems (some companies use the same production facilities for several processes). The results of experiments on several companies are presented, as a basis for determining the technical strategy of achieving OEE values.

  14. New targeted treatments for non-small-cell lung cancer - role of nivolumab.

    Science.gov (United States)

    Zago, Giulia; Muller, Mirte; van den Heuvel, Michel; Baas, Paul

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors.

  15. In Search of Small Molecule Inhibitors Targeting the Flexible CK2 Subunit Interface

    Directory of Open Access Journals (Sweden)

    Benoît Bestgen

    2017-02-01

    Full Text Available Protein kinase CK2 is a tetrameric holoenzyme composed of two catalytic (α and/or α’ subunits and two regulatory (β subunits. Crystallographic data paired with fluorescence imaging techniques have suggested that the formation of the CK2 holoenzyme complex within cells is a dynamic process. Although the monomeric CK2α subunit is endowed with a constitutive catalytic activity, many of the plethora of CK2 substrates are exclusively phosphorylated by the CK2 holoenzyme. This means that the spatial and high affinity interaction between CK2α and CK2β subunits is critically important and that its disruption may provide a powerful and selective way to block the phosphorylation of substrates requiring the presence of CK2β. In search of compounds inhibiting this critical protein–protein interaction, we previously designed an active cyclic peptide (Pc derived from the CK2β carboxy-terminal domain that can efficiently antagonize the CK2 subunit interaction. To understand the functional significance of this interaction, we generated cell-permeable versions of Pc, exploring its molecular mechanisms of action and the perturbations of the signaling pathways that it induces in intact cells. The identification of small molecules inhibitors of this critical interaction may represent the first-choice approach to manipulate CK2 in an unconventional way.

  16. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective

    International Nuclear Information System (INIS)

    Raben, David; Helfrich, Barb; Bunn, Paul A.

    2004-01-01

    The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small-cell lung cancers (NSCLCs). This presents an opportune target for new treatment strategies designed to selectively interfere with the cancer cell growth cycle. Recent investigations into the biology of the EGFR and its downstream signaling pathways have reminded us of the complexity of cancer cell communications from the cytoplasm to the nucleus. Multiple pathways are activated with stimulation of the autocrine and paracrine EGFR loop, from the ras-raf-MEK activation of ERK 1/2 to the P13K-Akt pathway, each playing an important role in cancer cell survival, invasion, and angiogenesis. Preclinical studies have demonstrated that molecules targeting the EGFR, either through extracellular blockade or intracellular interference with the EGFR-associated tyrosine kinase, reversibly or irreversibly, inhibit cancer cell growth. Potent antitumor effects have been observed in human tumor xenograft models. Preclinical studies have also demonstrated cooperative effects when anti-EGFR agents are combined with radiation or chemotherapy. Many of these agents have now entered into advanced human clinical trials with modest dose-related toxicity despite chronic administration. Encouraging response rates with single-agent targeted therapy have been reported in heavily pretreated patients with advanced NSCLC. In addition, agents targeting the angiogenic pathway, which plays a key role in the regulation of angiogenesis, may play an important role in enhancing the efficacy of anti-EGFR agents. This article will focus on the biology, rationale, and preclinical studies with targeted anti-EGFR and antiangiogenic therapies for the management of NSCLC

  17. TU-H-CAMPUS-TeP1-03: Magnetically Focused Proton Irradiation of Small Volume Radiosurgery Targets

    Energy Technology Data Exchange (ETDEWEB)

    McAuley, GA; Slater, JM [Loma Linda University, Loma Linda, CA (United States); Wroe, AJ [Loma Linda University, Loma Linda, CA (United States); Loma Linda University Medical Center, Loma Linda, CA (United States)

    2016-06-15

    Purpose: To investigate the use of magnetic focusing for small volume proton radiosurgery targets using a triplet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies Methods: Fourteen quadrupole magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into k=3 Halbach cylinders with various field gradients (100 to 250 T/m) were designed and manufactured. Triplet combinations of the magnets were placed on a positioning track on our Gantry 1 treatment table. Unmodulated 127 MeV proton beams with initial diameters of 3 to 20 mm were delivered to a water tank using single-stage scattering. Depth and transverse dose distributions were measured using a PTW PR60020 diode detector and EBT3 film, respectively. This data was compared with unfocused passively collimated beams. Monte Carlo simulations were also performed - both for comparison with experimental data and to further investigate the potential of triplet magnetic focusing. Results: Experimental results using 150 T/m gradient magnets and 15 to 20 mm initial diameter beams show peak to entrance dose ratios that are ∼ 43 to 48 % larger compared with spot size matched 8 mm collimated beams (ie, transverse profile full-widths at 90% maximum dose match within 0.5 mm of focused beams). In addition, the focusing beams were ∼ 3 to 4.4 times more efficient per MU in dose to target delivery. Additional results using different magnet combinations will also be presented. Conclusion: Our results suggest that triplet magnetic focusing could reduce entrance dose and beam number while delivering dose to small (∼≤ 10 mm diameter) radiosurgery targets in less time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however other treatment sites can be also envisioned. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10-1).

  18. A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells.

    Science.gov (United States)

    Fu, Zhi-guang; Wang, Li; Cui, Hong-yong; Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

    2016-02-23

    CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression.

  19. Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

    International Nuclear Information System (INIS)

    Mejia, J.; Galvis-Alonso, O.Y.; Braga, J.; Correa, R.; Leite, J.P.; Simoes, M.V.

    2009-01-01

    Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multi pinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target's radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals. (author)

  20. Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Mejia, J.; Galvis-Alonso, O.Y. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Faculdade de Medicina. Dept. de Biologia Molecular], e-mail: mejia_famerp@yahoo.com.br; Braga, J. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Div. de Astrofisica; Correa, R. [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil). Div. de Ciencia Espacial e Atmosferica; Leite, J.P. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Neurologia, Psiquiatria e Psicologia Medica; Simoes, M.V. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Clinica Medica

    2009-08-15

    Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multi pinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target's radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals. (author)

  1. A nanobody targeting carcinoembryonic antigen as a promising molecular probe for non-small cell lung cancer.

    Science.gov (United States)

    Wang, Hao; Meng, Ai-Min; Li, Sheng-Hua; Zhou, Xiao-Liang

    2017-07-01

    Carcinoembryonic antigen (CEA) is a biomarker and therapy target for non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer. Nanobodies with high target specificity are promising candidates to function as anti‑CEA probes. In the present study, the targeting effects of an anti‑CEA nanobody obtained from phage display were investigated using technetium‑99 m (99mTc) and fluorescence labeling. In vitro binding and immunofluorescent staining assays, as well as in vivo blood clearance and biodistribution assays were performed. High specificity and affinity of the nanobody for CEA‑positive H460 cells was observed in vitro. The pharmacokinetics assay of the 99mTc‑nanobody in Wistar rats demonstrated that the nanobody had appropriate T1/2α and T1/2β, which were 20.2 and 143.5 min, respectively. The biodistribution assay using H460 xenograft‑bearing nude mice demonstrated a high ratio of signal in tumor compared with background, which confirmed that the nanobody may be useful as a molecular probe for CEA‑positive cancer, particularly in NSCLC.

  2. Small-molecule intramimics of formin autoinhibition: a new strategy to target the cytoskeletal remodeling machinery in cancer cells.

    Science.gov (United States)

    Lash, L Leanne; Wallar, Bradley J; Turner, Julie D; Vroegop, Steven M; Kilkuskie, Robert E; Kitchen-Goosen, Susan M; Xu, H Eric; Alberts, Arthur S

    2013-11-15

    Although the cancer cell cytoskeleton is a clinically validated target, few new strategies have emerged for selectively targeting cell division by modulating the cytoskeletal structure, particularly ways that could avoid the cardiotoxic and neurotoxic effects of current agents such as taxanes. We address this gap by describing a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics. In screening for DID-DAD disruptors that activate mDia, we identified two molecules called intramimics (IMM-01 and -02) that were sufficient to trigger actin assembly and microtubule stabilization, serum response factor-mediated gene expression, cell-cycle arrest, and apoptosis. In vivo analysis of IMM-01 and -02 established their ability to slow tumor growth in a mouse xenograft model of colon cancer. Taken together, our work establishes the use of intramimics and mDia-related formins as a new general strategy for therapeutic targeting of the cytoskeletal remodeling machinery of cancer cells. ©2013 AACR

  3. Future Freshwater Stress on Small Islands: Population, Aridity and Global Warming Targets

    Science.gov (United States)

    Karnauskas, K. B.; Schleussner, C. F.; Donnelly, J. P.; Anchukaitis, K. J.

    2017-12-01

    Small island developing states (SIDS) face multiple threats from anthropogenic climate change, including potential changes in freshwater resource availability. Future freshwater stress, including geographic and seasonal variability, has important implications for climate change adaptation scenarios for vulnerable human populations living on islands across the world ocean. Due to a mismatch in spatial scale between SIDS landforms and the horizontal resolution of global climate models (GCMs), SIDS are mostly unaccounted for in GCMs that are used to make future projections of global climate change and its regional impacts. Specific approaches are required to address this gap between broad-scale model projections and regional, policy-relevant outcomes. Here we apply a recently developed methodology to project future changes in aridity in combination with population projections associated with different shared socioeconomic pathways (SSPs) to evaluate overall changes in freshwater stress in SIDS at warming levels of 1.5°C and 2°C above pre-industrial levels. By accounting for evaporative demand a posteriori, we reveal a robust yet spatially variable tendency towards increasing aridity for 16 million people living on islands by mid-century. Although about half of the islands are projected to experience increased rainfall—predominantly in the deep tropics—projected changes in evaporation are more uniform, shifting the global distribution of changes in island freshwater balance towards greater aridity. In many cases, the magnitude of projected drying is comparable to the amplitude of the estimated observed interannual variability, with important consequences for extreme events. While we find that future population growth will dominate changes in projected freshwater stress especially towards the end of the century, projected changes in aridity are found to compound freshwater stress for the vast majority of SIDS. Particularly across the Caribbean region, a

  4. Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.

    Science.gov (United States)

    Sail, Vibhavari; Rizzo, Alessandro A; Chatterjee, Nimrat; Dash, Radha C; Ozen, Zuleyha; Walker, Graham C; Korzhnev, Dmitry M; Hadden, M Kyle

    2017-07-21

    Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate. The TLS DNA polymerase Rev1 serves as an integral scaffolding protein that mediates the assembly of the active multiprotein TLS complexes. Protein-protein interactions (PPIs) between the C-terminal domain of Rev1 (Rev1-CT) and the Rev1-interacting region (RIR) of other TLS DNA polymerases play an essential role in regulating TLS activity. To probe whether disrupting the Rev1-CT/RIR PPI is a valid approach for developing a new class of targeted anticancer agents, we designed a fluorescence polarization-based assay that was utilized in a pilot screen for small molecule inhibitors of this PPI. Two small molecule scaffolds that disrupt this interaction were identified, and secondary validation assays confirmed that compound 5 binds to Rev1-CT at the RIR interface. Finally, survival and mutagenesis assays in mouse embryonic fibroblasts and human fibrosarcoma HT1080 cells treated with cisplatin and ultraviolet light indicate that these compounds inhibit mutagenic Rev1/Polζ-dependent TLS in cells, validating the Rev1-CT/RIR PPI for future anticancer drug discovery and identifying the first small molecule inhibitors of TLS that target Rev1-CT.

  5. Target based screening of small molecule library identifies pregnelonene, a Nrf2 agonist, as a potential radioprotector in zebrafish

    International Nuclear Information System (INIS)

    Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Shrivastava, Nitisha; Indracanti, Prem Kumar; Ray, Jharna

    2014-01-01

    Reactive oxygen species, cellular oxidative stress, tissue inflammation and cell death are the downstream consequences of radiation exposures which ultimately could lead to organism death. Present study aims at identifying potential targets and screening of small molecule compound library for identifying novel and effective radioprotectors. In-silco analysis of known radioprotectors revealed three main function, antioxidant, anti-inflammation and antiapoptosis. In this study, a collection of small molecules (John Hopkins Clinical Compound Library, JHCCL) were screened for these different functions using the biological activity database of NCBI with the help of in-house developed python script. Further, filtering of the JHCCL was done by searching for molecules which are known to be active against target of radiobiological significance, Nrf-2. Close observation of potential hits identified, pregnenolone, as an Nrf-2 agonist which was further evaluated for radioprotection in zebrafish model. Pregnenolone rendered significant protection (at 40 μM; added 1 hour prior to 20 Gy gamma radiation) in terms of damage manifestations (pericardial edema, microcephaly, micropthalmia, yolk sac resorption, curvature of spine, blood flow, body length, heart-beat, blood clot, roughness of skin) and survival advantage (60%) when compared to irradiated control. Further, the ability of pregnenolone to act as a neuroprotectant was also carried out using in-house developed software for assessing neuromotor functions. In comparison to radiation alone group, pregnenolone was found to possess significant neuroactive functions and diminished radiation induced neuronal impairment. Over all these results suggests that pregnenolone is an effective radioprotector which warrants further investigation for validation of its radioprotective action in higher vertebrates. Apart from that the utility of approach to screen out bioactivity data base of various chemical compound libraries for possible

  6. SmallSat Missions Traveling to Planetary Targets from Near-Earth-Space: Applications for Space Physics

    Science.gov (United States)

    Espley, J. R.; Folta, D.

    2017-12-01

    Recent advances in propulsion technology and interplanetary navigation theoretically allow very small spacecraft to travel directly to planetary destinations from near-Earth-space. Because there are currently many launches with excess mass capability (NASA, military, and even commercial), we anticipate a dramatic increase in the number of opportunities for missions to planetary targets. Spacecraft as small as 12U CubeSats can use solar electric propulsion to travel from Earth-orbit to Mars-orbit in approximately 2-3 years. Space physics missions are particularly well suited for such mission architectures since state-of-the-art instrumentation to answer fundamental science questions can be accommodated in relatively small payload packages. For example, multi-point measurements of the martian magnetosphere, ionosphere, and crustal magnetic fields would yield important new science results regarding atmospheric escape and the geophysical history of the martian surface. These measurements could be accomplished by a pair of 12U CubeSats with world-class instruments that require only modest mass, power, and telemetry resources (e.g. Goddard's mini-fluxgate vector magnetometer).

  7. Characterizations of power loads on divertor targets for type-I, compound and small ELMs in the EAST superconducting tokamak

    DEFF Research Database (Denmark)

    Wang, L.; Xu, G.S.; Guo, H.Y.

    2013-01-01

    -III ELMy H-modes. The energy loss and divertor power load are systematically characterized for these different ELMy H-modes to provide a physics basis for the next-step high-power long-pulse operations in EAST. Both type-I and compound ELMs exhibit good confinement (H98(y,2) ∼ 1). A significant loss......The Experimental Advanced Superconducting Tokamak (EAST) has recently achieved a variety of H-mode regimes with different edge-localized mode (ELM) dynamics, including type-I ELMs, compound ELMs, which are manifested by the onset of a large spike followed by a sequence of small spikes on Dα......-III ELMs. It is remarkable that the new very small ELMy H-modes exhibit even lower target power deposition than type-III ELMs, with the peak heat flux generally below 1 MW m−2. These very small ELMs are usually accompanied by broadband fluctuations with frequencies ranging from 20 to 50 kHz, which may...

  8. On mechanism of low-energy heavy ions scattering on a target surface with small atomic mass

    Energy Technology Data Exchange (ETDEWEB)

    Umarov, F.F. E-mail: farid1945@yahoo.com; Bazarbaev, N.N.; Kudryashova, L.B.; Krylov, N.M

    2002-11-01

    In the present work, an experimental study of low-energy (E{sub 0}=20-500 eV) heavy Cs{sup +} ions scattering on target surfaces with small atomic masses (Al, Si, Ni) has been performed for more accurate definition of mechanism of scattering and evaluation of an opportunity for use of heavy ions scattering as a tool of surface layer analysis. It is shown that the dependence of the relative energies of scattered ions versus the initial energy E/E{sub 0} (E{sub 0}) for Si (E{sub b}=4.64 eV/atom) and Ni (E{sub b}=4.43 eV/atom) approximately coincide despite the fact that the mass of Ni atom is twice as large as that of the Si atom mass. At the same time their binding energies E{sub b} are approximately equal to each other. It is found that the scattering angles of Cs{sup +} ions considerably exceed a limiting scattering angle {theta}{sub lim} in a single collision. It has been established that the scattering of low-energy heavy ions by light targets is described by a non-binary mechanism of many-particle interactions (simultaneous ion interaction with several target atoms). It has been shown that during the many-particle interactions the structure of energy spectra disappears; high relative energy of scattering ions and their dependence on energy of bombardment is observed. It has been found that the energy of scattered ions depends on binding energy, melting temperature and packing density of target atoms.

  9. A false-alarm aware methodology to develop robust and efficient multi-scale infrared small target detection algorithm

    Science.gov (United States)

    Moradi, Saed; Moallem, Payman; Sabahi, Mohamad Farzan

    2018-03-01

    False alarm rate and detection rate are still two contradictory metrics for infrared small target detection in an infrared search and track system (IRST), despite the development of new detection algorithms. In certain circumstances, not detecting true targets is more tolerable than detecting false items as true targets. Hence, considering background clutter and detector noise as the sources of the false alarm in an IRST system, in this paper, a false alarm aware methodology is presented to reduce false alarm rate while the detection rate remains undegraded. To this end, advantages and disadvantages of each detection algorithm are investigated and the sources of the false alarms are determined. Two target detection algorithms having independent false alarm sources are chosen in a way that the disadvantages of the one algorithm can be compensated by the advantages of the other one. In this work, multi-scale average absolute gray difference (AAGD) and Laplacian of point spread function (LoPSF) are utilized as the cornerstones of the desired algorithm of the proposed methodology. After presenting a conceptual model for the desired algorithm, it is implemented through the most straightforward mechanism. The desired algorithm effectively suppresses background clutter and eliminates detector noise. Also, since the input images are processed through just four different scales, the desired algorithm has good capability for real-time implementation. Simulation results in term of signal to clutter ratio and background suppression factor on real and simulated images prove the effectiveness and the performance of the proposed methodology. Since the desired algorithm was developed based on independent false alarm sources, our proposed methodology is expandable to any pair of detection algorithms which have different false alarm sources.

  10. SU-E-T-533: Evaluation of Dose Calculation Accuracy for Small Elongated Targets On the Edge Linac

    International Nuclear Information System (INIS)

    Qin, Y; Wen, N; Snyder, K; Huang, Y; Zhao, B; Bellon, M; Li, H; Song, K; Kim, J; Gordon, J; Chetty, I

    2014-01-01

    Purpose: To evaluate output factors and dose calculation accuracy on a novel SRS linear accelerator, the Edge (Varian), for treatments of small, elongated targets using flattening filter free (FFF) beam. Methods: Total scatter/output factors (OF’s) for 24 elongated, small, high definition multi-leaf collimator (HDMLC)-defined fields were measured on the Edge machine using 6X FFF beam. 3 detectors were used in water tank: CC01 ion chamber (active volume 10cc), stereotactic photon diode (SFD) (active diameter 0.6mm, active thickness 0.06mm), Edge detector (active volume 0.0019cc). The 24 MLC apertures have widths ranging from 5 to 20mm and length/width ratio from 0.25 to 5. Readings were cross calibrated with CC04 at field size 3×3 cm. A beam model was developed using commissioning measurements for treatment planning in Eclipse (AAA, version 11). One representative patient case (IMRT, target volume 0.2cc, 4×4×14mm) was calculated using AAA 11 and delivered on the Edge. Results: Due to volume averaging effects, CC01 readings were 11.2±0.9% lower than SFD readings for 5mm field sizes. The Edge diode showed a uniform over-response of 2.6±0.7% compared to SFD. Calculation using AAA v11 showed the best agreement with SFD measurements (2.4±1.7% lower than SFD). The largest difference between AAA v11 and SFD occurs at 5mm field sizes. For the patient plan, dose delivered on Edge was measured to be 2.2% higher than AAA v11 calculation. Conclusion: Cross-calibrated SFD output measurements presented the best agreement with commissioned AAA v11 beam model. Field sizes smaller than 1cm posed challenges to both the detectors and the calculation algorithm. For the representative patient with small elongated target, AAA v11 and measurements agreed within ~2% on the Edge linac. Although encouraging, a more comprehensive study is required to validate the overall algorithmic accuracy

  11. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

    Science.gov (United States)

    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

  12. Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

    Directory of Open Access Journals (Sweden)

    J. Mejia

    2009-08-01

    Full Text Available Single-photon emission computed tomography (SPECT is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multipinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target’s radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals.

  13. Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

    DEFF Research Database (Denmark)

    Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

    2012-01-01

    Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

  14. On mechanism of low-energy heavy ions scattering on a target surface with small atomic mass

    CERN Document Server

    Umarov, F F; Kudryashova, L B; Krylov, N M

    2002-01-01

    In the present work, an experimental study of low-energy (E sub 0 =20-500 eV) heavy Cs sup + ions scattering on target surfaces with small atomic masses (Al, Si, Ni) has been performed for more accurate definition of mechanism of scattering and evaluation of an opportunity for use of heavy ions scattering as a tool of surface layer analysis. It is shown that the dependence of the relative energies of scattered ions versus the initial energy E/E sub 0 (E sub 0) for Si (E sub b =4.64 eV/atom) and Ni (E sub b =4.43 eV/atom) approximately coincide despite the fact that the mass of Ni atom is twice as large as that of the Si atom mass. At the same time their binding energies E sub b are approximately equal to each other. It is found that the scattering angles of Cs sup + ions considerably exceed a limiting scattering angle theta sub l sub i sub m in a single collision. It has been established that the scattering of low-energy heavy ions by light targets is described by a non-binary mechanism of many-particle inter...

  15. 99m Tc-HYNIC-(Ser)3 -J18 peptide: A radiotracer for non-small-cell lung cancer targeting.

    Science.gov (United States)

    Shaghaghi, Zahra; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2018-02-14

    Radiolabeled peptide could be a useful tool for the diagnosis of non-small-cell lung cancer (NSCLC). In this study, HYNIC-(Ser) 3 -J18 peptide was labeled with 99m Tc using EDDA/tricine as coligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular-specific binding and tumor targeting in A-549 cells and tumor-bearing mice, respectively. The high radiochemical purity was obtained and this radiolabeled peptide exhibited high stability in buffer and serum. The radiolabeled peptide showed high affinity for the A-549 cells with a dissociation constant value (K D ) of 4.4 ± 0.8 nm. The tumor-muscles ratios were 2.7 and 4.4 at 1 and 2 hr after injection of 99m Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 in tumor-bearing mice. The tumor uptake was decreased after preinjection with non-labeled peptide for this radiolabeled peptide in blocking experiment. The results of this study showed the 99m Tc-(EDDA/tricine)-(Ser) 3 -HYNIC-J18 peptide might be a promising radiolabeled peptide for NSCLC targeting. © 2018 John Wiley & Sons A/S.

  16. Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells

    International Nuclear Information System (INIS)

    Xue Yan; Bi Feng; Zhang Xueyong; Pan Yanglin; Liu Na; Zheng Yi; Fan Daiming

    2004-01-01

    Hypoxia-induced angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Rho family small GTPases are involved in this process, and Rac1, a prominent member of the Rho family, may be critical in regulating hypoxia-induced gene activation of several angiogenesis factors and tumor suppressors. To further define Rac1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock down gene expression of Rac1 in gastric cancer cell line AGS that expresses a high level of Rac1. Both the mRNA and protein levels of Rac1 in the AGS cells were decreased dramatically after transfection with a Rac1-specific siRNA vector. When the conditioned medium derived from the Rac1 downregulated AGS cells was applied to the human endothelial cells, it could significantly inhibit the cell proliferation. Further study proved that, VEGF and HIF-1α, two angiogenesis promoting factors, were found to be downregulated whereas p53 and VHL, which are tumor suppressors and angiogenesis inhibitors, were upregulated in the Rac1 siRNA transfected cells. Our results suggest that Rac1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting the Rac1 GTPase

  17. Identification of the functional binding pocket for compounds targeting small-conductance Ca²⁺-activated potassium channels.

    Science.gov (United States)

    Zhang, Miao; Pascal, John M; Schumann, Marcel; Armen, Roger S; Zhang, Ji-Fang

    2012-01-01

    Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class.

  18. Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

    Science.gov (United States)

    Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

    2012-01-01

    Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778

  19. Smart multifunctional nanoagents for in situ monitoring of small molecules with a switchable affinity towards biomedical targets

    Science.gov (United States)

    Shevchenko, Konstantin G.; Cherkasov, Vladimir R.; Nikitina, Irina L.; Babenyshev, Andrey V.; Nikitin, Maxim P.

    2018-02-01

    The great diversity of nanomaterials provides ample opportunities for constructing effective agents for biomedical applications ranging from biosensing to drug delivery. Multifunctional nanoagents that combine several features in a single particle are of special interest due to capabilities that substantially exceed those of molecular drugs. An ideal theranostic agent should simultaneously be an advanced biosensor to identify a disease and report the diagnosis and a biomedical actuator to treat the disease. While many approaches were developed to load a nanoparticle with various drugs for actuation of the diseased cells (e.g., to kill them), the nanoparticle-based approaches for the localized biosensing with real-time reporting of the marker concentration severely lag behind. Here, we show a smart in situ nanoparticle-based biosensor/actuator system that dynamically and reversibly changes its structural and optical properties in response to a small molecule marker to allow real-time monitoring of the marker concentration and adjustment of the system ability to bind its biomedical target. Using the synergistic combination of signal readout based on the localized surface plasmon resonance and an original method of fabrication of smart ON/OFF-switchable nanoagents, we demonstrate reversible responsiveness of the system to a model small molecule marker (antibiotic chloramphenicol) in a wide concentration range. The proposed approach can be used for the development of advanced multifunctional nanoagents for theranostic applications.

  20. Variations of target volume definition and daily target volume localization in stereotactic body radiotherapy for early-stage non–small cell lung cancer patients under abdominal compression

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chunhui, E-mail: chan@coh.org; Sampath, Sagus; Schultheisss, Timothy E.; Wong, Jeffrey Y.C.

    2017-07-01

    We aimed to compare gross tumor volumes (GTV) in 3-dimensional computed tomography (3DCT) simulation and daily cone beam CT (CBCT) with the internal target volume (ITV) in 4-dimensional CT (4DCT) simulation in stereotactic body radiotherapy (SBRT) treatment of patients with early-stage non–small cell lung cancer (NSCLC) under abdominal compression. We retrospectively selected 10 patients with NSCLC who received image-guided SBRT treatments under abdominal compression with daily CBCT imaging. GTVs were contoured as visible gross tumor on the planning 3DCT and daily CBCT, and ITVs were contoured using maximum intensity projection (MIP) images of the planning 4DCT. Daily CBCTs were registered with 3DCT and MIP images by matching of bony landmarks in the thoracic region to evaluate interfractional GTV position variations. Relative to MIP-based ITVs, the average 3DCT-based GTV volume was 66.3 ± 17.1% (range: 37.5% to 92.0%) (p < 0.01 in paired t-test), and the average CBCT-based GTV volume was 90.0 ± 6.7% (daily range: 75.7% to 107.1%) (p = 0.02). Based on bony anatomy matching, the center-of-mass coordinates for CBCT-based GTVs had maximum absolute shift of 2.4 mm (left-right), 7.0 mm (anterior-posterior [AP]), and 5.2 mm (superior-inferior [SI]) relative to the MIP-based ITV. CBCT-based GTVs had average overlapping ratio of 81.3 ± 11.2% (range: 45.1% to 98.9%) with the MIP-based ITV, and 57.7 ± 13.7% (range: 35.1% to 83.2%) with the 3DCT-based GTV. Even with abdominal compression, both 3DCT simulations and daily CBCT scans significantly underestimated the full range of tumor motion. In daily image-guided patient setup corrections, automatic bony anatomy-based image registration could lead to target misalignment. Soft tissue-based image registration should be performed for accurate treatment delivery.

  1. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

    Directory of Open Access Journals (Sweden)

    Ignat Drozdov

    Full Text Available Small intestinal (SI neuroendocrine tumors (NET are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene relevance network in SI-NETs. The network was confirmed to be non-random, scale-free, and highly modular. Functional analysis of gene co-expression modules revealed processes including 'Nervous system development', 'Immune response', and 'Cell-cycle'. Importantly, gene network topology and differential expression analysis identified over-expression of the GPCR signaling regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven CREB response element (CRE transcripts associated with proliferation and secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal preparations. All were up-regulated (p<0.035 with the exception of SCG3 which was not differently expressed. Forskolin (a direct cAMP activator, 10(-5 M significantly stimulated transcription of pCREB and 3/7 CREB targets, isoproterenol (a selective ß-adrenergic receptor agonist and cAMP activator, 10(-5 M stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2 and Serotonin [5-HT(2] receptor agonist, 10(-6 M stimulated 100% of targets as well as pCREB; CRE transcription correlated with the levels of cAMP accumulation and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8-fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin. Gene network inference and graph topology analysis in SI NETs suggests that SI NETs express neural GPCRs that activate different CRE targets associated with proliferation and secretion. In vitro studies, in a model NET cell system, confirmed that transcriptional

  2. Studying Teacher Moves

    Science.gov (United States)

    Goldstein, Michael

    2012-01-01

    In July 2011, Bill Gates told the "Wall Street Journal," "I'm enough of a scientist to want to say, "What is it about a great teacher?"" As a "practitioner" of sorts, the author has wondered the same thing for 15 years. The K-12 school sector generates little empirical research of any sort. And of this small amount, most is targeted to…

  3. An autonomous robot inspired by insect neurophysiology pursues moving features in natural environments

    Science.gov (United States)

    Bagheri, Zahra M.; Cazzolato, Benjamin S.; Grainger, Steven; O'Carroll, David C.; Wiederman, Steven D.

    2017-08-01

    Objective. Many computer vision and robotic applications require the implementation of robust and efficient target-tracking algorithms on a moving platform. However, deployment of a real-time system is challenging, even with the computational power of modern hardware. Lightweight and low-powered flying insects, such as dragonflies, track prey or conspecifics within cluttered natural environments, illustrating an efficient biological solution to the target-tracking problem. Approach. We used our recent recordings from ‘small target motion detector’ neurons in the dragonfly brain to inspire the development of a closed-loop target detection and tracking algorithm. This model exploits facilitation, a slow build-up of response to targets which move along long, continuous trajectories, as seen in our electrophysiological data. To test performance in real-world conditions, we implemented this model on a robotic platform that uses active pursuit strategies based on insect behaviour. Main results. Our robot performs robustly in closed-loop pursuit of targets, despite a range of challenging conditions used in our experiments; low contrast targets, heavily cluttered environments and the presence of distracters. We show that the facilitation stage boosts responses to targets moving along continuous trajectories, improving contrast sensitivity and detection of small moving targets against textured backgrounds. Moreover, the temporal properties of facilitation play a useful role in handling vibration of the robotic platform. We also show that the adoption of feed-forward models which predict the sensory consequences of self-movement can significantly improve target detection during saccadic movements. Significance. Our results provide insight into the neuronal mechanisms that underlie biological target detection and selection (from a moving platform), as well as highlight the effectiveness of our bio-inspired algorithm in an artificial visual system.

  4. Modelling small groundwater systems - the role of targeted field investigations and observational data in reducing model uncertainty

    Science.gov (United States)

    Abesser, Corinna; Hughes, Andrew; Boon, David

    2017-04-01

    Coastal dunes are delicate systems that are under threat from a variety of human and natural influences. Groundwater modelling can provide a better understanding of how these systems operate and can be a useful tool towards the effective management of a coastal dune system, e.g. through predicting impacts from climatic change, sea level rise and land use management. Because of their small size, typically 10 - 100 km2, models representing small dune aquifer systems are more sensitive to uncertainties in input data, model geometry and model parameterisation as well as to the availability of observational data. This study describes the development of a groundwater flow model for a small (8 km2) spit dune system, Braunton Burrows, on the Southwest coast of England, UK. The system has been extensively studied and its hydrology is thought to be well understood. However, model development revealed a high degree of uncertainty relating to model structure (definition of model boundary conditions) and parameterisation (e.g., transmissivity distributions within the model domain). An iterative approach was employed, integrating (1) sensitivity analyses, (2) targeted field investigations and (3) Monte Carlo simulations within a cycle of repeated interrogation of the model outputs, observed data and conceptual understanding. Assessment of "soft information" and targeted field investigations were an important part of this iterative modelling process. For example, a passive seismic survey (TROMINO®) provided valuable new data for the characterisation of concealed bedrock topography and thickness of superficial deposits. The data confirmed a generally inclined underlying wave cut rock shelf platform (as suggested by literature sources), revealed a buried valley, and led to a more detailed delineation of transmissivity zones within the model domain. Constructing models with increasingly more complex spatial distributions of transmissivity, resulted in considerable improvements in

  5. SU-F-T-211: Evaluation of a Dual Focusing Magnet System for the Treatment of Small Proton Targets

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, TT; McAuley, GA; Heczko, S; Slater, J [Loma Linda University, Loma Linda, CA (United States); Wroe, A [Loma Linda University, Loma Linda, CA (United States); Loma Linda University Medical Center, Loma Linda, CA (United States)

    2016-06-15

    Purpose: To investigate magnetic focusing for small volume proton targets using a doublet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies Methods: Monte Carlo computer simulations were performed using the Geant4 toolkit to compare dose depositions of proton beams transported through two focusing magnets or in their absence. Proton beams with energies of 127 MeV and initial diameters of 5, 8 and 10 mm were delivered through two identical focusing magnets similar to those currently in experimental use at Loma Linda University Medical Center. Analogous experiments used optimized configurations based on the simulation results. Dose was measured by a diode detector and Gafchromic EBT3 film and compared to simulation data. Based on results from the experimental data, an additional set of simulations was performed with an initial beam diameter of 18 mm and a two differing length magnets (40mm & 68mm). Results: Experimental data matched well with Monte Carlo simulations. However, under conditions necessary to produce circular beam spots at target depth, magnetically focused beams using two identical 40 mm length magnets did not meet all of our performance criteria of circular beam spots, improved peak to entrance (P/E) dose ratios and dose delivery efficiencies. The simulations using the longer 68 mm 2nd magnet yielded better results with 34% better P/E dose ratio and 20–50% better dose delivery efficiencies when compared to unfocused 10 mm beams. Conclusion: While magnetic focusing using two magnets with identical focusing power did not yield desired results, ongoing Monte Carlo simulations suggest that increasing the length of the 2nd magnet to 68 mm could improve P/E dose ratios and dose efficiencies. Future work includes additional experimental validation of the longer 2nd magnet setup as well as experiments with triplet magnet systems. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10-1).

  6. Image quality of grating target in model eye when viewed through a small-aperture corneal inlay.

    Science.gov (United States)

    Inoue, Makoto; Bissen-Miyajima, Hiroko; Arai, Hiroyuki; Noda, Toru; Ohnuma, Kazuhiko; Hirakata, Akito

    2014-07-01

    To evaluate the quality of the image of a grating target placed in a model eye and viewed through a small-aperture corneal inlay. Kyorin Eye Center, Tokyo, Japan. Experimental study. A Kamra corneal inlay was placed on the anterior surface of a fluid-filled model eye, and a United States Air Force target and a calibrated scale were placed on the inner surface of the model eye. With a flat contact lens or a contact or noncontact wide-angle viewing system, the contrast of the grating images and the field of view through the inlay were compared with those without the inlay. A blurred dark ring was observed with the flat contact lens and MiniQuad wide-viewing contact lens in the model eye with the inlay. The contrast of the gratings was significantly decreased at 16 cycles/mm (P=.028), 32 cycles/mm (P=.046), and 64 cycles/mm (P=.015). With the Resight noncontact wide-angle viewing system, the field of view was reduced from 62 degrees to 32 degrees when the front lens was at 7.0 mm and slightly reduced from 75 degrees to 62 degrees at 5.0 mm with the inlay. The contrast of grating images observed through the inlay was significantly reduced when viewed with the flat contact lens. The field of view through the wide-angle viewing system was also altered. However, the noncontact wide-angle viewing system may be recommended for vitreous surgeries in eyes with the inlay by adjusting the distance of the front lens from the cornea. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  7. Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer.

    Science.gov (United States)

    Voutila, Jon; Reebye, Vikash; Roberts, Thomas C; Protopapa, Pantelitsa; Andrikakou, Pinelopi; Blakey, David C; Habib, Robert; Huber, Hans; Saetrom, Pal; Rossi, John J; Habib, Nagy A

    2017-12-06

    Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Genomic Characterization of Non–Small-Cell Lung Cancer in African Americans by Targeted Massively Parallel Sequencing

    Science.gov (United States)

    Araujo, Luiz H.; Timmers, Cynthia; Bell, Erica Hlavin; Shilo, Konstantin; Lammers, Philip E.; Zhao, Weiqiang; Natarajan, Thanemozhi G.; Miller, Clinton J.; Zhang, Jianying; Yilmaz, Ayse S.; Liu, Tom; Coombes, Kevin; Amann, Joseph; Carbone, David P.

    2015-01-01

    Purpose Technologic advances have enabled the comprehensive analysis of genetic perturbations in non–small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date. Methods A custom panel was designed to cover the coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers. Clinical samples were sequenced on a massively parallel sequencing instrument, and anaplastic lymphoma kinase translocation was evaluated by fluorescent in situ hybridization. Results The study cohort included 99 patients (61% males, 94% smokers) comprising 31 squamous and 68 nonsquamous cell carcinomas. We detected 227 nonsilent variants in the coding sequence, including 24 samples with nonoverlapping, classic driver alterations. The frequency of driver mutations was not significantly different from that of whites, and no association was found between genetic ancestry and the presence of somatic mutations. Copy number alteration analysis disclosed distinguishable amplifications in the 3q chromosome arm in squamous cell carcinomas and pointed toward a handful of targetable alterations. We also found frequent SMARCA4 mutations and protein loss, mostly in driver-negative tumors. Conclusion Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions. PMID:25918285

  9. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  10. Production and dosimetric aspects of the potent Auger emitter 58mCo for targeted radionuclide therapy of small tumors

    International Nuclear Information System (INIS)

    Thisgaard, H.; Elema, D.R.; Jensen, M.

    2011-01-01

    Purpose: Based on theoretical calculations, the Auger emitter 58m Co has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state 58g Co is unfortunately unavoidable, as is ingrowth of the ground state following the isomeric decay of 58m Co. The impact of 58g Co as a β + - and γ-emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of 58m Co and 58g Co using a low-energy cyclotron. Also, the cellular S-values for 58m Co have been calculated and are presented here for the first time. Methods: 58m Co was produced via the 58 Fe(p,n) 58m Co nuclear reaction on highly enriched 58 Fe metal. In addition, radiochemical separations of produced radio-cobalt from nat Fe target material were performed. The theoretical subcellular dosimetry calculations for 58m Co and 58g Co were performed using the MIRD formalism, and the impact of the increasing ground state impurity on the tumor-to-normal-tissue dose ratios (TND) per disintegration as a function of time after end of bombardment (EOB) was calculated. Results: 192 ± 8 MBq of 58m Co was produced in the irradiation corresponding to a production yield of 10.7 MBq/μAh. The activity of 58g Co was measured to be 0.85% ± 0.04% of the produced 58m Co activity at EOB. The radio-cobalt yields in the rapid separations were measured to be >97% with no detectable iron contaminations in the cobalt fractions. Due to the unavoidable coproduction and ingrowth of the long-lived ground state 58g Co, the TND and the potency of the 58m Co decrease with time after EOB. If a future treatment with a 58m Co labeled compound is not initiated before, e.g., 21 h after EOB, the resulting TND will be approximately 50% of the TND of 'pure' 58m Co as a result of the increased normal tissue dose from

  11. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    OpenAIRE

    von Rechenberg Moritz; Peltier John M; Ahn Kwangmi; Zarembinski Thomas I; Askovich Peter S; An Steven S; Sahasrabudhe Sudhir; Fredberg Jeffrey J

    2011-01-01

    Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two qua...

  12. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain

    Science.gov (United States)

    Mistry, Pragnesh; Laird, Michelle H. W.; Schwarz, Ryan S.; Greene, Shannon; Dyson, Tristan; Snyder, Greg A.; Xiao, Tsan Sam; Chauhan, Jay; Fletcher, Steven; Toshchakov, Vladimir Y.; MacKerell, Alexander D.; Vogel, Stefanie N.

    2015-01-01

    Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein–protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors. PMID:25870276

  13. Manufacturing, testing and post-test examination of ITER divertor vertical target W small scale mock-ups

    International Nuclear Information System (INIS)

    Visca, Eliseo; Cacciotti, Emanuele; Komarov, Anton; Libera, Stefano; Litunovsky, Nikolay; Makhankov, Alexey; Mancini, Andrea; Merola, Mario; Pizzuto, Aldo; Riccardi, Bruno; Roccella, Selanna

    2011-01-01

    ENEA is involved in the International Thermonuclear Experimental Reactor (ITER) R and D activities. During the last years ENEA has set up and widely tested a manufacturing process, named Hot Radial Pressing (HRP), suitable for the construction of high heat flux plasma-facing components, such as the divertor targets. In the frame of the EFDA contract six mock-ups were manufactured by HRP in the ENEA labs using W monoblocks supplied by the Efremov Institute in St. Petersburg, Russian Federation and IG CuCrZr tubes. According to the technical specifications the mock-ups were examined by ultrasonic technique and after their acceptance they were delivered to the Efremov Institute TSEFEY-M e-beam facility for the thermal fatigue testing. The test consisted in 3000 cycles of 15 s heating and 15 s cooling at 10 MW/m 2 and finally 1000 cycles at 20 MW/m 2 . After the testing the ultrasonic non-destructive examination was repeated and the results compared with the investigation performed before the testing. A microstructure modification of the W monoblock material due to the overheating of the surfaces and the copper interlayer structure modification were observed in the high heat flux area. The leakage points of the mock-ups that did not conclude the testing were localized in the middle of the monoblock while they were expected between two monoblocks. This paper reports the manufacturing route, the thermal fatigue testing, the pre and post non destructive examination and finally the results of the destructive examination performed on the monoblock small scale mock-ups.

  14. Hitting the Moving Target of Program Choice.

    Science.gov (United States)

    Heinlein, Ken B.; Campbell, Edward M.; Fortune, Jon; Fortune, Barbara; Moore, Kay S.; Laird, Elva

    1998-01-01

    Comparison of what people with developmental disabilities in Wyoming and South Dakota wanted and received in programs in 1988 (N=2,927) and in 1996 (N=3,934) found that the percentage of people placed in their preferred setting rose substantially, from 51% to 84% in Wyoming and from 62% to 72% in South Dakota. (Author/DB)

  15. Moving Target Information Exploitation Electronic Learning

    Science.gov (United States)

    2005-10-01

    Traditional - ISR WebTAS – eLearning ................................................................. 6 MTIX e- Learning Technical Requirements...than on a specific schedule, so learners can take the curriculum when needed and at their own pace . E- Learning is a form of instructional authoring...can save training expenses, because it can be used over and over again. E- Learning also allows the user to study at his or her own convenience

  16. Radar Imaging of Stationary and Moving Targets

    Science.gov (United States)

    2012-06-28

    Sciences Research Institute. Member of Organizing Committee for introductory workshop at MSRI • June 14-18, 2010, arranged for AFRL (Matt Ferrara ) to...Schneible, Vincent Amuso, SciTech Publishing, Inc., 2010. 2. K. Voccola, B. Yazici, M. Ferrara , and M. Cheney, “On the relationship between the generalized...echo imaging using distributed apertures in multi-path,” IEEE Radar Conference, May, 2008, Rome, Italy . 14 10. “Wideband pulse-echo imaging using

  17. Moving Targets: Constructing Canons, 2013–2014

    OpenAIRE

    Hirsch, BD

    2015-01-01

    This review essay considers early modern dramatic authorship and canons in the context of two recent publications: an anthology of plays -- William Shakespeare and Others: Collaborative Plays (2013), edited by Jonathan Bate and Eric Rasmussen as a companion volume to the RSC Complete Works -- and a monograph study -- Jeremy Lopez's Constructing the Canon of Early Modern Drama (2014).

  18. Job Surfing: Move On to Move Up.

    Science.gov (United States)

    Martin, Justin

    1997-01-01

    Looks at the process of switching jobs and changing careers. Discusses when to consider options and make the move as well as the need to be flexible and open minded. Provides a test for determining the chances of promotion and when to move on. (JOW)

  19. Synthesis and in vitro experiments of carcinoma vascular endothelial targeting polymeric nano-micelles combining small particle size and supermagnetic sensitivity.

    Science.gov (United States)

    Zhang, Yi; Pan, Jielin; Xu, Qilan; Li, Hao; Wang, Jianhao; Zhang, Chao; Hong, Guobin

    2018-01-01

    Objective: To construct carcinoma vascular endothelial-targeted polymeric nanomicelles with high magnetic resonance imaging (MRI) sensitivity and to evaluate their biological safety and in vitro tumor-targeting effect, and to monitor their feasibility using clinical MRI scanner. Method: Amphiphilic block copolymer, poly(ethylene glycol)- b -poly(ε-caprolactone) (PEG-PCL) was synthesized via the ring-opening polymerization of ε-caprolactone (CL) initiated by poly(ethylene glycol) (PEG), in which cyclic pentapeptide Arg-Gly-Asp (cRGD) was conjugated with the terminal of hydrophilic PEG block. During the self-assembly of PEG-PCL micelles, superparamagnetic γ-Fe 2 O 3 nanoparticles (11 nm) was loaded into the hydrophobic core. The cRGD-terminated γ-Fe 2 O 3 -loaded polymeric micelles targeting to carcinoma vascular endothelial cells, were characterized in particle size, morphology, loading efficiency and so on, especially high MRI sensitivity in vitro. Normal hepatic vascular endothelial cells (ED25) were incubated with the resulting micelles for assessing their safety. Human hepatic carcinoma vascular endothelial cells (T3A) were cultured with the resulting micelles to assess the micelle uptake using Prussian blue staining and the cell signal intensity using MRI. Results: All the polymeric micelles exhibited ultra-small particle sizes with approximately 50 nm, high relaxation rate, and low toxicity even at high iron concentrations. More blue-stained iron particles were present in the targeting group than the non-targeting and competitive inhibition groups. In vitro MRI showed T 2 WI and T 2 relaxation times were significantly lower in the targeting group than in the other two groups. Conclusion: γ-Fe 2 O 3 -loaded PEG-PCL micelles not only possess ultra-small size and high superparamagnetic sensitivity, also can be actively targeted to carcinoma vascular endothelial cells by tumor-targeted cRGD. It appears to be a promising contrast agent for tumor-targeted

  20. Student-Centered Coaching: The Moves

    Science.gov (United States)

    Sweeney, Diane; Harris, Leanna S.

    2017-01-01

    Student-centered coaching is a highly-effective, evidence-based coaching model that shifts the focus from "fixing" teachers to collaborating with them to design instruction that targets student outcomes. But what does this look like in practice? "Student-Centered Coaching: The Moves" shows you the day-to-day coaching moves that…

  1. Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

    Science.gov (United States)

    Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

    2017-11-01

    It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  2. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Transfer RNA Derived Small RNAs Targeting Defense Responsive Genes Are Induced during Phytophthora capsici Infection in Black Pepper (Piper nigrum L.).

    Science.gov (United States)

    Asha, Srinivasan; Soniya, Eppurath V

    2016-01-01

    Small RNAs derived from transfer RNAs were recently assigned as potential gene regulatory candidates for various stress responses in eukaryotes. In this study, we report on the cloning and identification of tRNA derived small RNAs from black pepper plants in response to the infection of the quick wilt pathogen, Phytophthora capsici. 5'tRFs cloned from black pepper were validated as highly expressed during P. capsici infection. A high-throughput systematic analysis of the small RNAome (sRNAome) revealed the predominance of 5'tRFs in the infected leaf and root. The abundance of 5'tRFs in the sRNAome and the defense responsive genes as their potential targets indicated their regulatory role during stress response in black pepper. The 5'Ala(CGC) tRF mediated cleavage was experimentally mapped at the tRF binding sites on the mRNA targets of Non-expresser of pathogenesis related protein (NPR1), which was down-regulated during pathogen infection. Comparative sRNAome further demonstrated sequence conservation of 5'Ala tRFs across the angiosperm plant groups, and many important genes in the defense response were identified in silico as their potential targets. Our findings uncovered the diversity, differential expression and stress responsive functional role of tRNA-derived small RNAs during Phytophthora infection in black pepper.

  4. Threading the Needle: Small-Molecule Targeting of a Xenobiotic Receptor to Ablate Escherichia coli Polysaccharide Capsule Expression Without Altering Antibiotic Resistance.

    Science.gov (United States)

    Arshad, Mehreen; Goller, Carlos C; Pilla, Danielle; Schoenen, Frank J; Seed, Patrick C

    2016-04-15

    Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract and invasive infections worldwide, is rapidly acquiring multidrug resistance, hastening the need for selective new anti-infective agents. Here we demonstrate the molecular target of DU011, our previously discovered potent, nontoxic, small-molecule inhibitor of UPEC polysaccharide capsule biogenesis and virulence. Real-time polymerase chain reaction analysis and a target-overexpression drug-suppressor screen were used to localize the putative inhibitor target. A thermal shift assay quantified interactions between the target protein and the inhibitor, and a novel DNase protection assay measured chemical inhibition of protein-DNA interactions. Virulence of a regulatory target mutant was assessed in a murine sepsis model. MprA, a MarR family transcriptional repressor, was identified as the putative target of the DU011 inhibitor. Thermal shift measurements indicated the formation of a stable DU011-MprA complex, and DU011 abrogated MprA binding to its DNA promoter site. Knockout of mprA had effects similar to that of DU011 treatment of wild-type bacteria: a loss of encapsulation and complete attenuation in a murine sepsis model, without any negative change in antibiotic resistance. MprA regulates UPEC polysaccharide encapsulation, is essential for UPEC virulence, and can be targeted without inducing antibiotic resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Drugability of extracellular targets: discovery of small molecule drugs targeting allosteric, functional, and subunit-selective sites on GPCRs and ion channels.

    Science.gov (United States)

    Grigoriadis, Dimitri E; Hoare, Samuel R J; Lechner, Sandra M; Slee, Deborah H; Williams, John A

    2009-01-01

    Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and gamma-aminobutyric acid receptors, and the Ca(V)2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

  6. The incidence of inclusion of the sigmoid colon and small bowel in the planning target volume in radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Meerleer, G.O. de; Vakaet, L.; Neve, W.J. de; Villeirs, G.M.; Delrue, L.J.

    2004-01-01

    Background and purpose: in radiotherapy for prostate cancer, the rectum is considered the dose-limiting organ. The incidence of overlap between the sigmoid colon and/or small bowel and the planning target volume (PTV) as well as the dose to sigmoid colon and small bowel were investigated. Patients and methods: the CT data of 75 prostate cancer patients were analyzed. The clinical target volume (CTV) consisted of prostate and seminal vesicles. The PTV was defined as a three-dimensional expansion of the CTV with a 10-mm margin in craniocaudal and a 7-mm margin in the other directions. All patients were planned to a mean CTV dose of at least 76 Gy. Minimum CTV dose was set at 70 Gy. Dose inhomogeneity within the CTV was kept between 12% and 17%. Sigmoid colon was defined upward from the level where the rectum turned in a transverse plane. Contrast-filled small bowel was contoured on all slices where it was visible. The presence of sigmoid colon and/or small bowel in close vicinity to or overlapping with the PTV was recorded. For each case, the dose to the sigmoid colon and small bowel was calculated. Results: the PTV was found to overlap with the sigmoid colon in 60% and with the small bowel in 19% of the cases. In these patients, mean maximum dose to the sigmoid colon was 76.2 Gy (5th-95th percentile: 70.0-80.7 Gy). Mean maximum dose to the small bowel was 74.9 Gy (5th-95th percentile: 68.0-80.0 Gy). Conclusion: when systematically investigating the anatomic position of sigmoid colon and small bowel in patients accepted for prostate irradiation, parts of both organs were often observed in close vicinity to the PTV. Apart from the rectum, these organs may be dose-limiting in prostate radiotherapy. (orig.)

  7. The incidence of inclusion of the sigmoid colon and small bowel in the planning target volume in radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meerleer, G.O. de; Vakaet, L.; Neve, W.J. de [Dept. of Radiation Oncology, Gent Univ. Hospital, Gent (Belgium); Villeirs, G.M.; Delrue, L.J. [Dept. of Radiology, Gent Univ. Hospital, Gent (Belgium)

    2004-09-01

    Background and purpose: in radiotherapy for prostate cancer, the rectum is considered the dose-limiting organ. The incidence of overlap between the sigmoid colon and/or small bowel and the planning target volume (PTV) as well as the dose to sigmoid colon and small bowel were investigated. Patients and methods: the CT data of 75 prostate cancer patients were analyzed. The clinical target volume (CTV) consisted of prostate and seminal vesicles. The PTV was defined as a three-dimensional expansion of the CTV with a 10-mm margin in craniocaudal and a 7-mm margin in the other directions. All patients were planned to a mean CTV dose of at least 76 Gy. Minimum CTV dose was set at 70 Gy. Dose inhomogeneity within the CTV was kept between 12% and 17%. Sigmoid colon was defined upward from the level where the rectum turned in a transverse plane. Contrast-filled small bowel was contoured on all slices where it was visible. The presence of sigmoid colon and/or small bowel in close vicinity to or overlapping with the PTV was recorded. For each case, the dose to the sigmoid colon and small bowel was calculated. Results: the PTV was found to overlap with the sigmoid colon in 60% and with the small bowel in 19% of the cases. In these patients, mean maximum dose to the sigmoid colon was 76.2 Gy (5th-95th percentile: 70.0-80.7 Gy). Mean maximum dose to the small bowel was 74.9 Gy (5th-95th percentile: 68.0-80.0 Gy). Conclusion: when systematically investigating the anatomic position of sigmoid colon and small bowel in patients accepted for prostate irradiation, parts of both organs were often observed in close vicinity to the PTV. Apart from the rectum, these organs may be dose-limiting in prostate radiotherapy. (orig.)

  8. Quantification of activity by alpha-camera imaging and small-scale dosimetry within ovarian carcinoma micrometastases treated with targeted alpha therapy

    DEFF Research Database (Denmark)

    Chouin, N; Lindegren, S; Jensen, Holger

    2012-01-01

    Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified......% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity...... distribution received 100 µm might not be effectively treated by the examined regimen....

  9. Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

    International Nuclear Information System (INIS)

    Shirasaki, Takashi; Maruya, Shin-ichiro; Mizukami, Hiroki; Kakehata, Seiji; Kurotaki, Hidekachi; Yagihashi, Soroku; Shinkawa, Hideichi

    2008-01-01

    Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC). An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated in vitro. In addition, the in vivo effect of TS siRNA on tumor progression was assessed using a xenograft model. Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model. TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC

  10. Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Gergely Tóth

    Full Text Available The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson's and Alzheimer's diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228, that targets α-synuclein, a key protein in Parkinson's disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.

  11. Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study.

    LENUS (Irish Health Repository)

    Kissling, E

    2013-01-01

    Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case–control study in eight European Union (EU) Member States to estimate the 2011\\/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI \\/ acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011\\/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

  12. MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer

    OpenAIRE

    Minxia Liu; Kecheng Zhou; Yi Cao

    2016-01-01

    MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfectio...

  13. High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non-Small Cell Lung Cancer and Lung Metastases

    International Nuclear Information System (INIS)

    Fritz, Peter; Kraus, Hans-Joerg; Muehlnickel, Werner; Sassmann, Volker; Hering, Werner; Strauch, Konstantin

    2010-01-01

    Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of ≥20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.

  14. Moving and Being Moved: Implications for Practice.

    Science.gov (United States)

    Kretchmar, R. Scott

    2000-01-01

    Uses philosophical writings, a novel about baseball, and a nonfiction work on rowing to analyze levels of meaning in physical activity, showing why three popular methods for enhancing meaning have not succeeded and may have moved some students away from deeper levels of meaning. The paper suggests that using hints taken from the three books could…

  15. A Novel Class of Small Molecule Compounds that Inhibit Hepatitis C Virus Infection by Targeting the Prohibitin-CRaf Pathway

    Directory of Open Access Journals (Sweden)

    Shufeng Liu

    2015-11-01

    Full Text Available Identification of novel drug targets and affordable therapeutic agents remains a high priority in the fight against chronic hepatitis C virus (HCV infection. Here, we report that the cellular proteins prohibitin 1 (PHB1 and 2 (PHB2 are pan-genotypic HCV entry factors functioning at a post-binding step. While predominantly found in mitochondria, PHBs localize to the plasma membrane of hepatocytes through their transmembrane domains and interact with both EGFR and CRaf. Targeting PHB by rocaglamide (Roc-A, a natural product that binds PHB1 and 2, reduced cell surface PHB1 and 2, disrupted PHB-CRaf interaction, and inhibited HCV entry at low nanomolar concentrations. A structure-activity analysis of 32 synthetic Roc-A analogs indicated that the chiral, racemic version of aglaroxin C, a natural product biosynthetically related to Roc-A, displayed improved potency and therapeutic index against HCV infection. This study reveals a new class of HCV entry inhibitors that target the PHB1/2-CRaf pathway.

  16. A novel respiratory motion compensation strategy combining gated beam delivery and mean target position concept - A compromise between small safety margins and long duty cycles

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Kavanagh, Anthony; Webb, Steve; Brada, Michael

    2011-01-01

    Purpose: To evaluate a novel respiratory motion compensation strategy combining gated beam delivery with the mean target position (MTP) concept for pulmonary stereotactic body radiotherapy (SBRT). Materials and methods: Four motion compensation strategies were compared for 10 targets with motion amplitudes between 6 mm and 31 mm: the internal target volume concept (plan ITV ); the MTP concept where safety margins were adapted based on 4D dose accumulation (plan MTP ); gated beam delivery without margins for motion compensation (plan gated ); a novel approach combining gating and the MTP concept (plan gated and MTP ). Results: For 5/10 targets with an average motion amplitude of 9 mm, the differences in the mean lung dose (MLD) between plan gated and plan MTP were gated and MTP . Despite significantly shorter duty cycles, plan gated reduced the MLD by gated and MTP . The MLD was increased by 18% in plan MTP compared to that of plan gated and MTP . Conclusions: For pulmonary targets with motion amplitudes >10-15 mm, the combination of gating and the MTP concept allowed small safety margins with simultaneous long duty cycles.

  17. The CXCR4/SDF-1 chemokine receptor axis: a new target therapeutic for non-small cell lung cancer.

    Science.gov (United States)

    Otsuka, Shannon; Bebb, Gwyn

    2008-12-01

    Chemokines are proinflammatory chemoattractant cytokines that regulate cell trafficking and adhesion. The CXCR4 chemokine receptor and its ligand, stromal cell derived factor (SDF-1), constitute a chemokine/receptor axis that has attracted great interest because of an increasing understanding of its role in cancer, including lung cancer. The CXCR4/SDF-1 complex activates several pathways that mediate chemotaxis, migration and secretion of angiopoietic factors. Neutralization of SDF-1 by anti-SDF-1 or anti-CXCR4 monoclonal antibody in preclinical in vivo studies results in a significant decrease of non-small cell lung cancer metastases. Since anti-SDF-1/CXCR4 strategies have already been developed for use in combating human immunodeficiency virus infections, it is likely that these approaches will be used in clinical trials in non-small cell lung cancer in the very near future.

  18. Small interfering RNA targeting HIF-1{alpha} reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Staab, Adrian [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Paul Scherrer Institute (PSI), Villigen (Switzerland); Fleischer, Markus [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Wuerzburg Univ. (Germany). Medical Clinic II; Loeffler, Juergen; Einsele, Herrmann [Wuerzburg Univ. (Germany). Medical Clinic II; Said, Harun M.; Katzer, Astrid; Flentje, Michael [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Plathow, Christian [Freiburg Univ. (Germany). Dept. of Nuclear Medicine; Vordermark, Dirk [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Halle-Wittenberg Univ. (Germany). Dept. of Radiation Oncology

    2011-04-15

    Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1{alpha} expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1{alpha} siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1{alpha}. HIF-1{alpha} protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O{sub 2} (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1{alpha}-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER') was calculated as the ratio of the doses to achieve the same survival at 0.1% O{sub 2} as at ambient oxygen tensions. OER' was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1{alpha}-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1{alpha}-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. (orig.)

  19. Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

    International Nuclear Information System (INIS)

    Staab, Adrian; Fleischer, Markus; Wuerzburg Univ.; Loeffler, Juergen; Einsele, Herrmann; Said, Harun M.; Katzer, Astrid; Flentje, Michael; Plathow, Christian; Vordermark, Dirk; Halle-Wittenberg Univ.

    2011-01-01

    Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1α. HIF-1α protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O 2 (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1α-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER') was calculated as the ratio of the doses to achieve the same survival at 0.1% O 2 as at ambient oxygen tensions. OER' was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1α-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1α-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1α-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. (orig.)

  20. Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes

    Directory of Open Access Journals (Sweden)

    Dash Srikanta

    2006-11-01

    Full Text Available Abstract Background The antiviral action of interferon alpha targets the 5' untranslated region (UTR used by hepatitis C virus (HCV to translate protein by an internal ribosome entry site (IRES mechanism. Although this sequence is highly conserved among different clinical strains, approximately half of chronically infected hepatitis C patients do not respond to interferon therapy. Therefore, development of small interfering RNA (siRNA targeted to the 5'UTR to inhibit IRES mediated translation may represent an alternative approach that could circumvent the problem of interferon resistance. Results Four different plasmid constructs were prepared for intracellular delivery of siRNAs targeting the stem loop II-III of HCV 5' UTR. The effect of siRNA production on IRES mediated translation was investigated using chimeric clones between the gene for green fluorescence protein (GFP and IRES sequences of six different HCV genotypes. The siRNA targeted to stem loop II effectively mediated degradation of HCV IRES mRNA and inhibited GFP expression in the case of six different HCV genotypes, where as siRNAs targeted to stem loop III did not. Furthermore, intracytoplasmic expression of siRNA into transfected Huh-7 cells efficiently degraded HCV genomic RNA and inhibited core protein expression from infectious full-length infectious clones HCV 1a and HCV 1b strains. Conclusion These in vitro studies suggest that siRNA targeted to stem-loop II is highly effective inhibiting IRES mediated translation of the major genotypes of HCV. Stem-loop II siRNA may be a good target for developing an intracellular immunization strategy based antiviral therapy to inhibit hepatitis C virus strains that are not inhibited by interferon.

  1. Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

    Science.gov (United States)

    van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

    2018-05-03

    Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

    Directory of Open Access Journals (Sweden)

    Francesco Gentile

    2018-04-01

    Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

  3. Moving Field Guides

    Science.gov (United States)

    Cassie Meador; Mark Twery; Meagan. Leatherbury

    2011-01-01

    The Moving Field Guides (MFG) project is a creative take on site interpretation. Moving Field Guides provide an example of how scientific and artistic endeavors work in parallel. Both begin with keen observations that produce information that must be analyzed, understood, and interpreted. That interpretation then needs to be communicated to others to complete the...

  4. People on the Move

    Science.gov (United States)

    Mohan, Audrey

    2018-01-01

    The purpose of this 2-3 day lesson is to introduce students in Grades 2-4 to the idea that people move around the world for a variety of reasons. In this activity, students explore why people move through class discussion, a guided reading, and interviews. The teacher elicits student ideas using the compelling question (Dimension 1 of the C3…

  5. Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.

    Science.gov (United States)

    Wang, Hao; Mann, Paul A; Xiao, Li; Gill, Charles; Galgoci, Andrew M; Howe, John A; Villafania, Artjohn; Barbieri, Christopher M; Malinverni, Juliana C; Sher, Xinwei; Mayhood, Todd; McCurry, Megan D; Murgolo, Nicholas; Flattery, Amy; Mack, Matthias; Roemer, Terry

    2017-05-18

    Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. We provide genetic, biophysical, computational, biochemical, and pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is specifically required to develop broad-spectrum Gram-positive antibacterial agents targeting RF metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Embodied affectivity: On moving and being moved

    Directory of Open Access Journals (Sweden)

    Thomas eFuchs

    2014-06-01

    Full Text Available There is a growing body of research indicating that bodily sensation and behaviour strongly influences one’s emotional reaction towards certain situations or objects. On this background, a framework model of embodied affectivity is suggested: we regard emotions as resulting from the circular interaction between affective qualities or affordances in the environment and the subject’s bodily resonance, be it in the form of sensations, postures, expressive movements or movement tendencies. Motion and emotion are thus intrinsically connected: one is moved by movement (perception; impression; affection and moved to move (action; expression; e-motion. Through its resonance, the body functions as a medium of emotional perception: it colours or charges self-experience and the environment with affective valences while it remains itself in the background of one’s own awareness. This model is then applied to emotional social understanding or interaffectivity which is regarded as an intertwinement of two cycles of embodied affectivity, thus continuously modifying each partner’s affective affordances and bodily resonance. We conclude with considerations of how embodied affectivity is altered in psychopathology and can be addressed in psychotherapy of the embodied self.

  7. SU-F-T-645: To Test Spatial Anddosimetric Accuracy of Small Cranial Target Irradiation Based On 1.5 T MRIscans Using Static Arcs with MLCDefined Fields

    International Nuclear Information System (INIS)

    Brezovich, I; Wu, X; Popple, R; Shen, S; Cardan, R; Bolding, M; Fiveash, J; Kraus, J; Spencer, S

    2016-01-01

    Purpose: To test spatial and dosimetric accuracy of small cranial target irradiation based on 1.5 T MRI scans using static arcs with MLC-defined fields Methods: A plastic (PMMA) phantom simulating a small brain lesion was mounted on a GammaKnife headframe equipped with MRI localizer. The lesion was a 3 mm long, 3.175 mm diameter cylindrical cavity filled with MRI contrast. Radiochromic film passing through the cavity was marked with pin pricks at the cavity center. The cavity was contoured on an MRI image and fused with CT to simulate treatment of a lesion not visible on CT. The transfer of the target to CT involved registering the MRI contrast cannels of the localizer that were visible on both modalities. Treatments were planned to deliver 800 cGy to the cavity center using multiple static arcs with 5.0×2.4 mm MLC-defined fields. The phantom was aligned on a STx accelerator by registering the conebeam CT with the planning CT. Films from coronal and sagittal planes were scanned and evaluated using ImageJ software Results: Geographic errors in treatment based on 1.5 T scans agreed within 0.33, −0.27 and 1.21 mm in the vertical, lateral and longitudinal dimensions, respectively. The doses delivered to the cavity center were 7.2% higher than planned. The dose distributions were similar to those of a GammaKnife. Conclusion: Radiation can be delivered with an accelerator at mm accuracy to small cranial targets based on 1.5 MRI scans fused to CTs using a standard GammaKnife headframe and MRI localizer. MLC-defined static arcs produce isodose lines very similar to the GammaKnife.

  8. Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaopeng Ma

    2017-01-01

    Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

  9. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria

    2006-01-01

    the peptide loading rate. The effect was evident only for an allelic subset and strictly correlated with the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule. The residue forms the floor of the conserved pocket P1, located in the peptide binding site of MHC molecule. Apparently......, transient occupation of this pocket by the organic compound stabilizes the peptide-receptive conformation permitting rapid antigen loading. This interaction appeared restricted to the larger Gly(beta86) pocket and allowed striking enhancements of T cell responses for antigens presented by these "adamantyl......-susceptible" MHC molecules. As catalysts of antigen loading, compounds targeting P1 may be useful molecular tools to amplify the immune response. The observation, however, that the ligand repertoire can be affected through polymorphic sites form the outside may also imply that environmental factors could induce...

  10. Fibroblast growth factor receptor (FGFR) alterations in squamous differentiated bladder cancer: a putative therapeutic target for a small subgroup.

    Science.gov (United States)

    Baldia, Philipp H; Maurer, Angela; Heide, Timon; Rose, Michael; Stoehr, Robert; Hartmann, Arndt; Williams, Sarah V; Knowles, Margaret A; Knuechel, Ruth; Gaisa, Nadine T

    2016-11-01

    Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high. In the TCGA "squamous-like" subtype FGFR3 mutations were found in 4.9% and correlated with high FGFR3 RNA expression. Mutations of FGFR1 and FGFR2 were less frequent (2.4% and 1.2%). Hence, our comprehensive study provides novel insights into a subgroup of squamous differentiated bladder tumors that hold clues for novel therapeutic regimens and may benefit from FGFR3-targeted therapies.

  11. Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition

    International Nuclear Information System (INIS)

    Xing, Yu; Qi, Jin; Deng, Shixiong; Wang, Cheng; Zhang, Luyu; Chen, Junxia

    2013-01-01

    Integrin-linked kinase (ILK) is a multifunctional serine/threonine kinase. Accumulating evidences suggest that ILK are involved in cell–matrix interactions, cell proliferation, invasion, migration, angiogenesis and Epithelial–mesenchymal transition (EMT). However, the underlying mechanisms remain largely unknown. EMT has been postulated as a prerequisite for metastasis. The reports have demonstrated that EMT was implicated in metastasis of oral squamous cell carcinomas. Therefore, here we further postulate that ILK might participate in EMT of tongue cancer. We showed that ILK siRNA inhibited EMT with low N-cadherin, Vimentin, Snail, Slug and Twist as well as high E-cadherin expression in vivo and in vitro. We found that knockdown of ILK inhibited cell proliferation, migration and invasion as well as changed cell morphology. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3β as well as reduced expression of MMP2 and MMP9. Furthermore, we found that the tongue tumor with high metastasis capability showed higher ILK, Vimentin, Snail, Slug and Twist as well as lower E-cadherin expression in clinical specimens. Finally, ILK siRNA led to the suppression for tumorigenesis and metastasis in vivo. Our findings suggest that ILK could be a novel diagnostic and therapeutic target for tongue cancer. Highlights: • ILK siRNA influences cell morphology, cell cycle, migration and invasion. • ILK siRNA affects the expression of proteins associated with EMT. • ILK expression is related to EMT in clinical human tongue tumors. • ILK siRNA inhibits metastasis of the tongue cancer cells through suppressing EMT

  12. Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.

    Science.gov (United States)

    Bojadzic, Damir; Buchwald, Peter

    2018-05-30

    Protein-protein interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. SU-E-I-10: Investigation On Detectability of a Small Target for Different Slice Direction of a Volumetric Cone Beam CT Image

    International Nuclear Information System (INIS)

    Lee, C; Han, M; Baek, J

    2015-01-01

    Purpose: To investigate the detectability of a small target for different slice direction of a volumetric cone beam CT image and its impact on dose reduction. Methods: Analytic projection data of a sphere object (1 mm diameter, 0.2/cm attenuation coefficient) were generated and reconstructed by FDK algorithm. In this work, we compared the detectability of the small target from four different backprojection Methods: hanning weighted ramp filter with linear interpolation (RECON 1), hanning weighted ramp filter with Fourier interpolation (RECON2), ramp filter with linear interpolation (RECON 3), and ramp filter with Fourier interpolation (RECON4), respectively. For noise simulation, 200 photons per measurement were used, and the noise only data were reconstructed using FDK algorithm. For each reconstructed volume, axial and coronal slice were extracted and detection-SNR was calculated using channelized Hotelling observer (CHO) with dense difference-of-Gaussian (D-DOG) channels. Results: Detection-SNR of coronal images varies for different backprojection methods, while axial images have a similar detection-SNR. Detection-SNR 2 ratios of coronal and axial images in RECON1 and RECON2 are 1.33 and 1.15, implying that the coronal image has a better detectability than axial image. In other words, using coronal slices for the small target detection can reduce the patient dose about 33% and 15% compared to using axial slices in RECON 1 and RECON 2. Conclusion: In this work, we investigated slice direction dependent detectability of a volumetric cone beam CT image. RECON 1 and RECON 2 produced the highest detection-SNR, with better detectability in coronal slices. These results indicate that it is more beneficial to use coronal slice to improve detectability of a small target in a volumetric cone beam CT image. This research was supported by the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the IT Consilience Creative Program (NIPA-2014-H0201

  14. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  15. SU-E-I-10: Investigation On Detectability of a Small Target for Different Slice Direction of a Volumetric Cone Beam CT Image

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C; Han, M; Baek, J [Yonsei University, Incheon (Korea, Republic of)

    2015-06-15

    Purpose: To investigate the detectability of a small target for different slice direction of a volumetric cone beam CT image and its impact on dose reduction. Methods: Analytic projection data of a sphere object (1 mm diameter, 0.2/cm attenuation coefficient) were generated and reconstructed by FDK algorithm. In this work, we compared the detectability of the small target from four different backprojection Methods: hanning weighted ramp filter with linear interpolation (RECON 1), hanning weighted ramp filter with Fourier interpolation (RECON2), ramp filter with linear interpolation (RECON 3), and ramp filter with Fourier interpolation (RECON4), respectively. For noise simulation, 200 photons per measurement were used, and the noise only data were reconstructed using FDK algorithm. For each reconstructed volume, axial and coronal slice were extracted and detection-SNR was calculated using channelized Hotelling observer (CHO) with dense difference-of-Gaussian (D-DOG) channels. Results: Detection-SNR of coronal images varies for different backprojection methods, while axial images have a similar detection-SNR. Detection-SNR{sup 2} ratios of coronal and axial images in RECON1 and RECON2 are 1.33 and 1.15, implying that the coronal image has a better detectability than axial image. In other words, using coronal slices for the small target detection can reduce the patient dose about 33% and 15% compared to using axial slices in RECON 1 and RECON 2. Conclusion: In this work, we investigated slice direction dependent detectability of a volumetric cone beam CT image. RECON 1 and RECON 2 produced the highest detection-SNR, with better detectability in coronal slices. These results indicate that it is more beneficial to use coronal slice to improve detectability of a small target in a volumetric cone beam CT image. This research was supported by the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the IT Consilience Creative Program (NIPA-2014-H0201

  16. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    2010-04-01

    Full Text Available The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay.Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03

  17. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening.

    Science.gov (United States)

    An, Steven S; Askovich, Peter S; Zarembinski, Thomas I; Ahn, Kwangmi; Peltier, John M; von Rechenberg, Moritz; Sahasrabudhe, Sudhir; Fredberg, Jeffrey J

    2011-01-13

    A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  18. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    Directory of Open Access Journals (Sweden)

    von Rechenberg Moritz

    2011-01-01

    Full Text Available Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20 and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM. Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Results Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. Conclusions This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  19. An investigation of the challenges in reconstructing PET images of a freely moving animal

    International Nuclear Information System (INIS)

    Akhtar, Mahmood; Kyme, Andre; Meikle, Steven; Zhou, Victor; Fulton, Roger

    2013-01-01

    Imaging the brain of a freely moving small animal using positron emission tomography (PET) while simultaneously observing its behaviour is an important goal for neuroscience. While we have successfully demonstrated the use of line-of-response (LOR) rebinning to correct the head motion of confined animals, a large proportion of events may need to be discarded because they either 'miss' the detector array after transformation or fall out of the acceptance range of a sinogram. The proportion of events that would have been measured had motion not occurred, so-called 'lost events', is expected to be even larger for freely moving animals. Moreover, the data acquisition in the case of a freely moving animal is further complicated by a complex attenuation field. The aims of this study were (a) to characterise the severity of 'lost events' problem for the freely moving animal scenario, and (b) to investigate the relative impact of attenuation correction errors on quantitative accuracy of reconstructed images. A phantom study was performed to simulate the uncorrelated motion of a target and non-target source volume. A small animal PET scanner was used to acquire list-mode data for different sets of phantom positions. The list-mode data were processed using the standard LOR rebinning approach, and multiple frame variants of this designed to reduce discarded events. We found that LOR rebinning caused up to 86 % 'lost events', and artifacts that we attribute to incomplete projections, when applied to a freely moving target. This fraction was reduced by up to 18 % using the variant approaches, resulting in slightly reduced image artifacts. The effect of the non-target compartment on attenuation correction of the target volume was surprisingly small. However, for certain poses where the target and non-target volumes are aligned transaxially in the field-of-view, the attenuation problem becomes more complex and sophisticated correction methods will be required. We conclude that

  20. Synthesis, solubilization, and surface functionalization of highly fluorescent quantum dots for cellular targeting through a small molecule

    Science.gov (United States)

    Galloway, Justin F.

    To achieve long-term fluorescence imaging with quantum dots (QDs), a CdSe core/shell must first be synthesized. The synthesis of bright CdSe QDs is not trivial and as a consequence, the role of surfactant in nucleation and growth was investigated. It was found that the type of surfactant used, either phosphonic or fatty acid, played a pivotal role in the size of the CdSe core. The study of surfactant on CdSe synthesis, ultimately led to an electrical passivation method that utilized a short-chained phosphonic acid and highly reactive organometallic precursors to achieve high quantum yield (QY) as has been previously described. The synthesis of QDs using organometallic precursors and a phosphonic acid for passivation resulted in 4 out of 9 batches of QDs achieving QYs greater than 50% and 8 out of 9 batches with QYs greater than 35%. The synthesis of CdSe QDs was done in organic solutions rendering the surface of the particle hydrophobic. To perform cell-targeting experiments, QDs must be transferred to water. The transfer of QDs to water was successfully accomplished by using single acyl chain lipids. A systematic study of different lipid combinations and coatings demonstrated that 20-40 mol% single acyl chained lipids were able to transfer QDs to water resulting in monodispersed, stable QDs without adversely affecting the QY. The advantage to water solubilization using single acyl chain lipids is that the QD have a hydrodynamic radius less than 15 nm, QYs that can exceed 50% and additional surface functionalization can be down using the reactive sites incorporated into the lipid bilayer. QDs that are bright and stable in water were studied for the purpose of targeting G protein-coupled Receptors (GPCR). GPCRs are transmembrane receptors that internalize extracellular cues, and thus mediate signal transduction. The cyclic Adenosine Monophosphate Receptor 1 of the model organism Dictyostelium disodium was the receptor of interest. The Halo protein, a genetically

  1. Synergistic Protective Effects of Mitochondrial Division Inhibitor 1 and Mitochondria-Targeted Small Peptide SS31 in Alzheimer's Disease.

    Science.gov (United States)

    Reddy, P Hemachandra; Manczak, Maria; Yin, XiangLing; Reddy, Arubala P

    2018-01-01

    The purpose of our study was to determine the synergistic protective effects of mitochondria-targeted antioxidant SS31 and mitochondria division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Using biochemical methods, we assessed mitochondrial function by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity, mitochondrial ATP, and GTPase Drp1 enzymatic activity in mutant AβPP cells. Using biochemical methods, we also measured cell survival and apoptotic cell death. Amyloid-β (Aβ) levels were measured using sandwich ELISA, and using real-time quantitative RT-PCR, we assessed mtDNA (mtDNA) copy number in relation to nuclear DNA (nDNA) in all groups of cells. We found significantly reduced levels of Aβ40 and Aβ42 in mutant AβPP cells treated with SS31, Mdivi1, and SS31+Mdivi1, and the reduction of Aβ42 levels were much higher in SS31+Mdivi1 treated cells than individual treatments of SS31 and Mdivi1. The levels of mtDNA copy number and cell survival were significantly increased in SS31, Mdivi1, and SS31+Mdivi1 treated mutant AβPP cells; however, the increased levels of mtDNA copy number and cell survival were much higher in SS31+Mdivi1 treated cells than individual treatments of SS31 and Mdivi1. Mitochondrial dysfunction is significantly reduced in SS31, Mdivi1, and SS31+Mdivi1 treated mutant AβPP cells; however, the reduction is much higher in cells treated with both SS31+Mdvi1. Similarly, GTPase Drp1 activity is reduced in all treatments, but reduced much higher in SS31+Mdivi1 treated cells. These observations strongly suggest that combined treatment of SS31+Mdivi1 is effective than individual treatments of SS31 and Mdivi1. Therefore, we propose that combined treatment of SS31+Mdivi1 is a better therapeutic strategy for AD. Ours is the first study to investigate combined treatment of mitochondria-targeted antioxidant SS31 and mitochondrial division inhibitor 1 in AD neurons.

  2. Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

    Directory of Open Access Journals (Sweden)

    Charu Sharma

    2015-01-01

    Full Text Available The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2 which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.

  3. Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson's disease.

    Science.gov (United States)

    Mercado, Gabriela; Castillo, Valentina; Soto, Paulina; López, Nélida; Axten, Jeffrey M; Sardi, Sergio P; Hoozemans, Jeroen J M; Hetz, Claudio

    2018-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to the progressive decline of motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence suggest that altered proteostasis is a salient feature of PD, highlighting perturbations to the endoplasmic reticulum (ER), the main compartment involved in protein folding and secretion. PERK is a central ER stress sensor that enforces adaptive programs to recover homeostasis through a block of protein translation and the induction of the transcription factor ATF4. In addition, chronic PERK signaling results in apoptosis induction and neuronal dysfunction due to the repression in the translation of synaptic proteins. Here we confirmed the activation of PERK signaling in postmortem brain tissue derived from PD patients and three different rodent models of the disease. Pharmacological targeting of PERK by the oral administration of GSK2606414 demonstrated efficient inhibition of the pathway in the SNpc after experimental ER stress stimulation. GSK2606414 protected nigral-dopaminergic neurons against a PD-inducing neurotoxin, improving motor performance. The neuroprotective effects of PERK inhibition were accompanied by an increase in dopamine levels and the expression of synaptic proteins. However, GSK2606414 treated animals developed secondary effects possibly related to pancreatic toxicity. This study suggests that strategies to attenuate ER stress levels may be effective to reduce neurodegeneration in PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Target volume for postoperative radiotherapy in non-small cell lung cancer: Results from a prospective trial

    International Nuclear Information System (INIS)

    Kępka, Lucyna; Bujko, Krzysztof; Bujko, Magdalena; Matecka-Nowak, Mirosława; Salata, Andrzej; Janowski, Henryk; Rogowska, Danuta; Cieślak-Żerańska, Ewa; Komosińska, Katarzyna; Zawadzka, Anna

    2013-01-01

    Background and purpose: A previous prospective trial reported that three-dimensional conformal postoperative radiotherapy (PORT) for pN2 NSCLC patients using a limited clinical target volume (CTV) had a late morbidity rate and pulmonary function that did not differ from those observed in pN1 patients treated with surgery without PORT. The aim of this study was to assess locoregional control and localization of failure in patients treated with PORT. Materials and methods: The pattern of locoregional failure was evaluated retrospectively in 151 of 171 patients included in the PORT arm. The CTV included the involved lymph node stations and those with a risk of invasion >10%. Competing risk analysis was used to assess the incidence of locoregional failure and its location outside the CTV. Results: Overall survival at 5 years was 27.1% with a median follow-up of 67 months for 40 living patients. The 5-year cumulative incidence of locoregional failure was 19.4% (95% CI: 18.2–20.5%) including a failure rate of 2% (95% CI: 0–17%) in locations outside or at the border of the CTV. Conclusions: The use of limited CTV was associated with acceptable risk of geographic miss. Overall locoregional control was similar to that reported by other studies using PORT for pN2 patients

  5. Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.

    Science.gov (United States)

    Chamilos, Georgios; Lionakis, Michail S; Kontoyiannis, Dimitrios P

    2018-01-06

    Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  6. Inhibition of Hepatitis C Virus in Mice by a Small Interfering RNA Targeting a Highly Conserved Sequence in Viral IRES Pseudoknot.

    Directory of Open Access Journals (Sweden)

    Jae-Su Moon

    Full Text Available The hepatitis C virus (HCV internal ribosome entry site (IRES that directs cap-independent viral translation is a primary target for small interfering RNA (siRNA-based HCV antiviral therapy. However, identification of potent siRNAs against HCV IRES by bioinformatics-based siRNA design is a challenging task given the complexity of HCV IRES secondary and tertiary structures and association with multiple proteins, which can also dynamically change the structure of this cis-acting RNA element. In this work, we utilized siRNA tiling approach whereby siRNAs were tiled with overlapping sequences that were shifted by one or two nucleotides over the HCV IRES stem-loop structures III and IV spanning nucleotides (nts 277-343. Based on their antiviral activity, we mapped a druggable region (nts 313-343 where the targets of potent siRNAs were enriched. siIE22, which showed the greatest anti-HCV potency, targeted a highly conserved sequence across diverse HCV genotypes, locating within the IRES subdomain IIIf involved in pseudoknot formation. Stepwise target shifting toward the 5' or 3' direction by 1 or 2 nucleotides reduced the antiviral potency of siIE22, demonstrating the importance of siRNA accessibility to this highly structured and sequence-conserved region of HCV IRES for RNA interference. Nanoparticle-mediated systemic delivery of the stability-improved siIE22 derivative gs_PS1 siIE22, which contains a single phosphorothioate linkage on the guide strand, reduced the serum HCV genome titer by more than 4 log10 in a xenograft mouse model for HCV replication without generation of resistant variants. Our results provide a strategy for identifying potent siRNA species against a highly structured RNA target and offer a potential pan-HCV genotypic siRNA therapy that might be beneficial for patients resistant to current treatment regimens.

  7. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-09

    Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation\\/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.

  8. A novel small molecule inhibitor of influenza A viruses that targets polymerase function and indirectly induces interferon.

    Directory of Open Access Journals (Sweden)

    Mila Brum Ortigoza

    Full Text Available Influenza viruses continue to pose a major public health threat worldwide and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The antiviral cytokine, interferon (IFN is an essential mediator of the innate immune response and influenza viruses, like many viruses, have evolved strategies to evade this response, resulting in increased replication and enhanced pathogenicity. A cell-based assay that monitors IFN production was developed and applied in a high-throughput compound screen to identify molecules that restore the IFN response to influenza virus infected cells. We report the identification of compound ASN2, which induces IFN only in the presence of influenza virus infection. ASN2 preferentially inhibits the growth of influenza A viruses, including the 1918 H1N1, 1968 H3N2 and 2009 H1N1 pandemic strains and avian H5N1 virus. In vivo, ASN2 partially protects mice challenged with a lethal dose of influenza A virus. Surprisingly, we found that the antiviral activity of ASN2 is not dependent on IFN production and signaling. Rather, its IFN-inducing property appears to be an indirect effect resulting from ASN2-mediated inhibition of viral polymerase function, and subsequent loss of the expression of the viral IFN antagonist, NS1. Moreover, we identified a single amino acid mutation at position 499 of the influenza virus PB1 protein that confers resistance to ASN2, suggesting that PB1 is the direct target. This two-pronged antiviral mechanism, consisting of direct inhibition of virus replication and simultaneous activation of the host innate immune response, is a unique property not previously described for any single antiviral molecule.

  9. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    Science.gov (United States)

    Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.

    2015-09-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

  10. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    International Nuclear Information System (INIS)

    Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Valvo, F; Fossati, P; Ciocca, M; Ferrari, A

    2015-01-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5–30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo ® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus ® chamber. An EBT3 ® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification. (paper)

  11. PARALLEL MOVING MECHANICAL SYSTEMS

    Directory of Open Access Journals (Sweden)

    Florian Ion Tiberius Petrescu

    2014-09-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Moving mechanical systems parallel structures are solid, fast, and accurate. Between parallel systems it is to be noticed Stewart platforms, as the oldest systems, fast, solid and precise. The work outlines a few main elements of Stewart platforms. Begin with the geometry platform, kinematic elements of it, and presented then and a few items of dynamics. Dynamic primary element on it means the determination mechanism kinetic energy of the entire Stewart platforms. It is then in a record tail cinematic mobile by a method dot matrix of rotation. If a structural mottoelement consists of two moving elements which translates relative, drive train and especially dynamic it is more convenient to represent the mottoelement as a single moving components. We have thus seven moving parts (the six motoelements or feet to which is added mobile platform 7 and one fixed.

  12. Modeling of human prokineticin receptors: interactions with novel small-molecule binders and potential off-target drugs.

    Directory of Open Access Journals (Sweden)

    Anat Levit

    Full Text Available The Prokineticin receptor (PKR 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs, their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. PKs and their receptors play important roles under various physiological conditions such as maintaining circadian rhythm and pain perception, as well as regulating angiogenesis and modulating immunity. Identifying binding sites for known antagonists and for additional potential binders will facilitate studying and regulating these novel receptors. Blocking PKRs may serve as a therapeutic tool for various diseases, including acute pain, inflammation and cancer.Ligand-based pharmacophore models were derived from known antagonists, and virtual screening performed on the DrugBank dataset identified potential human PKR (hPKR ligands with novel scaffolds. Interestingly, these included several HIV protease inhibitors for which endothelial cell dysfunction is a documented side effect. Our results suggest that the side effects might be due to inhibition of the PKR signaling pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement with the well-established canonical TM-bundle binding site of family A GPCRs. Furthermore, the docking results highlight residues that may form specific contacts with the ligands. These contacts provide structural explanation for the importance of several chemical features that were obtained from the structure-activity analysis of known binders. With the exception of a single loop residue that might be perused in the future for obtaining subtype-specific regulation, the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In addition, analysis of the intracellular regions highlights variable regions that may provide subtype specificity.

  13. The Moving image

    DEFF Research Database (Denmark)

    Hansen, Lennard Højbjerg

    2014-01-01

    Every day we are presented with bodily expressions in audiovisual media – by anchors, journalists and characters in films for instance. This article explores how body language in the moving image has been and can be approached in a scholarly manner.......Every day we are presented with bodily expressions in audiovisual media – by anchors, journalists and characters in films for instance. This article explores how body language in the moving image has been and can be approached in a scholarly manner....

  14. miR-32 inhibits proliferation, epithelial–mesenchymal transition, and metastasis by targeting TWIST1 in non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Li L

    2016-03-01

    Full Text Available Lei Li,1,* Dapeng Wu2,* 1Department of Pneumology, 2Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, Henan, People’s Republic of China *These authors contributed equally to this work Background: By analyzing published microRNA microarray studies, miR-32 was found to be markedly reduced in non-small-cell lung cancer (NSCLC tissues compared with that in nontumor tissues. However, little is known about its role and molecular mechanism involved in NSCLC development and progression. Here, we report the effect of miR-32 on NSCLC cell proliferation, epithelial–mesenchymal transition (EMT, and metastasis. Methods: Quantitative real-time PCR was performed to detect the expression level of miR-32 in primary NSCLC cases and cell lines. miR-32-overexpressing H1299 and A549 cells were constructed by lipofection transfection. MTT, transwell chamber, and Western blot assays were used to assess the effect of miR-32 on proliferation, EMT, and metastasis of NSCLC cells, respectively. Target prediction and luciferase reporter assays were performed to investigate the targets of miR-32. Tumor formation assay in vivo was performed to investigate the antitumor effect of miR-32. Results: An inverse correlation existed between miR-32 expression level and NSCLC cell proliferation, EMT, and metastasis, and upregulation of miR-32 repressed NSCLC cell proliferation, EMT, and metastasis. Moreover, we identified and validated that TWIST1 was a direct target of miR-32, and miR-32 regulated NSCLC cell proliferation, EMT, and metastasis, at least in part via modulation of TWIST1. The animal experiments showed that overexpression of miR-32 inhibited the growth of NSCLC tumors in vivo. Keywords: non-small-cell lung cancer, miR-32, TWIST1, proliferation, EMT, nude mice

  15. Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Li, Weina; He, Fei

    2014-01-01

    Highlights: • Expression of MMD is increased in lung cancer tissues. • Knockdown of MMD inhibits growth of A549 and LLC cells in vitro and in vivo. • MMD is a direct functional target of miR-140-5p. • MiR-140-5p/MMD axis regulates Erk1/2 signaling. - Abstract: Monocyte to macrophage differentiation-associated (MMD) is identified in macrophages as a gene associated with the differentiation from monocytes to macrophages. Recent microarray analysis for non-small cell lung cancer (NSCLC) suggests that MMD is an important signature associated with relapse and survival among patients with NSCLC. Therefore, we speculate that MMD likely plays a role in lung cancer. In this study, we found that the protein level of MMD was increased in lung cancer compared to benign lung tissues, and knockdown of MMD inhibited the growth of A549 and Lewis lung cancer cells (LLC) in vitro and in vivo. Integrated analysis demonstrated that MMD was a direct functional target of miR-140-5p. Furthermore, we found that miR-140-5p/MMD axis could affect the cell proliferation of lung cancer cells by regulating Erk signaling. Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer

  16. The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

    Science.gov (United States)

    Lai, Yi-Hua; Yu, Sung-Liang; Chen, Hsuan-Yu; Wang, Chi-Chung; Chen, Huei-Wen; Chen, Jeremy J W

    2013-05-01

    HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

  17. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    International Nuclear Information System (INIS)

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

  18. Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of cisplatin-resistant non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Fuquan; Shen, Mingjing; Yang, Li; Yang, Xiaodong; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2017-08-03

    Development of cisplatin-resistance is an obstacle in non-small cell lung cancer (NSCLC) therapeutics. To investigate which molecules are associated with cisplatin-resistance, we analyzed expression profiles of several DNA repair and anti-apoptosis associated molecules in parental (A549P and H157P) and cisplatin-resistant (A549CisR and H157CisR) NSCLC cells. We detected constitutively upregulated nuclear ATM and cytosolic Mcl-1 molcules in cisplatin-resistant cells compared with parental cells. Increased levels of phosphorylated ATM (p-ATM) and its downstream molecules, CHK2, p-CHK2, p-53, and p-p53 were also detected in cisplatin-resistant cells, suggesting an activation of ATM signaling in these cells. Upon inhibition of ATM and Mcl-1 expression/activity using specific inhibitors of ATM and/or Mcl-1, we found significantly enhanced cisplatin-cytotoxicity and increased apoptosis of A549CisR cells after cisplatin treatment. Several A549CisR-derived cell lines, including ATM knocked down (A549CisR-siATM), Mcl-1 knocked down (A549CisR-shMcl1), ATM/Mcl-1 double knocked down (A549CisR-siATM/shMcl1) as well as scramble control (A549CisR-sc), were then developed. Higher cisplatin-cytotoxicity and increased apoptosis were observed in A549CisR-siATM, A549CisR-shMcl1, and A549CisR-siATM/shMcl1 cells compared with A549CisR-sc cells, and the most significant effect was shown in A549CisR-siATM/shMcl1 cells. In in vivo mice studies using subcutaneous xenograft mouse models developed with A549CisR-sc and A549CisR-siATM/shMcl1 cells, significant tumor regression in A549CisR-siATM/shMcl1 cells-derived xenografts was observed after cisplatin injection, but not in A549CisR-sc cells-derived xenografts. Finally, inhibitor studies revealed activation of Erk signaling pathway was most important in upregulation of ATM and Mcl-1 molcules in cisplatin-resistant cells. These studies suggest that simultaneous blocking of ATM/Mcl-1 molcules or downstream Erk signaling may recover the

  19. Target size matters: target errors contribute to the generalization of implicit visuomotor learning.

    Science.gov (United States)

    Reichenthal, Maayan; Avraham, Guy; Karniel, Amir; Shmuelof, Lior

    2016-08-01

    The process of sensorimotor adaptation is considered to be driven by errors. While sensory prediction errors, defined as the difference between the planned and the actual movement of the cursor, drive implicit learning processes, target errors (e.g., the distance of the cursor from the target) are thought to drive explicit learning mechanisms. This distinction was mainly studied in the context of arm reaching tasks where the position and the size of the target were constant. We hypothesize that in a dynamic reaching environment, where subjects have to hit moving targets and the targets' dynamic characteristics affect task success, implicit processes will benefit from target errors as well. We examine the effect of target errors on learning of an unnoticed perturbation during unconstrained reaching movements. Subjects played a Pong game, in which they had to hit a moving ball by moving a paddle controlled by their hand. During the game, the movement of the paddle was gradually rotated with respect to the hand, reaching a final rotation of 25°. Subjects were assigned to one of two groups: The high-target error group played the Pong with a small ball, and the low-target error group played with a big ball. Before and after the Pong game, subjects performed open-loop reaching movements toward static targets with no visual feedback. While both groups adapted to the rotation, the postrotation reaching movements were directionally biased only in the small-ball group. This result provides evidence that implicit adaptation is sensitive to target errors. Copyright © 2016 the American Physiological Society.

  20. ELECTROMAGNETIC APPARATUS FOR MOVING A ROD

    Science.gov (United States)

    Young, J.N.

    1958-04-22

    An electromagnetic apparatus for moving a rod-like member in small steps in either direction is described. The invention has particular application in the reactor field where the reactor control rods must be moved only a small distance and where the use of mechanical couplings is impractical due to the high- pressure seals required. A neutron-absorbing rod is mounted in a housing with gripping uaits that engage the rod, and coils for magnetizing the gripping units to make them grip, shift, and release the rod are located outside the housing.

  1. Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

    Science.gov (United States)

    Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

    2017-05-01

    Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  2. Moving a House by Moved Participants

    DEFF Research Database (Denmark)

    Axel, Erik

    himself in controlling every detail of the shape of the concrete slaps. He pushed all the other participants of the meetings, asking for details, information, the change of drawings etc. He explained the technical issues he was pursuing, was prepared for problems at the meetings, was well informed, always......? The participant observer believed it was a matter of changing coordinates, but the engineers immediately saw it was an issue of pipes in the ground, could they be moved and still function as planned? To decide the possibility of this suggestion the engineer was given the task of investigating the consequences...... they saw him as a bit pushy. On the other hand they understood why he was so since his firm would be fined if the concrete slabs did not meet specifications. The case will be the basis for a discussion of double motivation of the engineer, his evident interest in his professional work, and the wish...

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

    Directory of Open Access Journals (Sweden)

    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

  4. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

    Science.gov (United States)

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-02-25

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody (99m)Tc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm(3) ± 21.2 and 26.6 mm(3) ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of (99m)Tc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody (99m)Tc-D10.

  5. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

    Science.gov (United States)

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-01-01

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

  6. Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR-targeted chitosan nanoparticles.

    Science.gov (United States)

    Nascimento, Ana Vanessa; Singh, Amit; Bousbaa, Hassan; Ferreira, Domingos; Sarmento, Bruno; Amiji, Mansoor M

    2017-01-01

    Efficiency of chemotherapy is often limited by low therapeutic index of the drug as well as emergence of inherent and acquired drug resistance in cancer cells. As a common strategy to overcome drug resistance, higher doses of chemo-agents are administered. However, adverse side effects are usually increased as a consequence. A potentially effective approach is to combine chemotherapy with other therapeutic strategies such as small interfering RNAs (siRNAs) that allow the use of lower yet efficient doses of the anticancer drugs. We previously developed epidermal growth factor receptor (EGFR)-targeted chitosan (CS) nanoparticles as a versatile delivery system for silencing the essential mitotic checkpoint gene Mad2, and induce cell death. Here, we tested this system as a single therapy and in combination with cisplatin in cisplatin sensitive and resistant lung cancer models, and characterized its in vivo efficacy and safety. Combination treatment resulted in significant improvement in tumor inhibition that was strikingly more effective in cisplatin-resistant tumors. Importantly, effective cisplatin dosage was dramatically reduced in the co-therapy regimen resulting in negligible toxic effects from the drug as confirmed by parameters such as body weight gain, biochemical markers of hepatic and renal function, and histopathology of liver/kidney/spleen tissues. Overall, we demonstrate that the combination of Mad2 siRNA-loaded CS nanoparticles strategy with chemotherapeutic agents such as cisplatin constitutes an efficient and safe approach for the treatment of drug resistant tumors. Lung cancer remains one of the leading killers in the United States and around the world. Platinum agents, including cisplatin, are the first line treatment in lung cancer, including non-small cell lung cancer (NSCLC), which is the predominant form of lung cancer. In this study, we have evaluated Mad2 cell-cycle checkpoint gene silencing using small interfering RNA (siRNA) delivered

  7. Heavy water jet target and a beryllium target for production of fast neutrons

    International Nuclear Information System (INIS)

    Logan, C.M.; Anderson, J.D.; Barschall, H.H.; Davis, J.C.

    1975-01-01

    A limitation on the neutron flux obtainable from proton or deuteron induced reactions is the heating of the target by the accelerated charged particles. The heat can be removed more easily if the target moves. The possibility of using a rotating Be target and a heavy water jet as a target for bombardment by 35-MeV deuterons was studied. In a thick Be metal target moving at 10 m/sec through such a beam of 1 cm diameter a temperature pulse of about 300 0 C will be produced by the 0.3 MW beam. The Be target should be able to withstand such a temperature pulse. A Be target suitable for 3 MW of power in a 1 cm diameter beam would require internal cooling and a higher velocity. A free jet of heavy water is also a possible target. Laser photographs of water jets in vacuum show small angles of divergence. The effect of heating by a 0.3 MW beam is probably not important because the temperature rise produced by the beam is small compared to the absolute temperature of the unheated jet. (auth)

  8. MOVES regional level sensitivity analysis

    Science.gov (United States)

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  9. Move of ground water

    International Nuclear Information System (INIS)

    Kimura, Shigehiko

    1983-01-01

    As a ground water flow which is difficult to explain by Darcy's theory, there is stagnant water in strata, which moves by pumping and leads to land subsidence. This is now a major problem in Japan. Such move on an extensive scale has been investigated in detail by means of 3 H such as from rainfall in addition to ordinary measurement. The move of ground water is divided broadly into that in an unsaturated stratum from ground surface to water-table and that in a saturated stratum below the water-table. The course of the analyses made so far by 3 H contained in water, and the future trend of its usage are described. A flow model of regarding water as plastic fluid and its flow as channel assembly may be available for some flow mechanism which is not possible to explain with Darcy's theory. (Mori, K.)

  10. Moving to Jobs?

    OpenAIRE

    Dave Maré; Jason Timmins

    2003-01-01

    This paper examines whether New Zealand residents move from low-growth to high-growth regions, using New Zealand census data from the past three inter-censal periods (covering 1986-2001). We focus on the relationship between employment growth and migration flows to gauge the strength of the relationship and the stability of the relationship over the business cycle. We find that people move to areas of high employment growth, but that the probability of leaving a region is less strongly relate...

  11. Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

    Science.gov (United States)

    Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

    2016-11-01

    Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

  12. Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    So-Young Hwang

    2016-06-01

    Full Text Available The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic β-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF-dependent luciferase-reporter system, we screened for small-molecule compounds that act against Wnt/β-catenin signaling and identified MSAB (methyl 3-{[(4-methylphenylsulfonyl]amino}benzoate as a selective inhibitor of Wnt/β-catenin signaling. MSAB shows potent anti-tumor effects selectively on Wnt-dependent cancer cells in vitro and in mouse cancer models. MSAB binds to β-catenin, promoting its degradation, and specifically downregulates Wnt/β-catenin target genes. Our findings might represent an effective therapeutic strategy for cancers addicted to the Wnt/β-catenin signaling pathway.

  13. The impact of time between staging PET/CT and definitive chemo-radiation on target volumes and survival in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Everitt, Sarah; Plumridge, Nikki; Herschtal, Alan; Bressel, Mathias; Ball, David; Callahan, Jason; Kron, Tomas; Schneider-Kolsky, Michal; Binns, David; Hicks, Rodney J.

    2013-01-01

    Background and purpose: To investigate the impact of treatment delays on radiation therapy (RT) target volumes and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who underwent two baseline FDG PET/CT scans. Material and methods: Patients underwent a staging (PET1) and RT planning (PET2) FDG PET/CT scan. At PET1 all patients were eligible for radical chemo-RT. OS and progression-free survival (PFS) were compared for patients remaining eligible for radical RT and those treated palliatively because PET2 showed progression. RT target volumes were contoured using PET1 and PET2. Normal tissue doses were compared for patients remaining eligible for radical RT. Results: Eighty-two patients underwent PET2 scans between October 2004 and February 2007. Of these, 21 had a prior PET1 scan, median 23 days apart (range 8–176 days). Six patients (29%) were unsuitable for radical RT after PET2; five received palliative treatment and one received no treatment. Patients treated palliatively had significantly worse OS and PFS than patients treated radically p < 0.001. Mean RT tumour volume increased from 105cc to 198cc (p < 0.005) between scans. Conclusions: Disease progression while awaiting initiation of curative RT in NSCLC is associated with larger treatment volumes and worse survival

  14. Structure-based development of small molecule PFKFB3 inhibitors: a framework for potential cancer therapeutic agents targeting the Warburg effect.

    Directory of Open Access Journals (Sweden)

    Minsuh Seo

    Full Text Available Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 Å resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.

  15. Deep sequencing of Salmonella RNA associated with heterologous Hfq proteins in vivo reveals small RNAs as a major target class and identifies RNA processing phenotypes.

    Science.gov (United States)

    Sittka, Alexandra; Sharma, Cynthia M; Rolle, Katarzyna; Vogel, Jörg

    2009-01-01

    The bacterial Sm-like protein, Hfq, is a key factor for the stability and function of small non-coding RNAs (sRNAs) in Escherichia coli. Homologues of this protein have been predicted in many distantly related organisms yet their functional conservation as sRNA-binding proteins has not entirely been clear. To address this, we expressed in Salmonella the Hfq proteins of two eubacteria (Neisseria meningitides, Aquifex aeolicus) and an archaeon (Methanocaldococcus jannaschii), and analyzed the associated RNA by deep sequencing. This in vivo approach identified endogenous Salmonella sRNAs as a major target of the foreign Hfq proteins. New Salmonella sRNA species were also identified, and some of these accumulated specifically in the presence of a foreign Hfq protein. In addition, we observed specific RNA processing defects, e.g., suppression of precursor processing of SraH sRNA by Methanocaldococcus Hfq, or aberrant accumulation of extracytoplasmic target mRNAs of the Salmonella GcvB, MicA or RybB sRNAs. Taken together, our study provides evidence of a conserved inherent sRNA-binding property of Hfq, which may facilitate the lateral transmission of regulatory sRNAs among distantly related species. It also suggests that the expression of heterologous RNA-binding proteins combined with deep sequencing analysis of RNA ligands can be used as a molecular tool to dissect individual steps of RNA metabolism in vivo.

  16. Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Hongxin Cao

    Full Text Available Small cell lung cancer (SCLC is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.

  17. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    CERN Document Server

    Magro, G; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M

    2015-01-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5–30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size r...

  18. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  19. Design of a Bioactive Small Molecule that Targets the Myotonic Dystrophy Type 1 RNA Via an RNA Motif-Ligand Database & Chemical Similarity Searching

    Science.gov (United States)

    Parkesh, Raman; Childs-Disney, Jessica L.; Nakamori, Masayuki; Kumar, Amit; Wang, Eric; Wang, Thomas; Hoskins, Jason; Tran, Tuan; Housman, David; Thornton, Charles A.; Disney, Matthew D.

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5′CUG/3′GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, Sarco(endo)plasmic reticulum Ca2+ ATPase 1 (Serca1/Atp2a1), and cardiac troponin T (cTNT). Based on these observations, the development of small molecule ligands that target specifically expanded DM1 repeats could serve as therapeutics. In the present study, computational screening was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of inhibitors of the RNA-protein complex with low micromolar IC50’s, which are >20-fold more potent than the query compounds, were identified. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with virtual screening. PMID:22300544

  20. Variations in Target Volume Definition for Postoperative Radiotherapy in Stage III Non-Small-Cell Lung Cancer: Analysis of an International Contouring Study

    International Nuclear Information System (INIS)

    Spoelstra, Femke; Senan, Suresh; Le Pechoux, Cecile; Ishikura, Satoshi; Casas, Francesc; Ball, David; Price, Allan; De Ruysscher, Dirk; Soernsen de Koste, John R. van

    2010-01-01

    Purpose: Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). Methods and Materials: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. Results: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V 20 values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. Conclusion: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.